Full text of "Robert Whitaker - Anatomy Of An Epidemic

Full text of "Robert Whitaker - Anatomy Of An Epidemic: Magic Bullets, Psychiatric Drugs, And The Astonishing Rise Of Mental Illness In America"

“lucid, pointed, and important, Anatomy of tin Epidemic should be required reading lor anyone

considering extended use ol psychiatric medicine. Whitaker is at the height ol his powers.”

— Greg Critser, author oe Generation Rx

ANATOMY OF AN EPIDEMIC

Magic Bullets, Psychiatric Drugs, and the

Astonishing Rise of Mental Illness in America

ROBERT WHITAKER

Author of Mad in America

$26.00

(Canada: $32.00)

I n this astonishing and startling book, award¬

winning science and history writer Robert Whita¬

ker investigates a medical mystery: Why has the

number of disabled mentally ill in the United States

tripled over the past two decades? Every day 1,100

adults and children are added to the government dis¬

ability rolls because they have become newly disabled

by mental illness, with this epidemic spreading most

rapidly among our nation's children. What is going on?

Anatomy of an Epidemic challenges readers to think

through that question themselves. First, Whitaker

investigates what is known today about the biological

causes of mental disorders. Do psychiatric medications

fix "chemical imbalances" in the brain, or do they, in

fact, create them? Researchers spent decades studying

that question, and by the late 1980s, they had their

answer. Readers will be startled—and dismayed—to

discover what was reported in the scientific journals.

Then comes the scientific query at the heart of

this book: During the past fifty years, when investi¬

gators looked at how psychiatric drugs affected long¬

term outcomes, what did they find? Did they discover

that the drugs help people stay well? Function better?

Enjoy good physical health? Or did they find that these

medications, for some paradoxical reason, increase the

likelihood that people will become chronically ill, less

able to function well, more prone to physical illness?

This is the first book to look at the merits of psy¬

chiatric medications through the prism oflong-term

results. Are long-term recovery rates higher for medi¬

cated or unmedicated schizophrenia patients? Does

taking an antidepressant decrease or increase the risk

that a depressed person will become disabled by the

disorder? Do bipolar patients fare better today than

they did forty years ago, or much worse? When the

National Institute ofMental Health (NIMH) studied

the long-term outcomes of children with ADHD, did

they determine that stimulants provide any benefit?

By the end of this review of the outcomes lit¬

erature, readers are certain to have a haunting

question of their own: Why have the results from these

(continued on back flap)

Also by Robert Whitaker

Mad in America

The Maptnaker's Wife

On the Laps of Gods

ANATOMY OF AN EPIDEMIC

Magic Bullets,

Psychiatric Drugs,

and the

Astonishing Rise of

Mental Illness

in America

Robert Whitaker

CROWN PUBLISHERS

New York

Published in the United States by Crown Publishers, an imprint of the Crown Publishing

Group, a division of Random House, Inc., New York.

www.crownpublishing.com

CROWN and the Crown colophon are registered trademarks of Random House, Inc.

Library of Congress Cataloging-in-Publication Data

Whitaker, Robert.

Anatomy of an epidemic : magic bullets, psychiatric drugs, and the astonishing rise of

mental illness in America / Robert Whitaker,

p. ; cm.

Includes bibliographical references and index.

1. Mental illness—United States. 2. Psychotropic drugs —Prescribing —United States.

3. Psychiatry —United States. I. Title.

[DNLM: 1. Psychiatry—ethics —United States. 2. Psychiatry —history —United States.

3. Mental Disorders —drug therapy —United States. 4. Mental Disorders —

epidemiology —United States. WM 11 AA1 W578a 2010]

RC443.W437 2010

616.89 —dc22 2009049467

ISBN 978-0-307-45241-2

Printed in the United States of America

Illustrations by Hadel Studio, Westbury NY

10 987654321

First Edition

To Lindsay

May you sing "Seasons of Love" again

and be filled with joy

CONTENTS

Foreword • ix

Part One: The Epidemic

i. A Modern Plague • 3

2. Anecdotal Thoughts • 12

Part Two: The Science of Psychiatric Drugs

3 . The Roots of an Epidemic *39

4. Psychiatry's Magic Bullets *47

5. The Hunt for Chemical Imbalances • 67

Part Three: Outcomes

6 . A Paradox Revealed • 89

7. The Benzo Trap *126

8. An Episodic Illness Turns Chronic • 148

9 . The Bipolar Boom • 1 72

10. An Epidemic Explained • 20 $

V i i i . CONTENTS

ii. The Epidemic Spreads to Children 216

12. Suffer the Children 247

Part Four: Explication of a Delusion

13. The Rise of an Ideology 263

14. The Story That Was ... and Wasn't Told 283

15. Tallying Up the Profits 313

Part Five: Solutions

16. Blueprints for Reform 331

Epilogue 361

Notes 363

Acknowledgments 3 9 5

Index 397

FOREWORD

The history of psychiatry and its treatments can be a contentious

issue in our society, so much so that when you write about it, as I

did in an earlier book, Mad in America, people regularly ask about

how you became interested in the subject. The assumption is that

you must have a personal reason for being curious about this topic,

as otherwise you would want to stay away from what can be such a

political minefield. In addition, the person asking the question is

often trying to determine if you have any personal bias that colors

your writing.

In my case, I had no personal attachment to the subject at all. I

came to it in a very back-door manner.

In 1994, after having worked a number of years as a newspaper

reporter, I left daily journalism to cofound a publishing company,

CenterWatch, that reported on the business aspects of the clinical

testing of new drugs. Our readers came from pharmaceutical com¬

panies, medical schools, private medical practices, and Wall Street,

and for the most part, we wrote about this enterprise in an industry-

friendly way. We viewed clinical trials as part of a process that

brought improved medical treatments to market, and we reported

on the financial aspects of that growing industry. Then, in early

1998, I stumbled upon a story that told of the abuse of psychiatric

FOREWORD

patients in research settings. Even while I co-owned CenterWatch, I

occasionally wrote freelance articles for magazines and newspapers,

and that fall I cowrote a series on this problem for the Boston

Globe.

There were several types of "abuses” that Dolores Kong and I

focused on. We looked at studies funded by the National Institute of

Mental Health (NIMH) that involved giving schizophrenia patients

a drug designed to exacerbate their symptoms (the studies were

probing the biology of psychosis). We investigated the deaths that

had occurred during the testing of the new atypical antipsychotics.

Finally, we reported on studies that involved withdrawing schizo¬

phrenia patients from their antipsychotic medications, which we

figured was an unethical thing to do. In fact, we thought it was out¬

rageous.

Our reasoning was easy to understand. These drugs were said to

be like "insulin for diabetes.” I had known that to be "true” for

some time, ever since I had covered the medical beat at the Albany

Times Union. Clearly, then, it was abusive for psychiatric re¬

searchers to have run dozens of withdrawal studies in which they

carefully tallied up the percentage of schizophrenia patients who be¬

came sick again and had to be rehospitalized. Would anyone ever

conduct a study that involved withdrawing insulin from diabetics to

see how fast they became sick again?

That's how we framed the withdrawal studies in our series, and

that would have been the end of my writing on psychiatry except

for the fact that I was left with an unresolved question, one that

nagged at me. While reporting that series, I had come upon two re¬

search findings that just didn't make sense. The first was by Har¬

vard Medical School investigators, who in 1994 announced that

outcomes for schizophrenia patients in the United States had wors¬

ened during the past two decades and were now no better than they

had been a century earlier. The second was by the World Health Or¬

ganization, which had twice found that schizophrenia outcomes

were much better in poor countries, like India and Nigeria, than in

the United States and other rich countries. I interviewed various ex¬

perts about the WHO findings, and they suggested that the poor

outcomes in the United States were due to social policies and cul-

FOREWORD

tural values. In the poor countries, families were more supportive of

those with schizophrenia, they said. Although this seemed plausible,

it wasn't an altogether satisfactory explanation, and after the series

ran in the Boston Globe, I went back and read all of the scientific

articles related to the WHO study on schizophrenia outcomes. It

was then that I learned of this startling fact: In the poor countries,

only 16 percent of patients were regularly maintained on anti¬

psychotic medications.

That is the story of my entry into the psychiatry "minefield.” I

had just cowritten a series that had focused, in one of its parts, on

how unethical it was to withdraw schizophrenia patients from their

medications, and yet here was a study by the World Health Orga¬

nization that seemingly had found an association between good

outcomes and not staying continuously on the drugs. I wrote Mad

in America, which turned into a history of our country's treatment

of the severely mentally ill, to try to understand how that could be.

I confess all this for a simple reason. Since psychiatry is such a

controversial topic, I think it is important that readers understand

that I began this long intellectual journey as a believer in the con¬

ventional wisdom. I believed that psychiatric researchers were dis¬

covering the biological causes of mental illnesses and that this

knowledge had led to the development of a new generation of

psychiatric drugs that helped "balance” brain chemistry. These

medications were like "insulin for diabetes.” I believed that to be

true because that is what I had been told by psychiatrists while writ¬

ing for newspapers. But then I stumbled upon the Harvard study

and the WHO findings, and that set me off on an intellectual quest

that ultimately grew into this book, Anatomy of an Epidemic.

Part One

The Epidemic

A Modern Plague

'That is the essence of science: ask an impertinent

question, and you are on the way to

a pertinent answer."

-JACOB BRONOWSKI ( 1973 )'

This is the story of a medical puzzle. The puzzle is of a most curious

sort, and yet one that we as a society desperately need to solve, for

it tells of a hidden epidemic that is diminishing the lives of millions

of Americans, including a rapidly increasing number of children. The

epidemic has grown in size and scope over the past five decades, and

now disables 850 adults and 250 children every day. And those star¬

tling numbers only hint at the true scope of this modern plague, for

they are only a count of those who have become so ill that their

families or caregivers are newly eligible to receive a disability check

from the federal government.

Now, here is the puzzle.

As a society, we have come to understand that psychiatry has made

great progress in treating mental illness over the past fifty years. Scien¬

tists are uncovering the biological causes of mental disorders, and

pharmaceutical companies have developed a number of effective med¬

ications for these conditions. This story has been told in newspapers,

magazines, and books, and evidence of our societal belief in it can be

found in our spending habits. In 2007, we spent $25 billion on anti¬

depressants and antipsychotics, and to put that figure in perspective,

that was more than the gross domestic product of Cameroon, a nation

of 18 million people. 2

ANATOMY OF AN EPIDEMIC

In 1999, U.S. surgeon general David Satcher neatly summed up

this story of scientific progress in a 458-page report titled Mental

Health. The modern era of psychiatry, he explained, could be said

to have begun in 1954. Prior to that time, psychiatry lacked treat¬

ments that could "prevent patients from becoming chronically ill."

But then Thorazine was introduced. This was the first drug that was

a specific antidote to a mental disorder —it was an antipsychotic

medication —and it kicked off a psychopharmacological revolution.

Soon antidepressants and antianxiety agents were discovered,

and as a result, today we enjoy "a variety of treatments of well-

documented efficacy for the array of clearly defined mental and be¬

havioral disorders that occur across the life span," Satcher wrote.

The introduction of Prozac and other "second-generation" psychi¬

atric drugs, the surgeon general added, was "stoked by advances in

both neurosciences and molecular biology" and represented yet an¬

other leap forward in the treatment of mental disorders. 3

Medical students training to be psychiatrists read about this his¬

tory in their textbooks, and the public reads about it in popular

accounts of the field. Thorazine, wrote University of Toronto pro¬

fessor Edward Shorter, in his 1997 book, A History of Psychiatry,

"initiated a revolution in psychiatry, comparable to the introduc¬

tion of penicillin in general medicine." 4 That was the start of the

"psychopharmacology era," and today we can rest assured that sci¬

ence has proved that the drugs in psychiatry's medicine cabinet are

beneficial. "We have very effective and safe treatments for a broad

array of psychiatric disorders,” Richard Friedman, director of the

psychopharmacology clinic at Weill Cornell Medical College, in¬

formed readers of the New York Times on June 19, 2007. 5 Three

days later, the Boston Globe, in an editorial titled "When Kids Need

Meds," echoed this sentiment: "The development of powerful drugs

has revolutionized the treatment of mental illness." 6

Psychiatrists working in countries around the world also under¬

stand this to be true. At the 161st annual meeting of the American

Psychiatric Association, which was held in May 2008 in Washington,

D.C., nearly half of the twenty thousand psychiatrists who attended

were foreigners. The hallways were filled with chatter about schizo¬

phrenia, bipolar illness, depression, panic disorder, attention deficit/

A MODERN PLAGUE

hyperactivity disorder, and a host of other conditions described in

the APA's Diagnostic and Statistical Manual of Mental Disorders,

and over the course of five days, most of the lectures, workshops,

and symposiums told of advances in the field. "We have come a

long way in understanding psychiatric disorders, and our knowl¬

edge continues to expand,” APA president Carolyn Robinowitz told

the audience in her opening-day address. "Our work saves and

improves so many lives." 7

But here is the conundrum. Given this great advance in care, we

should expect that the number of disabled mentally ill in the United

States, on a per-capita basis, would have declined over the past fifty

years. We should also expect that the number of disabled mentally

ill, on a per-capita basis, would have declined since the arrival in

1988 of Prozac and the other second-generation psychiatric drugs.

We should see a two-step drop in disability rates. Instead, as the

psychopharmacology revolution has unfolded, the number of dis¬

abled mentally ill in the United States has skyrocketed. Moreover,

this increase in the number of disabled mentally ill has accelerated

further since the introduction of Prozac and the other second-

generation psychiatric drugs. Most disturbing of all, this modern-

day plague has now spread to the nation's children.

The disability numbers, in turn, lead to a much larger question.

Why are so many Americans today, while they may not be disabled

by mental illness, nevertheless plagued by chronic mental problems —

by recurrent depression, by bipolar symptoms, and by crippling

anxiety? If we have treatments that effectively address these disor¬

ders, why has mental illness become an ever-greater health problem

in the United States?

The Epidemic

Now, I promise that this will not just be a book of statistics. We are

trying to solve a mystery in this book, and this will lead to an ex¬

ploration of science and history, and ultimately to a story with

many surprising twists. But this mystery arises from an in-depth

ANATOMY OF AN EPIDEMIC

analysis of government statistics, and so, as a first step, we need to

track the disability numbers over the past fifty years to make certain

that the epidemic is real.

In 1955, the disabled mentally ill were primarily cared for in state

and county mental hospitals. Today, they typically receive either a

monthly Supplemental Security Income (SSI) or Social Security

Disability Insurance (SSDI) payment, and many live in residential

shelters or other subsidized living arrangements. Both statistics pro¬

vide a rough count of the number of people under governmental

care because they have been disabled by mental illness.

In 1955, there were 566,000 people in state and county mental

hospitals. However, only 355,000 had a psychiatric diagnosis, as

the rest suffered from alcoholism, syphilis-related dementia, Alz-

The Hospitalized Mentally III in 1955

First Admissions

Resident Patients

Psychotic Disorders

Schizophrenia

28,482

267,603

Manic-depressive

9,679

50,937

Other

1,387

1 4,734

Psychoneurosis (Anxiety)

6,549

5,41 5

Personality Disorders

8,730

9,739

All Others

6,497

6,966

Although there were 558,922 resident patients in state and county mental hospitals in 1 955,

only 355,000 suffered from mental illness. The other 200,000 were elderly patients suffering from

dementia, end-stage syphilis, alcoholism, mental retardation, and various neurological syn¬

dromes. Source: Silverman, C. The Epidemiology of Depression (1 968): 1 39.

heimer's, and mental retardation, a population that would not show

up in a count of the disabled mentally ill today. 8 Thus, in 1955, 1 in

every 468 Americans was hospitalized due to a mental illness. In

1987, there were 1.25 million people receiving an SSI or SSDI pay¬

ment because they were disabled by mental illness, or 1 in every 184

Americans.

A MODERN PLAGUE

Now it may be argued that this is an apples-to-oranges com¬

parison. In 1955, societal taboos about mental illness may have led

to a reluctance to seek treatment, and thus to low hospitalization

rates. It's also possible that a person had to be sicker to get hos¬

pitalized in 1955 than to receive SSI or SSDI in 1987, and that's why

the 1987 disability rate is so much higher. However, arguments can

be made in the other direction, too. The SSI and SSDI numbers only

provide a count of the disabled mentally ill less than sixty-five years

old, whereas the mental hospitals in 1955 were home to many el¬

derly schizophrenics. There were also many more mentally ill people

who were homeless and in jail in 1987 than in 1955, and that pop¬

ulation doesn't show up in the disability numbers. The comparison

is an imperfect one, but it's the best one we can make to track dis¬

ability rates between 1955 and 1987.

Fortunately, from 1987 forward it's an apples-to-apples compar¬

ison, involving only the SSI and SSDI numbers. The Food and Drug

Administration approved Prozac in 1987, and over the next two

decades the number of disabled mentally ill on the SSI and SSDI

rolls soared to 3.97 million. 9 In 2007, the disability rate was 1 in

every 76 Americans. That's more than double the rate in 1987, and

six times the rate in 1955. The apples-to-apples comparison proves

that something is amiss.

If we drill down into the disability data a bit more, we find a sec¬

ond puzzle. In 1955, major depression and bipolar illness didn't

disable many people. There were only 50,937 people in state and

county mental hospitals with a diagnosis for one of those affective

disorders. 10 But during the 1990s, people struggling with depression

and bipolar illness began showing up on the SSI and SSDI rolls in

ever-increasing numbers, and today there are an estimated 1.4 mil¬

lion people eighteen to sixty-four years old receiving a federal

payment because they are disabled by an affective disorder." More¬

over, this trend is accelerating: According to a 2008 report by the

U.S. General Accountability Office, 46 percent of the young adults

(ages eighteen to twenty-six) who received an SSI or SSDI payment

because of a psychiatric disability in 2006 were diagnosed with an

affective illness (and another 8 percent were disabled by "anxiety

disorder"). 12

ANATOMY OF AN EPIDEMIC

The Disabled Mentally III in the Prozac Era

SSI and SSDI Recipients Under Age 65 Disabled by Mental Illness, 1987-2007

One in every six SSDI recipients also receives an SSI payment; thus the total number of recipients

is less than the sum ofthe SSI and SSDI numbers. Source: Social Security Administration reports,

1 987-2007.

This plague of disabling mental illness has now spread to our

children, too. In 1987, there were 16,200 children under eighteen

years of age who received an SSI payment because they were dis¬

abled by a serious mental illness. Such children comprised only 5.5

percent of the 293,000 children on the disability rolls —mental ill¬

ness was not, at that time, a leading cause of disability among the

country's children. But starting in 1990, the number of mentally ill

children began to rise dramatically, and by the end of 2007, there

were 561,569 such children on the SSI disability rolls. In the short

span of twenty years, the number of disabled mentally ill children

rose thirty-five fold. Mental illness is now the leading cause of dis¬

ability in children, with the mentally ill group comprising 50 per¬

cent of the total number of children on the SSI rolls in 2007. 13

The baffling nature of this childhood epidemic shows up with

particular clarity in the SSI data from 1996 to 2007. Whereas the

number of children disabled by mental illness more than doubled

during this period, the number of children on the SSI rolls for all

other reasons —cancers, retardation, etc . — declined, from 728,110

A MODERN PLAGUE

to 559,448. The nation's doctors were apparently making progress

in treating all of those other conditions, but when it came to mental

disorders, just the opposite was true.

A Scientific Inquiry

The puzzle can now be precisely summed up. On the one hand, we

know that many people are helped by psychiatric medications.

We know that many people stabilize well on them and will person¬

ally attest to how the drugs have helped them lead normal lives.

Furthermore, as Satcher noted in his 1999 report, the scientific liter¬

ature does document that psychiatric medications, at least over the

short term, are "effective.” Psychiatrists and other physicians who

prescribe the drugs will attest to that fact, and many parents of chil¬

dren taking psychiatric drugs will swear by the drugs as well. All of

that makes for a powerful consensus: Psychiatric drugs work and

help people lead relatively normal lives. And yet, at the same time,

we are stuck with these disturbing facts: The number of disabled

mentally ill has risen dramatically since 1955, and during the past

two decades, a period when the prescribing of psychiatric medica¬

tions has exploded, the number of adults and children disabled by

mental illness has risen at a mind-boggling rate. Thus we arrive at

an obvious question, even though it is heretical in kind: Could our

drug-based paradigm of care, in some unforeseen way, be fueling

this modern-day plague?

My hope is that Anatomy of an Epidemic will serve as an explor¬

ation of that question. It's also easy to see what we must find if we

are to solve this puzzle. We will need to discover a history of science

that unfolds over the course of fifty-five years, arises from the very

best research, and explains all aspects of our puzzle. The history

must reveal why there has been a dramatic increase in the number

of disabled mentally ill, it must explain why disabling affective dis¬

orders are so much more common now than they were fifty years

ago, and it must explain why so many children are being laid low by

serious mental illness today. And if we find such a history, we

ANATOMY OF AN EPIDEMIC

l o

should then be able to explain why it has remained hidden and

unknown.

It's also easy to see what is at stake here. The disability numbers

only hint at the extraordinary toll that mental illness is exacting on

our society. The GAO, in its June 2008 report, concluded that one

in every sixteen young adults in the United States is now "seriously

mentally ill." There has never been a society that has seen such a

plague of mental illness in its newly minted adults, and those who

go on the SSI and SSDI rolls at this young age are likely to spend the

rest of their lives receiving disability payments. The twenty-year-old

who goes on SSI or SSDI will receive more than $1 million in bene¬

fits over the next forty or so years, and that is a cost —should this

epidemic continue to grow —that our society will not be able to

afford.

There is one other, subtler aspect to this epidemic. Over the past

twenty-five years, psychiatry has profoundly reshaped our society.

Through its Diagnostic and Statistical Manual, psychiatry draws a

line between what is "normal" and what is not. Our societal under¬

standing of the human mind, which in the past arose from a medley

of sources (great works of fiction, scientific investigations, and

philosophical and religious writings), is now filtered through the

DSM. Indeed, the stories told by psychiatry about "chemical imbal¬

ances" in the brain have reshaped our understanding of how the

mind works and challenged our conceptions of free will. Are we

really the prisoners of our neurotransmitters? Most important, our

children are the first in human history to grow up under the con¬

stant shadow of "mental illness.” Not too long ago, goof-offs, cut¬

ups, bullies, nerds, shy kids, teachers' pets, and any number of other

recognizable types filled the schoolyard, and all were considered

more or less normal. Nobody really knew what to expect from such

children as adults. That was part of the glorious uncertainty of life —

the goof-off in the fifth grade might show up at his high school's

twenty-year reunion as a wealthy entrepreneur, the shy girl as an

accomplished actress. But today, children diagnosed with mental

disorders —most notably, ADHD, depression, and bipolar illness-

help populate the schoolyard. These children have been told that

they have something wrong with their brains and that they may

A MODERN PLAGUE

have to take psychiatric medications the rest of their lives, just like a

"diabetic takes insulin.” That medical dictum teaches all of the chil¬

dren on the playground a lesson about the nature of humankind,

and that lesson differs in a radical way from what children used to

be taught.

So here is what is at stake in this investigation: If the conven¬

tional history is true, and psychiatry has in fact made great progress

in identifying the biological causes of mental disorders and in devel¬

oping effective treatments for those illnesses, then we can conclude

that psychiatry's reshaping of our society has been for the good. As

bad as the epidemic of disabling mental illness may be, it is reason¬

able to assume that without such advances in psychiatry, it would

be much worse. The scientific literature will show that millions of

children and adults are being helped by psychiatric medications,

their lives made richer and fuller, just as APA president Carolyn

Robinowitz said in her speech at the APA's 2008 convention. But if

we uncover a history of a different sort —a history that shows that

the biological causes of mental disorders remain to be discovered

and that psychiatric drugs are in fact fueling the epidemic of dis¬

abling mental illness what then? We will have documented a his¬

tory that tells of a society led horribly astray and, one might say,

betrayed.

And if that is so, we will spend the final part of this book looking

at what we, as a society, might do to forge a different future.

Anecdotal Thoughts

"If we value the pursuit of knowledge, we must he

free to follow wherever that search may lead us."

— ADLAI STEVENSON ( 1952 )'

McLean Hospital in Belmont, Massachusetts, is one of the oldest

mental hospitals in the United States, as it was founded in 1817,

when a type of care known as moral therapy was being popularized

by Quakers. Their belief was that a retreat for the mentally ill

should be built in a pastoral setting, and even today the McLean

campus, with its handsome brick buildings and shaded lawns, feels

like an oasis. On the evening in August 2008 that I came there, in

order to attend a meeting of the Depression and Bipolar Support Al¬

liance, that sense of tranquility was heightened by the weather. It

was one of the most gorgeous nights of the summer, and as I ap¬

proached the cafeteria where the meeting was to be held, I figured

that attendance that night would be sparse. It was just too nice of a

night to be inside. This was a meeting for people living in the com¬

munity, which meant they would have to leave their homes and

apartments to come here, and given that the McLean group met five

times a week —there was an afternoon session every Monday, Thurs¬

day, Friday, and Saturday, and an evening meeting every Wednes¬

day—I reasoned that most people attached to the group would skip

this one.

I was wrong.

There were a hundred or so people filling the cafeteria, a scene

ANECDOTAL THOUGHTS

that, in a small way, bore witness to the epidemic of disabling men¬

tal illness that has erupted in our country over the past twenty

years. The Depression and Bipolar Support Alliance (DBSA) was

founded in 1985 (known initially as the Depressive and Manic-

Depressive Association), with this group at McLean starting up

shortly after that, and today the organization counts nearly one

thousand of its support groups nationwide. There are seven such

groups in the Greater Boston area alone, and most —like the group

that meets at McLean —offer people a chance to get together and

talk several times a week. The DBSA has grown in lockstep with the

epidemic.

The first hour of the meeting was given over to a talk about

"flotation therapy," and at first glance, the audience was really not

identifiable —at least not by an outsider such as myself —as a patient

group. The people here ranged widely in age, the youngest in their

late teens and the oldest in their sixties, and although the women

outnumbered the men, this gender disparity might have been ex¬

pected, given that depression affects more women than men. Most

in the audience were white, which perhaps reflected the fact that

Belmont is an affluent town. Perhaps the one telltale sign that the

meeting was for people diagnosed with a mental illness was that a

fair number were overweight. People diagnosed with bipolar disor¬

der are often prescribed an atypical antipsychotic, such as Zyprexa,

and those drugs regularly cause people to put on the pounds.

After the talk ended, Steve Lappen, one of the DBSA leaders in

Boston, listed the various groups that would now meet. There was

one for "newcomers," another for "family and friends," a third for

"young adults," a fourth for "maintaining stability,” and so on,

with the last of the eight choices an "observer's group,” which Steve

had organized for me.

There were nine in our group (excluding myself), and by way of

introduction, everyone briefly spoke about how he or she had

been doing lately — "I've been having a hard time” was a common

refrain —and told of his or her specific diagnosis. The man to my

right was a former executive who had lost his job because of his

recurring depression, and as we went around the room, such life

stories spilled out. A younger woman told of a troubled marriage to

ANATOMY OF AN EPIDEMIC

a Chinese man who, because of his culture, didn't like to talk about

mental illness. Next to her, a former prosecuting attorney spoke of

how he'd lost his wife two years ago, and since then "I don't feel

like I know who I am.” A woman who was an adjunct professor at

an area college told of how difficult her work was at the moment,

and finally, a nurse who had been recently hospitalized at McLean

for depression explained what drove her to that dark place: She had

the stress of caring for an ailing father, the stress of her job, and

years of living with "an abusive husband.”

The one lighter moment in this round of introductions came from

the oldest member of the group. He had been doing pretty well

lately, and his explanation for his relative happiness was one that

Seinfield's George Costanza would have appreciated. "Usually the

summer is a hard time for me because everybody seems so happy.

But with all the rain we have been having, that hasn't been so much

the case this summer," he said.

Over the course of the next hour, the talk jumped from topic to

topic. There was a discussion of the stigma that the mentally ill face

in our society, particularly in the workplace, and talk too of how

family and friends, after a time, lose their empathy. This was clearly

why many in the group had come —they found the shared under¬

standing to be helpful. The issue of medication came up, and on this

topic, opinions and experiences varied widely. The former execu¬

tive, while still regularly suffering from depression, said that his

medication did "wonders" for him and that his greatest fear was

that it would "stop working.” Others told of having tried one

medication after another before finding a drug regimen that pro¬

vided some relief. Steve Lappen said that medications had never

worked for him, while Dennis Hagler, the other DBSA leader in the

meeting (who also agreed to be identified), said that a high dose of

an antidepressant has made all the difference in the world in his life.

The nurse told of having responded very badly to antidepressants

during her recent hospitalization.

"I had an allergic reaction to five different drugs," she said. "I am

now trying one of the new atypicals [antipsychotics]. I'm hoping

that will work."

After the group sessions ended, people gathered in the cafeteria in

ANECDOTAL THOUGHTS

clutches of two and three, sharing small talk. That made for a pleas¬

ant moment; there was a feeling of social warmth in that room, and

you could see that the evening had lifted the spirits of many. It was

all so ordinary that this easily could have been the wrap-up moment

to a PTA meeting or a church social, and as I walked to the car, it

was that ordinariness that struck me most. In the observer's group,

there had been a businessman, an engineer, a historian, an attorney,

a college professor, a social worker, and a nurse (the other two in

the group hadn't spoken of their work histories). Yet, as far as I

could tell, only the college professor was currently employed. And

that was the puzzle: The people in the observer's group were well

educated and they were all taking psychotropic medications, and

yet many were so plagued by persistent depression and bipolar

symptoms that they couldn't work.

Earlier, Steve had told me that about half of the DBSA members

receive either an SSI or SSDI check because they are, in the govern¬

ment's eyes, disabled by their mental illness. This is the patient type

that has been swelling the SSI and SSDI rolls for the past fifteen

years, while the DBSA has grown into the largest mental health pa¬

tient organization in the country during that time. Psychiatry now

has three classes of medications it uses to treat affective disorders —

antidepressants, mood stabilizers, and atypical antipsychotics —but

for whatever reason, an ever greater number of people are showing

up at DBSA meetings around the country, telling of their persistent

and enduring struggles with depression or mania or both.

Four Stories

In medicine, the personal stories of patients diagnosed with a dis¬

ease are known as "case studies," and it is understood that these an¬

ecdotal accounts, while they might provide insight into a disease

and the treatments for it, cannot prove whether a treatment works.

Only scientific studies that look at outcomes in the aggregate can do

that, and even then the picture that emerges is often a cloudy one.

The reason that anecdotal accounts can't provide such proof is that

l 6

ANATOMY OF AN EPIDEMIC

people may have widely varying reactions to medical treatments,

and that is particularly true in psychiatry. You can find people who

will tell of how psychiatric medications have helped them im¬

mensely; you can find people who will tell of how the drugs have

ruined their lives; and you can find people —and this seems to be the

majority in my experience —who don't know what to think. They

can't quite decide whether the drugs have helped them or not. Still,

as we set out to solve this puzzle of a modern-day epidemic of dis¬

abling mental illness in the United States, anecdotal accounts can

help us identify questions that we will want to see answered in our

search of the scientific literature.

Here are four such life stories.

Cathy Levin

I first met Cathy Levin in 2004, not too long after I had published

my first book on psychiatry, Mad in America. I immediately came to

admire her fierce spirit. The last part of that book explored whether

antipsychotic medications might be worsening the long-term course

of schizophrenia (a topic that is explored in Chapter 6 of this book),

and Cathy, in some ways, objected to that thought. Although she

had initially been diagnosed with bipolar disorder (in 1978), her di¬

agnosis had later been changed to ''schizoaffective,” and she had,

by her own reckoning, been "saved” by an atypical antipsychotic,

Risperdal. The history that I had related in Mad in America threat¬

ened, in some way, her own personal experience, and she called me

several times to tell me how helpful that drug had been to her.

Born in 1960 in a Boston suburb, Cathy grew up in what she re¬

members as a "male-dominated” world. Her father, a professor at a

college in the Boston area, was a veteran of World War II, and her

stay-at-home mom saw such men as the "backbone of the social

order." Her two older brothers, she recalls, "bullied her," and on

more than one occasion, starting when she was quite young, several

boys in her neighborhood molested her. "I cried all the time when I

was a child," she says, and often she pretended to be sick so that she

wouldn't have to go to school, preferring instead to spend her days

alone in her room, reading books.

ANECDOTAL THOUGHTS

Although she did fine academically in high school, she was "a

difficult teenager, hostile, angry, withdrawn." During her second

year in college, at Earlham in Richmond, Indiana, her emotional

troubles worsened. She began partying with the young men on the

football team, eager, she says, "to have sex” but, at the same time,

worried about losing her virginity. "I was confused about being in¬

volved with a guy. I went to a lot of parties and I couldn't concen¬

trate anymore on my studies. I started to flunk out of school."

Cathy was smoking a lot of marijuana, too, and soon she began

acting in an eccentric manner. She borrowed other people's clothes

to wear, trekking around campus in "oversized clogs, a pair of over¬

alls thrown over my regular clothes, a bomber jacket, and a funny

hat I got from the Army-Navy store.” One night, on her way home

from a party, she threw away her glasses for no reason. Her

thoughts about sex gradually bloomed into a fantasy about Steve

Martin, the comedian. Unable to sleep through the night, she would

awaken at four a.m. and go for walks, and at times, it seemed that

Steve Martin was there on campus, stalking her. "I thought he was

in love with me and was running through the bushes just out of

sight,” she says. "He was looking for me.”

Mania and paranoia were combining into a volatile mix. The

breaking point came one evening when she threw a glass object

against the wall in her dorm room. "I didn't clean it up, but instead

was walking around in it. I was, you know, taking the glass out of

my feet. I was completely out of my mind.” School officials called

police and she was rushed off to a hospital, and it was then, a few

days before her eighteenth birthday, that Cathy's medicated life

began. She was diagnosed with manic-depressive illness, informed

that she suffered from a chemical imbalance in the brain, and put on

Haldol and lithium.

For the next sixteen years, Cathy cycled in and out of hospitals.

She "hated the meds" —Haldol stiffened her muscles and caused her

to drool, while the lithium made her depressed —and often she

would abruptly stop taking them. "It feels so great to go off med¬

ication,” she says, and even now, when she remembers that feeling,

she seems to get lost in the pure deliciousness of a memory from the

distant past. "When you go off meds it is like taking off a wet wool

18 • ANATOMY OF AN EPIDEMIC

coat, which you have been wearing even though it's a beautiful

spring day, and suddenly feeling so much better, freer, nicer.” The

problem was that off the drugs, she would "start to decompensate

and become disorganized.”

In early 1994, she was hospitalized for the fifteenth time. She was

seen as chronically mentally ill, occasionally heard voices now, had

a new diagnosis (schizoaffective), and was on a cocktail of drugs:

Haldol, Ativan, Tegretol, Halcion, and Cogentin, the last drug an

antidote to Haldol's nasty side effects. But after she was released

that spring, a psychiatrist told her to try Risperdal, a new anti¬

psychotic that had just been approved by the FDA. "Three weeks

later, my mind was much clearer," she says. "The voices were going

away. I got off the other meds and took only this one drug. I got

better. I could start to plan. I wasn't talking to the devil anymore.

Jesus and God weren't battling it out in my head.” Her father put it

this way: "Cathy is back."

Although several studies funded by the NIMH and the British

government have found that patients, on the whole, don't do any

better on Risperdal and the other atypicals than on the older anti-

psychotics, Cathy clearly responded very well to this new agent. She

went back to school and earned a degree in radio, film, and televi¬

sion from the University of Maryland. In 1998, she began dating

the man she lives with today, Jonathan. In 2005, she took a part-

time job as editor of Voices for Change, a newsletter published by

M-Power, a consumer group in Massachusetts, a position she held

for three years. In the spring of 2008, she helped lead an M-Power

campaign to get the Massachusetts legislature to pass a law that

would protect the rights of psychiatric patients in emergency rooms.

Still, she remains on SSDI — "I am a kept woman," she jokes —and

although there are many reasons for that, she believes that Risper¬

dal, the very drug that has helped her so much, nevertheless has

proven to be a barrier to full-time work. Although she is usually en¬

ergetic by the early afternoon, Risperdal makes her so sleepy that

she has trouble getting up in the morning. The other problem is that

she has always had trouble getting along with other people, and

Risperdal exacerbates that problem, she says. "The meds isolate

you. They interfere with your empathy. There is a flatness to you,

ANECDOTAL THOUGHTS

and so you are uncomfortable with people all the time. They make

it hard for you to get along. The drugs may take care of aggression

and anxiety and some paranoia, those sorts of symptoms, but they

don't help with the empathy that helps you get along with people."

Risperdal has also taken a physical toll. Cathy is five feet, two

inches tall, with curly brown hair, and although she is fairly physi¬

cally fit, she is probably sixty pounds heavier than what would be

considered ideal. She has also developed some of the metabolic

problems, such as high cholesterol, that the atypical antipsychotics

regularly cause. "I can go toe-to-toe with an old lady with a recital

of my physical problems," she says. "My feet, my bladder, my

heart, my sinuses, the weight gain —I have it all.” Even more alarm¬

ing, in 2006 her tongue began rolling over in her mouth, a sign that

she may be developing tardive dyskinesia. When this side effect

appears, it means that the basal ganglia, the part of the brain that

controls motor movement, is becoming permanently dysfunctional,

having been damaged by years of drug treatment. But she can't do

well without Risperdal, and in the summer of 2008, this led to a

moment of deep despair. "I will, of course, look pretty creepy in a

few years, with the involuntary mouth movements," she says.

Such has been her life's course on medications. Sixteen terrible

years, followed by fourteen pretty good years on Risperdal. She be¬

lieves that this drug is essential to her mental health today, and in¬

deed, she could be seen as a local poster child for promoting the

wonders of that drug. Still, if you look at the long-term course of

her illness, and you go all the way back to her first hospitalization at

age eighteen, you have to ask: Is hers a story of a life made better by

our drug-based paradigm of care for mental disorders, or a story of

a life made worse? How might her life have unfolded if when she

suffered her first manic episode in the fall of 1978, she had not

been immediately placed on lithium and Haldol, the doctors instead

trying other means —rest, psychological therapies, etc. —to restore

her sanity? Or if, once she had been stabilized on those medications,

she had been encouraged to wean herself from the drugs? Would

she have spent sixteen years cycling through hospitals? Would she

have gone on SSDI and remained on it ever since? What would her

physical health be like now? What would her subjective experience

2 0

ANATOMY OF AN EPIDEMIC

of life through those years have been like? And if she had been able

to fare well without drugs, how much more might she have accom¬

plished in her life?

This is a question that Cathy, given her experience with Risper¬

dal, had not thought much about before our interviews. But once I

raised it, she seemed haunted by this possibility, and she brought it

up again and again when we met. "I would have been more produc¬

tive without the meds," she said the first time. "It would break my

heart" to think about that, she said later. Another time she lamented

that with a life on antipsychotics, "you lose your soul and you never

get it back. I got stuck in the system and the struggle to take meds."

Finally, she told me this: "The thing I remember, looking back, is

that I was not really that sick early on. I was really just confused. I

had all these issues, but nobody talked to me about that. I wish I

could go off meds even now, but there is nobody to help me do it.

I can't even start a dialogue.”

There is, of course, no way of knowing what a life without meds

might have been like for Cathy Levin. However, later in this book

we will see what science has to reveal about the possible course her

illness might have taken if, at that fateful moment in 1978, after her

initial psychotic episode, she had not been medicated and told that

she would have to take drugs for life. Science should be able to tell

us whether psychiatrists have reason to believe that their paradigm

of drug-based care alters long-term outcomes for the better or for

the worse. But Cathy believes that this is a question that psychia¬

trists never contemplate.

"They don't have any sense about how these drugs affect you

over the long term. They just try to stabilize you for the moment,

and look to manage you from week to week, month to month.

That's all they ever think about."

George Badillo

Today, George Badillo lives in Sound Beach on Long Island, his

neatly kept home only a short drive away from the water. Nearly

fifty years old, he is physically fit, with slightly graying hair swept

back off his forehead, and he has a quick, warm smile. His

ANECDOTAL THOUGHTS

2 1

thirteen-year-old son, Brandon, lives with him —"He is on the foot¬

ball team, the wrestling team, the baseball team, and the honor

roll,'' George says, with understandable pride —and his twenty-

year-old daughter, Madelyne, who is a student at the College of

Staten Island, is visiting him on this day. Even at first glance, you

can see both are happy to have this time together.

Like many who have been diagnosed with schizophrenia, George

remembers being "different" as a child. As a young boy growing up

in Brooklyn, he felt isolated from the other kids, partly because his

Puerto Rican parents spoke only Spanish. "I remember all the other

kids talking and being so friendly and outgoing, mingling with each

other, and I couldn't do that. I'd want to talk with them, but I was

always apprehensive," he recalls. He also had an alcoholic father

who often beat him, and because of that, he began to think that

"people were always plotting and wanting to hurt me.”

Still, George did okay in school, and it wasn't until his late teens,

when he was a student at Baruch College, that his life began going

awry. "I got into the disco life," he explains. "I started doing am¬

phetamines, marijuana, and cocaine, and I liked it. The drugs re¬

laxed me. Only then it got out of hand and the cocaine started

making me think all crazy. I got real paranoid. I felt there were con¬

spiracies and all that. People were after me, and the government was

in on it." Eventually he ran off to Chicago, where he lived with his

aunt and withdrew from the world that he felt was chasing him.

Alarmed, his family coaxed him back home and took him to the

psychiatric unit at Long Island Jewish Hospital, where he was diag¬

nosed as a paranoid schizophrenic. "They are all telling me that my

brain is broken, and that I will be sick for the rest of my life,” he says.

The next nine years passed in a chaotic whirl. Like Cathy Levin,

George hated Haldol and the other antipsychotics he was told to

take, and partly because of that drug-induced despair, he tried to

kill himself multiple times. He fought with his family about the

medications, went on and off the drugs, cycled through several hos¬

pitalizations, and, in 1987, became a father after his eighteen-year-

old girlfriend gave birth to Madelyne. He married his girlfriend,

intent on being a good father, but Madelyne was a sickly child and

George and his wife both suffered breakdowns trying to care for

2 2

ANATOMY OF AN EPIDEMIC

her. His grandmother took Madelyne to Puerto Rico, and George

ended up divorced and living in a home for the disabled. There he

met and married a woman also diagnosed with paranoid schizo¬

phrenia, and after a series of adventures and misadventures in San

Francisco, they, too, got divorced. Despondent and paranoid once

again, in early 1991 George landed in Kings Park Psychiatric Cen¬

ter, a run-down state hospital on Long Island.

Now came his descent into total hopelessness. After he tried to

have a pistol smuggled into the hospital so that he could kill him¬

self, he was given a two-year sentence in the locked facility. Then, as

Christmas neared that year, he grew upset when several of his fellow

patients weren't allowed to go home for the holiday, and so he

helped them escape, breaking a window in his room and tying

sheets together so they could clamber to the ground. The hospital

responded by moving him to a ward for people who had been insti¬

tutionalized for decades. "Now I am on a ward with people urinat¬

ing on themselves," he recalls. "Pm a danger to society and drugged

out. You sit down all day and watch television. You can't even go

outside. I thought my life was over."

George spent eight months on that ward for the hopelessly men¬

tally ill, lost in a haze of drugs. However, at last he was moved to a

unit where he could go outside, and suddenly there was blue sky to

be seen and fresh air to breathe. He felt a spark of hope, and then he

took a very risky step: He began tonguing the antipsychotic medica¬

tion and spitting it out when the staff weren't looking. "I could

think again," he says. "The antipsychotic drugs weren't letting me

think. I was like a vegetable, and I couldn't do anything. I had no

emotions. I sat there and watched television. But now I felt more in

control. And it felt great to feel alive again."

Luckily, George didn't experience a return of psychotic symp¬

toms, and with his body no longer slowed by drugs, he began to jog

and lift weights. He fell in love with another patient in the hospital,

Tara McBride, and in 1995, after they were both discharged from

the hospital to a nearby community residence, she gave birth to

Brandon. George, who had never completely lost touch with his

daughter, Madelyne, now had a new goal in life. "I realize I have a

second chance. I want to be a good parent."

ANECDOTAL THOUGHTS

At first, it didn't go well. Like Madelyne, Brandon had been born

with health problems —he had an intestinal abnormality that re¬

quired surgery —and Tara broke down from that stress and was

rehospitalized. Since George was still living in a residence for the

mentally ill, the state did not deem him fit to care for Brandon and

he was given to Tara's sister to raise. However, in 1998 George

began working part-time as a peer specialist for the New York State

Office of Mental Health, counseling hospitalized patients about

their rights, and three years later, he was able to present himself in

court as someone who could be a good father to Brandon. "My sis¬

ter Madeline and I got custody," he says. "That was the best feeling.

I was just jumping for joy. It was like the first time that someone in

the system got custody of their kids."

The following year, one of George's sisters bought him the house

he lives in today. Although he still receives SSDI, he does contract

work for the federal Substance Abuse and Mental Services Health

Administration and does volunteer work with hospitalized youth in

Long Island. His is a life filled with meaning, and as Brandon's suc¬

cess in school will attest, he is proving to be the good father he

dreamed of becoming. Madelyne, meanwhile, is unabashedly proud

of him. "He wanted to have Brandon and me in his life," she says.

"That made him want to turn around his situation. He wanted to be

a father to us. He is proof that someone can recover from mental

illness."

Although George's story is clearly an inspiring one, it doesn't

prove anything one way or another about the overall merits of

antipsychotics. But it does prompt a clinical question: Given that his

recovery began when he stopped taking antipsychotics, is it possible

that some people ill with a serious mental disorder, like schizophre¬

nia or bipolar illness, might recover in the absence of medication? Is

his story an anomaly, or does it provide insight into what could be a

fairly common path to recovery? George, who today occasionally

takes Ambien or a low dose of Seroquel to sleep at night, believes

that, at least in his case, getting off the drugs was what enabled him

to get well. "If I had stayed on those drugs, I wouldn't be where I

am today. I would be stuck in an adult home somewhere, or in the

hospital. But I'm recovered. I still have some strange ideas, but now

ANATOMY OF AN EPIDEMIC

I keep them to myself. And I weather whatever emotional stress

comes up. It stays with me for a few weeks and then it goes away."

Monica Briggs

Monica Briggs is a tall, intense woman and, like so many people ac¬

tive in the "peer recovery” movement, immensely likeable. On the

day that I have lunch with her, at a restaurant in South Boston, she

comes hobbling over to the booth leaning on a cane, as she recently

injured herself, and when I ask how she traveled here, she smiles,

slightly pleased with herself. "On my bike," she says.

Monica, who was born in 1967, is from Wellesley, Massachu¬

setts, and as a teenager growing up in that affluent community, she

seemed like the last person who might have a life of mental illness

awaiting her. She came from an accomplished family —her mother

was a professor at Wellesley, while her father taught at several

Boston-area colleges —and Monica was a child who excelled at

whatever she chose to do. She was a good athlete, earned top

grades, and showed a particular talent for art and writing. Upon

graduating from high school, she received several scholarship

awards, and when she entered Middlebury College in Vermont in

the fall of 1985, she believed that her life would follow a very con¬

ventional path. "I thought I'd go to school, marry, have a chocolate

Labrador, and a home in the suburbs, with the SUV. ... I thought it

would all happen like that."

A month into her freshman year at Middlebury, Monica was

blindsided by a severe depressive episode that seemed to have no

cause. She'd never had emotional problems before, nothing bad had

happened at Middlebury, and yet the depression hit her with such

force that she had to leave school and return home. "I was someone

who had never quit anything before," she says. "I thought my life

was over. I thought this was a failure I could never recover from.”

A few months later, she returned to Middlebury. She was taking

an antidepressant (desipramine), and as spring neared, her spirits

began to lift. However, they didn't just rise to a "normal” level. In¬

stead, they soared beyond to what seemed a much better place. She

now had energy to burn. She took long runs and threw herself into

ANECDOTAL THOUGHTS

her art, dashing off accomplished self-portraits in charcoals and

pastels. She had so little need for sleep that she started a T-shirt

business. "It was fantastic, great,” she says. "I am not thinking that

I am God, or anything, but I am thinking I am pretty close to God

at that point. This goes on for several weeks, and then I crash for

what seems like forever.”

This was the start of Monica's long battle with bipolar disorder.

Depression had given way to mania followed by worse depression.

Although she managed to complete her freshman year, with an

A-minus average, she began cycling through depressive and manic

episodes, and in May of her sophomore year, she gulped down

handfuls of sleeping spills, intending to kill herself. Over the next

fifteen years, she was hospitalized thirty times. While lithium kept

her mania in check, the suicidal depression always came back, her

doctors prescribing one antidepressant after another in an attempt

to find the magic pill that would help her stay well.

There were times, between the hospitalizations, when she was

fairly stable, and she made the most of them. In 1994, she earned a

bachelor's degree from Massachusetts College of Art and Design,

and after that she worked for various advertising agencies and pub¬

lishing houses. She became active in the Depressive and Manic-

Depressive Association and developed its logo, the "bipolar bear."

But in 2001, after she was fired from her job for having stayed

home for a week due to her depression, her suicidal impulses re¬

turned with a vengeance. She bought a gun, only to have it misfire

six times when she tried to shoot herself. She spent three nights on a

bridge that crossed a highway, desperately wanting to fling herself

onto the roadway below, but refraining from doing so because she

thought she might cause a crash that would hurt others. She was

hospitalized several times, and then, in 2002, her mother died from

pancreatic cancer, and her mental struggles took an even worse

turn. "I am psychotic, hallucinating, seeing things. I think I have

super powers and can change the way time flows. I think I have ten-

feet wings and that I can fly.”

That was the year she went on SSDI. Seventeen years after her

initial manic episode, she had officially become disabled by bipolar

disorder. "I hate it,” she says. "I am a Wellesley girl on welfare, and

ANATOMY OF AN EPIDEMIC

that’s not what Wellesley girls are supposed to do. It is so corrosive

to your self-esteem.”

As might be guessed, given that she arrived at the diner on a

bicycle, having pedaled there during her lunch break at work, Mon¬

ica's life eventually took a turn for the better. In 2006, she stopped

taking an antidepressant, and that triggered a "dramatic change.”

Her depression lifted, and she began working part-time at the

Transformation Center, a Boston peer-run organization that helps

people with psychiatric diagnoses. Although the lithium she has

continued to take has its drawbacks —"my ability to create artwork

is gone,” she says —it hasn't exacted too great a physical toll. While

she has a thyroid problem and suffers from tremors, her kidneys are

fine. "I'm in recovery now," she says, and as we get up to leave the

diner, she makes it clear that she would like to secure a full-time job

and get off SSDI. "Being on welfare is a phase in my life," she says

emphatically, "not an end.”

Such has been the long arc of her illness. As a clinical study, her

story appears to tell simply of the benefits of lithium. That drug ap¬

parently kept her mania in check for decades, and as a monotherapy,

it has helped keep her stable since 2006. Still, after years of drug

treatment, she ended up on SSDI, and as such, her story illustrates

one of the core mysteries of this disability epidemic. How did some¬

one so smart and accomplished end up on that governmental pro¬

gram? And if we wind the clock back to the spring of 1986, a

perplexing question appears: Did she suffer her first manic episode

because she was "bipolar," or did the antidepressant induce the

mania? Is it possible that the drug converted her from someone who

had suffered a depressive episode into a bipolar patient, and thus

put her onto a path of chronic illness? And did the subsequent use

of antidepressants alter the course of her "bipolar illness," for one

reason or another, for the worse?

To put it another way, in the world of people who attend DBSA

meetings, how often do they tell of becoming bipolar after initial

treatment with an antidepressant?

ANECDOTAL THOUGHTS

Dorea Vierling-Clausen

If you had met Dorea Vierling-Clausen in 2002, when she was

twenty-five years old, she would have told you that she was "bi¬

polar." She'd been so diagnosed in 1998, her psychiatrist explaining

that she suffered from a chemical imbalance in the brain, and by

2002 she was on a cocktail of drugs that included an antipsychotic,

Zyprexa. But by the fall of 2008, she was off all psychiatric medica¬

tions (and had been for two years), she was thriving in a life that re¬

volved around marriage, motherhood, and postdoctoral research at

Massachusetts General Hospital, and she was convinced that her

"bipolar" years had all been a big mistake. She believes that she was

one of the millions of Americans caught up in a frenzy to diagnose

the disorder, and it very nearly ended with her becoming a mental

patient for life.

"I escaped by the skin of my teeth,” she says.

Dorea tells me her story while sitting in the kitchen of her condo¬

minium in Cambridge, Massachusetts. Her spouse, Angela, is here,

and their two-year-old daughter is sleeping in the next room. With

her freckles and slightly frizzy hair, and evident zest for life, Dorea

seems like someone who might have been a bit of a mischievous

child, and to a certain extent, that is how she remembers herself. "I

was extremely smart, at the far end of that spectrum, and so I was

the geeky kid. But I had friends. I was skillful at social navigation —

I was also the funny kid.” If there was one thing amiss in her life as

a child, it was that she was overly emotional, prone to "angry out¬

bursts” and "crying” jags. "Delightful, but odd” is how she sums

up her seven-year-old self.

Like many bright "odd” kids, Dorea found pursuits she excelled

at. She developed a passion for the trumpet and became an accom¬

plished musician. A top student, she had a particular talent for

mathematics. In high school, she ran on the track team and had

many friends. However, she remained quite emotional —that part of

her personality did not go away —and there was a very real source

of distress in her life: She was coming to understand that she was a

lesbian. Her parents were "extremely conservative Christians," and

while she loved them and deeply admired their devotion to social

2 8

ANATOMY OF AN EPIDEMIC

justice —her father, a physician, volunteered half of his time to work

in a clinic he'd founded in Denver's tough "Five Points" neighbor¬

hood—she feared that because of their religious beliefs, they

wouldn't accept her homosexuality. After Dorea's freshman year at

Peabody Institute, a prestigious music conservatory in Baltimore,

she took a deep breath and told them her secret. "It went pretty

much as awfully as could be expected," she says. "There were tears,

a gnashing of teeth. It was so desperately ingrained in their religious

thinking.”

Dorea barely spoke to her parents for the next two years. She

dropped out of Peabody and fell in with a punk crowd that lived in

downtown Denver. The once aspiring trumpeter now ran around

town with a shaved head and wearing combat boots. After working

for a year at a shop that restored rugs, she enrolled at Metro State

College, a commuter school. There she struggled constantly with

her emotions, often crying in public, and soon she began seeing a

therapist, who diagnosed her as depressed. Eventually she began to

take an antidepressant, and during finals week in the spring of

1998, she found that she couldn't sleep. When she showed up at her

therapist's office agitated and a little manic, he had a new explan¬

ation for all that bedeviled her: bipolar illness. "I was told it was

chronic and that my episodes would increase in frequency, and that

I would need to be on drugs for the rest of my life," she recalls.

Although this foretold a bleak future, Dorea took comfort in the

diagnosis. It explained why she was so emotional. This also was a

diagnosis common to many great artists. She read Kay Jamison's

book Touched with Fire and thought, "I am just like all these fa¬

mous writers. This is great." She now had a new identity, and as she

resumed her academic career, she arrived at each new institution —

first at the University of Nebraska for an undergraduate degree and

then at Boston University for a Ph.D. in math and biology —with a

"giant box of pills." The cocktail she took usually included a mood

stabilizer, an antidepressant, and a benzodiazepine for anxiety, al¬

though the exact combination was always changing. One drug

would make her sleepy, another would give her tremors, and none

of the cocktails seemed to bring her emotional tranquility. Then, in

ANECDOTAL THOUGHTS

2001, she was put on an antipsychotic, Zyprexa, which, in a sense,

worked like a charm.

"You know what?" she says today, amazed by what she is about

to confess. "I loved the stuff. I felt like I finally found the answer.

Because what do you know. I have no emotions. It was great. I

wasn't crying anymore."

Although Dorea did well academically at Boston University, she

still felt "really stupid” on Zyprexa. She slept ten, twelve hours a

day, and like so many people on the drug, she began to blimp up,

putting on thirty pounds. Angela, who had met and fallen in love

with Dorea prior to her going on Zyprexa, felt a sense of loss: "She

wasn't as lively anymore, she didn't laugh," she says. But they both

understood that Dorea needed to be on the medications, and they

began organizing their lives —and their plans for the future —

around her bipolar illness. They attended DBSA meetings, and they

began to think that Dorea should scale back her career goals. She

probably wouldn't be able to handle the stress of postdoctoral re¬

search; her previous work in a rug shop seemed about right. "That

sounds insane now," says Angela, who is a professor of mathe¬

matics at Lesley College. "But at the time, she wasn't a very resilient

person, and she was becoming more and more dependent. I had to

bear the weight of caretaking.''

Dorea's possibilities were diminishing, and she might have con¬

tinued down that path except for the fact that in 2003 she stumbled

across some literature that raised questions about Zyprexa's long¬

term safety and the merits of antipsychotic drugs. That led her to

wean herself from that drug, and while that process was "pure

hell" —she suffered terrible anxiety, severe panic attacks, paranoia,

and horrible tremors —she eventually did get off that medication.

She then decided to see if she could get off the benzodiazepine she

was taking, Klonopin, and that turned into another horrible with¬

drawal experience, as she suffered such severe headaches she'd be in

bed by noon. Still, she was gradually undoing her drug cocktail, and

that caused her to question her bipolar diagnosis. She had first seen

a therapist because she cried too much. There had been no mania —

her sleeplessness and agitation hadn't arisen until after she had been

ANATOMY OF AN EPIDEMIC

placed on an antidepressant. Could she just have been a moody

teenager who had some growing up to do?

"I had always thought before that I was one of those cases where

the illness was clearly biological," she says. "It couldn't have been

situational. Nothing had gone terribly wrong in my life. But then I

thought, well, I came out as a lesbian, and I had no family support.

Duh. That could have been kind of stressful."

The mood stabilizers were the last to go, and on November 22,

2006, Dorea pronounced herself drug free. "It was fabulous. I was

surprised to find out who I was after all these years,” she says,

adding that having shed the bipolar label in her own mind, her sense

of personality responsibility changed, too. "When I was 'bipolar,' I

had an excuse for any unpredictable or unstable behavior. I had per¬

mission to behave in that way, but now I am holding myself to the

same behavioral standards as everyone else, and it turns out I can

meet them. This is not to say that I don't have bad days. I do, and

I may still worry more than the average Joe, but not that much

more.”

Dorea's research at Massachusetts General Hospital focuses on

how vascular activity affects brain function, and given that her

struggles with "mental illness” can seemingly be chalked up as a

case of misdiagnosis —"I have this fantasy of being undiagnosed as

bipolar,” she says —it may seem that her story is irrelevant to this

book. But, in fact, her story raises a possibility that could go a long

way toward explaining the epidemic of disabling mental illness in

the United States. If you expand the boundaries of mental illness,

which is clearly what has happened in this country during the past

twenty-five years, and you treat the people so diagnosed with psy¬

chiatric medications, do you run the risk of turning an angst-ridden

teenager into a lifelong mental patient? Dorea, who is an extremely

smart and capable person, barely escaped going down that path.

Hers is a story of a possible iatrogenic process at work, of an other¬

wise normal person being made chronically sick by diagnosis and

subsequent treatment. And thus we have to wonder: Do we have a

paradigm of care that can, at times, create mental illness?

ANECDOTAL THOUGHTS

• 3 1

The Parents' Dilemma

Early during the course of my reporting for this book, I met with two

families in the Syracuse area who, a few years back, had been faced

with deciding whether to put their children on a psychiatric medica¬

tion. The reason that I had paired these two families up in my mind

was that they had come to opposite conclusions about what was best

for their child, and I was curious to know what information they had

at their disposal when they made their decisions.

I first went to see Gwendolyn and Sean Oates. They live on the

south side of Syracuse, in a pleasant house perched on a slight hill.

A gracious, biracial couple, they have two children, Nathan and

Alia, and as we spoke, Nathan —who was then eight years old —

spent most of the time sprawled out in the living room, drawing

pictures in a sketchbook with colored pencils.

"We began to worry about him when he was three,” his mother

says. "We noticed that he was hyperactive. He couldn't sit through

a meal, he couldn't even sit down. Dinnertime consisted of him run¬

ning around the table. It was the same thing in his preschool —he

couldn't sit still. He wasn't sleeping either. It would take us until

nine thirty or ten p.m. to get him down. He would be kicking and

screaming. These were not normal temper tantrums."

They first took Nathan to his pediatrician. However, she was re¬

luctant to diagnose him, and so they took him to a psychiatrist, who

quickly concluded that Nathan suffered from "attention deficit hy¬

peractivity disorder.” His problem, the psychiatrist explained, was

"chemical" in kind. Although they were nervous about putting

Nathan on Ritalin —"We were going through this on our own,

and we didn't know anything about ADHD," his mother says —

kindergarten was looming, and they reasoned that it would be the

best thing for him. "The hyperactivity was holding him back from

learning,” his mother says. "The school didn't even want us to send

him to kindergarten, but we said, 'No, we are going to.' We made

the decision to keep him moving forward.”

At first, there was a period of "trial and error" with the medica¬

tions. Nathan was put on a high dose of Ritalin, but "he was like a

ANATOMY OF AN EPIDEMIC

3 2

zombie,” his mother recalls. "He was calm but he didn't move. He

stared off into space.” Nathan was then switched to Concerta, a

long-lasting stimulant, and he stabilized well on it. However, at

some point, Nathan began to exhibit obsessive behaviors, such as

refusing to step on the grass or constantly needing to have some¬

thing in his hands, and he was put on Prozac to control those symp¬

toms. While on that two-drug combo, he started having terrible

"rages.” He kicked out his bedroom window during one episode,

and he repeatedly threatened to kill his sister and even his mother.

He was taken off the Prozac, and although his behavior improved

somewhat, he continued to be quite aggressive, and he was diag¬

nosed as suffering from both bipolar and ADHD.

"They say that ADHD and bipolar go hand in hand," his mother

says. "And now that we know that he is bipolar, too, we think he

will probably be on drugs for the rest of his life.”

Since that time, Nathan has been on a drug cocktail. When I

visited, he was taking Concerta in the morning, Ritalin in the after¬

noon, and three low doses of Risperdal —an antipsychotic —at

various times during the day. This combo, his parents say, works

fairly well for him. While Nathan is still moody, he doesn't fly off

into total rages, and his hostility toward his younger sister has

abated. He does struggle with his schoolwork, but he is moving

ahead from grade to grade, and he gets along fairly well with his

classmates. The biggest worry that his parents have about the med¬

ications is that they may be stunting his growth. Nathan is smaller

than his sister, even though he is three years older. However, the

physician's assistant and others who are treating Nathan don't talk

much about how the drugs may affect him over the long term. "They

don't worry about that," his father says. "It's helping him now.”

At the end of the interview, Nathan shows me his drawings. He is

into sharks and dinosaurs, and after I tell him how much I like his

artwork, he seems almost to blush. He has been quiet most of the

time I have been there, and even a little subdued, but we shake

hands as I get ready to leave, and he seems, at that particular

moment, to be a very sweet and gentle kid.

ANECDOTAL THOUGHTS

Jason and Kelley Smith live on the west side of Syracuse, about

thirty minutes distant from the Oates family, and when I knocked

on their door, it was their seven-year-old daughter, Jessica, who an¬

swered. It appeared that she had been waiting for me, and once I

had my tape recorder on, she plunked down on the couch between

her mother and me, ready to pipe in with her side of the story. "Jes¬

sica,” her father says a short while later, "has a lot of charisma.”

Jessica's behavioral problems began at age two when she was

sent to day care. When she got angry, she would hit and bite the

other children. At home, she started having "night terrors" and all-

out meltdowns. "The mildest thing would trigger her and she would

be off," her mother says.

The Smiths turned to their local school district for help. The dis¬

trict recommended that Jessica go to a "special ed” preschool in

north Syracuse, and when she continued to behave aggressively at

that school, they were told to take Jessica to the Health Sciences

Center at the State University of New York for a psychiatric evalua¬

tion. There they saw a nurse practitioner, who immediately con¬

cluded that Jessica was "bipolar.” The practitioner explained that

Jessica had a chemical imbalance and recommended that Jessica be

put on a cocktail of three drugs: Depakote, Risperdal, and lithium.

"It blew my mind, especially the thought of putting her on anti-

psychotics," Jason says. "She was four years old.”

He and his wife left that consultation not knowing what to do.

Kelley works for Oswego County's family service agency, and she

knew of many troubled children who had been put on psychiatric

medications. In that setting, the county expected parents to comply

with medical advice. "There was part of me that thought maybe Jes¬

sica is bipolar, that's what it is," Kelley says. Moreover, SUNY

Health Sciences told the Smiths that the center wouldn't see Jessica

again if she weren't medicated. All of this pointed to following the

center's advice —the "experts are telling you that you need to do

this, and that it is biological," Jason says —but he had previously

worked as a pharmacy technician and knew that drugs could have

powerful side effects. "I was scared out of my mind."

Kelley used the Internet to research the drugs that had been rec¬

ommended. However, she couldn't find any study that told of good

ANATOMY OF AN EPIDEMIC

long-term outcomes for children placed on such drug cocktails, and

even the short-term side effects, she remembers, "were scary."

Meanwhile, Jessica's pediatrician told them she thought it would be

"absurd” to put Jessica on psychiatric drugs; Jason and Kelley's

families also thought it would be a mistake. Jason remembered how

a few years earlier talk therapy had helped him address his own

"anger management" issues, and if he had been able to change

without the use of medications, couldn't Jessica change her behav¬

ior too?

"We just didn't want to accept [the bipolar diagnosis], Jessica is

such an outgoing child, and we like to think she is gifted,” Kelley

says. "And she had made so much progress from the time she was

two years old. We just couldn't see giving her the medications."

They made that decision in 2005, and three years later, they say,

Jessica is doing well. She gets mostly A's in school; her teachers now

think that her earlier bipolar diagnosis was "crazy." While she does

sometimes quarrel with other kids and will lash back verbally if an¬

other child teases her, she knows that she can't hit anyone. At home,

she still has the occasional meltdown, but her emotional outbursts

are not so extreme as before. Jessica even has her own advice on

how all parents should handle such tirades: "They should say [to

their child] 'come here,' and then they should rub them on the back

so they feel better and so they can't have a meltdown, and so when

they stop having a meltdown, that's what they will remember."

Before I leave, Jessica reads to me the book The Little Old Lady

Who Was Not Afraid of Anything, and more than once she jumps

to the floor to act out a scene. "Even with her behavioral issues,

everybody loves her," her father says. "And that's what we were

afraid of, with the medication, was that it would totally change her,

and her personality. We didn't want to impair her faculties. We just

want her to grow up to be healthy and to succeed in life.”

Two different families, two different decisions. Both families now

saw their decision as the right one, and both believed that their child

was on a better path than he or she otherwise would have been.

That was heartening, and I promised to check in with both families

ANECDOTAL THOUGHTS

later, toward the end of my reporting for this book. Still, Nathan

and Jessica were clearly on different paths, and as I drove back to

Boston, all I could think about was how both sets of parents had

needed to make their decision, on whether to medicate their child,

in a scientific vacuum. Did their child really suffer from a chemical

imbalance? Were there studies showing that drug treatment for

ADHD or juvenile bipolar illness is beneficial over the long term? If

you put a young child on a drug cocktail that includes an anti¬

psychotic, how will it affect his or her physical health? Can the child

expect to become a healthy teenager, a healthy adult?

Part Two

The Science of

Psychiatric Drugs

The Roots of an Epidemic

"Americans have come to believe that science is

capable of almost everything."

-DR. LOUIS M. ORR, AMA PRESIDENT (l958)'

It may seem odd to begin an investigation of a modern-day epi¬

demic with a visit back to one of the great moments in medical his¬

tory, but if we are going to understand how our society came to

believe that Thorazine kicked off a psychopharmacological revolu¬

tion, we need to go back to the laboratory of German scientist Paul

Ehrlich. He was the originator of the notion that "magic bullets"

could be found to fight infectious diseases, and when he succeeded,

society thought that the future would bring miracle cures of every

kind.

Born in East Prussia in 1854, Ehrlich spent his early years as a

scientist researching the use of aniline dyes as biological stains. He

and others discovered that the dyes, which were used in the textile

industry to color cloth, had a selective affinity for staining the cells

of different organs and tissues. Methyl blue would stain one type of

cell, while methyl red stained a different type. In an effort to explain

this specificity, Ehrlich hypothesized that cells had molecules that

protruded into the surrounding environment, and that a chemical

dye fit into these structures, which he called receptors, in the same

way that a key fits into a lock. Every type of cell had a different

lock, and that was why methyl blue stained one type of cell and

methyl red another —they were keys specific to those different locks.

ANATOMY OF AN EPIDEMIC

Ehrlich began doing this research in the 1870s, while he was a

doctoral student at the University of Leipzig, and this was the same

period that Robert Koch and Louis Pasteur were proving that mi¬

crobes caused infectious diseases. Their findings led to a thrilling

thought: If the invading organism could be killed, the disease could

be cured. The problem, most scientists at the time concluded, was

that any drug that was toxic to the microbe would surely poison the

host. "Inner disinfection is impossible," declared scientists at an

1882 Congress of Internal Medicine in Germany. But Ehrlich's stud¬

ies with aniline dyes led him to a different conclusion. A dye could

stain a single tissue in the body and leave all others uncolored. What

if he could find a toxic chemical that would interact with the invad¬

ing microbe but not with the patient's tissues? If so, it would kill the

germ without causing any harm to the patient.

Ehrlich wrote:

If we picture an organism as infected by a certain species of

bacterium, it will be easy to effect a cure if substances have

been discovered which have a specific affinity for these bacte¬

ria and act on these alone. (If) they possess no affinity for the

normal constituents of the body, such substances would then

be magic bullets. 2

In 1899, Ehrlich was appointed director of the Royal Institute of

Experimental Therapy in Frankfurt, and there he began his search

for a magic bullet. He focused on finding a drug that would selec¬

tively kill trypanosomes, which were one-celled parasites that

caused sleeping sickness and a number of other illnesses, and he

soon settled on an arsenic compound, atoxyl, as the best magic-

bullet candidate. This would be the chemical he would have to

manipulate so it fit into the parasite's "lock" while not opening the

lock on any human cells. He systematically created hundreds of

atoxyl derivatives, testing them again and again against try¬

panosomes, but time and time again he met with failure. Finally, in

1909, after Ehrlich had tested more than nine hundred compounds,

one of his assistants decided to see if compound number 606 would

THE ROOTS OF AN EPIDEMIC

kill another recently discovered microbe, Spirochete! pallida, which

caused syphilis. Within days, Ehrlich had his triumph. The drug,

which came to be known as salvarsan, eradicated the syphilis

microbe from infected rabbits without harming the rabbits at all.

"This was the magic bullet!" wrote Paul de Kruif in a 1926 best¬

seller. "And what a safe bullet!” The drug, he added, produced

"healing that could only be called biblical." 3

Ehrlich's success inspired other scientists to search for magic bul¬

lets against other disease-causing microbes, and although it took

twenty-five years, in 1935 Bayer chemical company provided medi¬

cine with its second miracle drug. Bayer discovered that sulfanil¬

amide, which was a derivative of an old coal-tar compound, was

fairly effective in eradicating staphylococcal and streptococcal in¬

fections. The magic bullet revolution was now truly under way, and

next came penicillin. Although Alexander Fleming had discovered

this bacteria-killing mold in 1928, he and others had found it diffi¬

cult to culture, and even when they'd succeeded in growing it, they

hadn't been able to extract and purify sufficient quantities of the ac¬

tive ingredient (penicillin) to turn it into a useful drug. But in 1941,

with World War II raging, both England and the United States saw

a desperate need to surmount this hurdle, for wound infections had

always been the big killer during war. The United States asked

scientists from Merck, Squibb, and Pfizer to jointly work on this

project, and by D-Day in 1944, British and American sources were

able to produce enough penicillin for all of the wounded in the

Normandy invasion.

"The age of healing miracles had come at last,” wrote Louis

Sutherland, in his book Magic Bullets, and indeed, with the war

over, medicine continued its great leap forward. 4 Pharmaceutical

companies discovered other broad-acting antibiotics —streptomycin,

Chloromycetin, and Aureomycin, to name a few —and suddenly

physicians had pills that could cure pneumonia, scarlet fever, diph¬

theria, tuberculosis, and a long list of other infectious diseases.

These illnesses had been the scourge of mankind for centuries, and

political leaders and physicians alike spoke of the great day at hand.

In 1948, U.S. secretary of state George Marshall confidently pre-

ANATOMY OF AN EPIDEMIC

dieted that infectious diseases might soon be wiped from the face of

the earth. A few years later, President Dwight D. Eisenhower called

for the "unconditional surrender" of all microbes. 5

As the 1950s began, medicine could look back and count numer¬

ous other successes as well. Pharmaceutical firms had developed im¬

proved anesthetics, sedatives, antihistamines, and anticonvulsants,

evidence of how scientists were getting better at synthesizing chem¬

icals that acted on the central nervous system in helpful ways. In

1922, Eli Lilly had figured out how to extract the hormone insulin

from the pancreas glands of slaughterhouse animals, and this pro¬

vided doctors with an effective treatment for diabetes. Although re¬

placement insulin didn't rise to the level of a magic-bullet cure for

the illness, it came close, for it provided a biological fix for what

was missing in the body. In 1950, British scientist Sir Henry Dale,

in a letter to the British Medical Journal, summed up this extra¬

ordinary moment in medicine's long history: "We who have been able

to watch the beginning of this great movement may be glad and

proud to have lived through such a time, and confident that an even

wider and more majestic advance will be seen by those living

through the fifty years now opening." 6

The United States geared up for this wondrous future. Prior to

the war, most basic research had been privately funded, with An¬

drew Carnegie and John D. Rockefeller the most prominent bene¬

factors, but once the war ended, the U.S. government established

the National Science Foundation to federally fund this endeavor.

There were still many diseases to conquer, and as the nation's lead¬

ers looked around for a medical field that had lagged behind, they

quickly found one that seemed to stand above all the rest. Psychia¬

try, it seemed, was a discipline that could use a little help.

Imagining a New Psychiatry

As a medical specialty, psychiatry had its roots in the nineteenth-

century asylum, its founding moment occurring in 1844, when

thirteen physicians who ran small asylums met in Philadelphia to

THE ROOTS OF AN EPIDEMIC

form the Association of Medical Superintendents of American Insti¬

tutions for the Insane. At that time, the asylums provided a form of

environmental care known as moral therapy, which had been intro¬

duced into the United States by Quakers, and for a period, it pro¬

duced good results. At most asylums, more than 50 percent of

newly admitted patients would be discharged within a year, and

a significant percentage of those who left never came back. A

nineteenth-century long-term study of outcomes at Worcester State

Lunatic Asylum in Massachusetts found that 58 percent of the 984

patients discharged from the asylum remained well throughout the

rest of their lives. However, the asylums mushroomed in size in the

latter part of the 1800s, as communities dumped the senile elderly

and patients with syphilis and other neurological disorders into the

institutions, and since these patients had no chance of recovering,

moral therapy came to be seen as a failed form of care.

At their 1892 meeting, the asylum superintendents vowed to

leave moral therapy behind and instead utilize physical treatments.

This was the dawn of a new era in psychiatry, and in very short

order, they began announcing the benefits of numerous treatments

of this kind. Various water therapies, including high-pressure show¬

ers and prolonged baths, were said to be helpful. An injection of ex¬

tract of sheep thyroid was reported to produce a 50 percent cure

rate at one asylum; other physicians announced that injections of

metallic salts, horse serum, and even arsenic could restore lucidity

to a mad mind. Henry Cotton, superintendent at Trenton State

Hospital in New Jersey, reported in 1916 that he cured insanity by

removing his patients' teeth. Fever therapies were said to be benefi¬

cial, as were deep-sleep treatments, but while the initial reports of

all these somatic therapies told of great success, none of them stood

the test of time.

In the late 1930s and early 1940s, asylum psychiatrists embraced

a trio of therapies that acted directly on the brain, which the popu¬

lar media —at least initially— reported as "miracle” cures. First

came insulin coma therapy. Patients were injected with a high dose

of insulin, which caused them to lapse into hypoglycemic comas,

and when they were brought back to life with an injection of glu¬

cose, the New York Times explained, the "short circuits of the brain

ANATOMY OF AN EPIDEMIC

vanish, and the normal circuits are once more restored and bring

back with them sanity and reality." 7 Next came the convulsive ther¬

apies. Either a poison known as Metrazol or electroshock was used

to induce a seizure in the patient, and when the patient awoke, he or

she would be free of psychotic thoughts and happier in spirit —or so

the asylum psychiatrists said. The final "breakthrough" treatment

was frontal lobotomy, the surgical destruction of the frontal lobes

apparently producing an instant cure. This "surgery of the soul,”

the New York Times explained, "transforms wild animals into

gentle creatures in the course of a few hours." 8

With such articles regularly appearing in major newspapers and

magazines like Harper's, Reader's Digest, and the Saturday Evening

Post, the public had reason to believe that psychiatry was making

great strides in treating mental illness, participating in medicine's

great leap forward, but then, in the wake of World War II, the pub¬

lic was forced to confront a very different reality, one that produced

a great sense of horror and disbelief. There were 425,000 people

locked up in the country's mental hospitals at that time, and first

Life magazine and then journalist Albert Deutsch, in his book The

Shame of the States, took Americans on a photographic tour of the

decrepit facilities. Naked men huddled in barren rooms, wallowing

in their own feces. Barefoot women clad in coarse tunics sat

strapped to wooden benches. Patients slept on threadbare cots in

sleeping wards so crowded that they had to climb over the foot

of their beds to get out. These images told of unimaginable neglect

and great suffering, and at last, Deutsch drew the inevitable com¬

parison:

As I passed through some of Byberry's wards, I was reminded

of the Nazi concentration camps at Belsen and Buchenwald. I

entered buildings swarming with naked humans herded like

cattle and treated with less concern, pervaded by a fetid odor

so heavy, so nauseating, that the stench seemed to have al¬

most a physical existence of its own. I saw hundreds of pa¬

tients living under leaking roofs, surrounded by moldy,

decaying walls, and sprawling on rotting floors for want of

seats or benches.’

THE ROOTS OF AN EPIDEMIC

The nation clearly needed to remake its care of the hospitalized

mentally ill, and even as it contemplated that need, it found reason

to worry about the mental health of the general population. During

the war, psychiatrists had been charged with screening draftees for

psychiatric problems, and they had deemed 1.75 million American

men mentally unfit for service. While many of the rejected draftees

may have been feigning illness in order to avoid conscription, the

numbers still told of a societal problem. Many veterans returning

from Europe were also struggling emotionally, and in September

1945, General Lewis Hershey, who was the director of the Selective

Service System, told Congress that the nation badly needed to ad¬

dress this problem, which had remained hidden for so long. "Men¬

tal illness was the greatest cause of noneffectiveness and loss of

manpower that we met” during the war, he said. 10

With mental illness now a primary concern for the nation —and

this awareness coming at the very time that antibiotics were taming

bacterial killers—it was easy for everyone to see where a long-term

solution might be found. The country could put its faith in the

transformative powers of science. The existing "medical" treatments

said to be so helpful—insulin coma, electroshock, and lobotomy —

would have to be provided to more patients, and then long-term so¬

lutions could arise from the same process that had produced such

astonishing progress in fighting infectious diseases. Research into

the biological causes of mental illnesses would lead to better treat¬

ments, both for those who were seriously ill and those who were

only moderately distressed. "I can envisage a time arriving when we

in the field of Psychiatry will entirely forsake our ancestry, forget¬

ting that we had our beginnings in the poorhouse, the workhouse

and the jail," said Charles Burlingame, director of the Institute of

the Living in Hartford, Connecticut. "I can envisage a time when

we will be doctors, think as doctors, and run our psychiatric institu¬

tions in much the same way and with much the same relationships

as obtain in the best medical and surgical institutions." 11

In 1946, Congress passed a National Mental Health Act that put

the federal government's economic might behind such reform. The

government would sponsor research into the prevention, diagnosis,

and treatment of mental disorders, and it would provide grants to

ANATOMY OF AN EPIDEMIC

states and cities to help them establish clinics and treatment centers.

Three years later, Congress created the National Institute of Mental

Health (NIMH) to oversee this reform.

"We must realize that mental problems are just as real as physical

disease, and that anxiety and depression require active therapy as

much as appendicitis or pneumonia," wrote Dr. Howard Rusk, a

professor at New York University who penned a weekly column for

the New York Times. "They are all medical problems requiring

medical care." 12

The stage had now been set for a transformation of psychiatry and

its therapeutics. The public believed in the wonders of science, the

nation saw a pressing need to improve its care of the mentally ill, and

the NIMH had been created to make this happen. There was the

expectation of great things to come and, thanks to the sales of anti¬

biotics, a rapidly growing pharmaceutical industry ready to capital¬

ize on that expectation. And with all those forces lined up, perhaps

it is no surprise that wonder drugs for both severe and not-so-severe

mental illnesses —for schizophrenia, depression, and anxiety —soon

arrived.

Psychiatry’s Magic Bullets

"It was the first drug cure in all of

psychiatric history."

- NATHAN KLINE

DIRECTOR OF RESEARCH AT ROCKLAND

HOSPITAL IN NEW YORK (l974)‘

STATE

The "magic bullet” model of medicine that had led to the discovery

of the sulfa drugs and antibiotics was very simple in kind. First,

identify the cause or nature of the disorder. Second, develop a

treatment to counteract it. Antibiotics killed known bacterial in¬

vaders. Eli Lilly's insulin therapy was a variation on the same

theme. The company developed this treatment after researchers

came to understand that diabetes was due to an insulin deficiency.

In each instance, knowledge of the disease came first —that was the

magic formula for progress. However, if we look at how the first

generation of psychiatric drugs was discovered, and look too at

how they came to be called antipsychotics, anti-anxiety agents, and

antidepressants— words that indicate they were antidotes to specific

disorders —we see a very different process at work. The psychophar¬

macology revolution was born from one part science and two parts

wishful thinking.

ANATOMY OF AN EPIDEMIC

Neuroleptics, Minor Tranquilizers,

and Psychic Energizers

The story of the discovery of Thorazine, the drug that is remem¬

bered today as having kicked off the psychopharmacology "revolu¬

tion," begins in the 1940s, when researchers at Rhone-Poulenc, a

French pharmaceutical company, tested a class of compounds

known as phenothiazines for their magic-bullet properties. Phe-

nothiazines had first been synthesized in 1883 for use as chemical

dyes, and Rhone-Poulenc's scientists were trying to synthesize phe¬

nothiazines that were toxic to the microbes that caused malaria,

African sleeping sickness, and worm-borne illnesses. Although that

research didn't pan out, they did discover in 1946 that one of their

phenothiazines, promethazine, had antihistaminic properties, which

suggested it might have use in surgery. The body releases histamine

in response to wounds, allergies, and a range of other conditions,

and if this histaminic response is too strong, it can lead to a precipi¬

tous drop in blood pressure, which at the time occasionally proved

fatal to surgical patients. In 1949, a thirty-five-year-old surgeon in

the French Navy, Henri Laborit, gave promethazine to several of his

patients at the Maritime Hospital at Bizerte in Tunisia, and he dis¬

covered that in addition to its antihistaminic properties, it induced a

"euphoric quietude. . . . Patients are calm and somnolent, with a re¬

laxed and detached expression." 2

Promethazine, it seemed, might have use as an anesthetic. At that

time, barbiturates and morphine were regularly employed in medi¬

cine as general sedatives and painkillers, but those drugs suppressed

overall brain function, which made them quite dangerous. But

promethazine apparently acted only on selective regions of the

brain. The drug "made it possible to disconnect certain brain func¬

tions," Laborit explained. "The surgical patient felt no pain, no

anxiety, and often did not remember his operation." 3 If the drug

was used as part of a surgical cocktail, Laborit reasoned, it would

be possible to use much lower doses of the more dangerous anes¬

thetic agents. A cocktail that included promethazine —or an even

PSYCHIATRY'S MAGIC BULLETS • 49

more potent derivative of it, if such a compound could be synthe¬

sized—would make surgery much safer.

Chemists at Rhone-Poulenc immediately went to work. To assess

a compound, they would give it to caged rats that had learned, upon

hearing the sound of a bell, to climb a rope to a resting platform in

order to avoid being shocked (the floor of the cage was electrified).

They knew they had found a successor to promethazine when they

injected compound 4560 RP into the rats: Not only were the rats

physically unable to climb the rope, they weren't emotionally inter¬

ested in doing so either. This new drug, chlorpromazine, apparently

disconnected brain regions that controlled both motor movement

and the mounting of emotional responses, and yet it did so without

causing the rats to lose consciousness.

Laborit tested chlorpromazine as part of a drug cocktail in surgi¬

cal patients in June of 1951. As expected, it put them into a "twi¬

light state.” Other surgeons tested it as well, reporting that it served

to "potentiate” the effects of the other anesthetic agents, the cock¬

tail inducing an "artificial hibernation." In December of that year,

Laborit spoke of this new advance in surgery at an anesthesiology

conference in Brussels, and there he made an observation that

suggested chlorpromazine might also be of use in psychiatry. It

"produced a veritable medicinal lobotomy," he said.*

Although today we think of lobotomy as a mutilating surgery, at

that time it was regarded as a useful operation. Only two years

earlier, the Nobel Prize in Medicine had been awarded to the Por¬

tuguese neurologist, Egas Moniz, who had invented it. The press, in

its most breathless moments, had even touted lobotomy as an oper¬

ation that plucked madness neatly from the mind. But what the

surgery most reliably did, and this was well understood by those

who performed the operation, was change people in a profound

way. It made them lethargic, disinterested, and childlike. That was

seen by the promoters of lobotomy as an improvement over what

the patients had been before —anxious, agitated, and filled with psy¬

chotic thoughts —and now, if Laborit was to be believed, a pill had

been discovered that could transform patients in a similar way.

In the spring of 1952, two prominent French psychiatrists, Jean

50 •

ANATOMY OF AN EPIDEMIC

Delay and Pierre Deniker, began administering chlorpromazine to

psychotic patients at St. Anne's Hospital in Paris, and soon use of

the drug spread to asylums throughout Europe. Everywhere the re¬

ports were the same: Hospital wards were quieter, the patients

easier to manage. Delay and Deniker, in a series of articles they

published in 1952, described the "psychic syndrome” induced by

chlorpromazine:

Seated or lying down, the patient is motionless on his bed,

often pale and with lowered eyelids. He remains silent most

of the time. If questioned, he responds after a delay, slowly, in

an indifferent monotone, expressing himself with few words

and quickly becoming mute. Without exception, the response

is generally valid and pertinent, showing that the subject is

capable of attention and of reflection. But he rarely takes the

initiative of asking a question; he does not express his preoc¬

cupations, desires, or preference. He is usually conscious of

the amelioration brought on by the treatment, but he does not

express euphoria. The apparent indifference or the delay of

the response to external stimuli, the emotional and affective

neutrality, the decrease in both initiative and preoccupation

without alteration in conscious awareness or in intellectual

faculties constitute the psychic syndrome due to the treat¬

ment. 5

U.S. psychiatrists dubbed chlorpromazine, which was marketed

in the United States as Thorazine, as a "major tranquilizer.” Back in

France, Delay and Deniker coined a more precise scientific term:

This new drug was a "neuroleptic,” meaning it took hold of the ner¬

vous system. Chlorpromazine, they concluded, induced deficits sim¬

ilar to those seen in patients ill with encephalitis lethargica. "In

fact," Deniker wrote, "it would be possible to cause true encephali¬

tis epidemics with the new drugs. Symptoms progressed from re¬

versible somnolence to all types of dyskinesia and hyperkinesia, and

finally to parkinsonism." 6 Physicians in the United States similarly

understood that this new drug was not fixing any known pathology.

"We have to remember that we are not treating diseases with this

PSYCHIATRY'S MAGIC BULLETS

drug," said psychiatrist E. H. Parsons, at a 1955 meeting in

Philadelphia on chlorpromazine. "We are using a neuropharma-

cologic agent to produce a specific effect." 7

At the same time that Rhone-Poulenc was testing phenothiazines

for their possible magic-bullet properties against malaria, Frank

Berger, a Czech-born chemist, was doing research of a somewhat

similar kind in London, and his work led, in 1955, to the introduc¬

tion of "minor tranquilizers” to the market.

During the war, Berger had been one of the scientists in Britain

who had helped develop methods to produce medically useful quan¬

tities of penicillin. But penicillin was effective only against gram¬

positive bacteria (microbes that took up a stain developed by

Danish scientist Hans Christian Gram), and after the war ended,

Berger sought to find a magic bullet that could kill gram-negative

microbes, the ones that caused a host of troubling respiratory, uri¬

nary, and gastrointestinal illnesses. At that time, there was a com¬

mercial disinfectant sold in Britain, called Phenoxetol, that was

advertised as effective against gram-negative bacteria in the envi¬

ronment, and Berger, who worked for British Drug Houses, Ltd.,

tinkered with the active ingredient in that product, a phenylglycerol

ether, in an effort to produce a product with superior antibacterial

effects. When a compound called mephenesin proved promising, he

gave it to mice to test its toxicity. "The compound, much to my sur¬

prise, produced reversible flaccid paralysis of the voluntary skeletal

muscles unlike that I had ever seen before,” Berger wrote. 8

Berger had stumbled on a potent muscle-relaxing agent. That

was curious enough, but what was even more surprising, the drug-

paralyzed mice didn't show any signs of being stressed by their new

predicament. He would put the animals on their backs and they

would be unable to right themselves, and yet their "heart beat was

regular, and there were no signs suggesting an involvement of the

autonomic nervous system.” The mice remained quiet and tranquil,

and Berger found that even when he administered low doses of this

amazing new compound to mice —the doses too small to cause mus¬

cle paralysis —they displayed this odd tranquility.

ANATOMY OF AN EPIDEMIC

Berger realized that a drug of this sort might have commercial

possibilities as an agent that allayed anxiety in people. However,

mephenesin was a very short-acting drug, providing only a few min¬

utes of peace. In 1947, Berger moved to the United States and went

to work for Wallace Laboratories in New Jersey, where he synthe¬

sized a compound, meprobamate, that lasted eight times as long in

the body as mephenesin. When Berger gave it to animals, he discov¬

ered that it also had powerful "taming” effects. "Monkeys after

being given meprobamate lost their viciousness and could be more

easily handled," he wrote. 9

Wallace Laboratories brought meprobamate to market in 1955,

selling it as Miltown. Other pharmaceutical companies scrambled

to develop competitor drugs, and as they did so, they looked for

compounds that would make animals less aggressive and numb to

pain. At Hoffmann-La Roche, chemist Leo Sternbach identified

chlordiazepoxide as having a "powerful and unique" tranquilizing

effect after he gave it to mice that ordinarily could be prompted to

fight by the application of electric shocks to their feet. 1 " Even with a

low dose of the drug, the mice remained noncombative when

shocked. This compound also proved to have potent taming effects

in larger animals —it turned tigers and lions into pussycats. The

final proof of chlordiazepoxide's merits involved another electric-

shock exam. Hungry rats were trained to press a lever for food, and

then they were taught that if they did so while a light in the cage

blinked on, they would be shocked. Although the rats quickly

learned not to press the lever while the light was on, they neverthe¬

less exhibited signs of extreme stress —defecating, etc.— whenever it

lit up their cage. But if they were given a dose of chlordiazepoxide?

The light would flash and they wouldn't be the least bit bothered.

Their "anxiety” had vanished, and they would even press the lever

to get something to eat, unworried about the shock to come.

Hoffmann-La Roche brought chlordiazepoxide to market in 1960,

selling it as Librium.

For obvious reasons, the public heard little about the animal tests

that had given rise to the minor tranquilizers. However, an article

published in the Science News Letter was the exception to the rule,

as its reporter put the animal experiments into a human frame of

PSYCHIATRY'S MAGIC BULLETS

reference. If you took a minor tranquilizer, he explained, "this

would mean that you might still feel scared when you see a car

speeding toward you, but the fear would not make you run." 11

Psychiatry now had a new drug for quieting hospitalized patients and

a second one for easing anxiety, the latter a drug that could be mar¬

keted to the general population, and by the spring of 1957, it gained

a medicine for depressed patients, iproniazid, which was marketed as

Marsilid. This drug, which was dubbed a "psychic energizer," could

trace its roots back to a poetically apt source: rocket fuel.

Toward the end of World War II, when Germany ran low on the

liquid oxygen and ethanol it used to propel its V-2 rockets, its scien¬

tists developed a novel compound, hydrazine, to serve as a substitute

fuel. After the war ended, chemical companies from the Allied coun¬

tries swooped in to grab samples of it, their pharmaceutical divi¬

sions eager to see if its toxic properties could be harnessed for

magic-bullet purposes. In 1951, chemists at Hoffmann-La Roche

created two hydrazine compounds, isoniazid and iproniazid, that

proved effective against the bacillus that caused tuberculosis. The

novel medicines were rushed into use in several TB hospitals, and

soon there were reports that the drug seemed to "energize” patients.

At Staten Island's Sea View Hospital, Time magazine reported, "pa¬

tients who had taken the drugs danced in the wards, to the delight

of news photographers." 12

The sight of TB patients doing a jig suggested that these drugs

might have a use in psychiatry as a treatment for depression. For

various reasons, iproniazid was seen as having the greater potential,

but initial tests did not find it to be particularly effective in lifting

spirits, and there were reports that it could provoke mania. Tuber¬

culosis patients treated with iproniazid were also developing so

many nasty side effects —dizziness, constipation, difficulty urinat¬

ing, neuritis, perverse skin sensations, confusion, and psychosis —

that its use had to be curtailed in sanitariums. However, in the

spring of 1957, Nathan Kline, a psychiatrist at Rockland State Hos¬

pital in Orangeburg, New York, rescued iproniazid with a report

that if depressed patients were kept on the drug long enough, for at

ANATOMY OF AN EPIDEMIC

least five weeks, it worked. Fourteen of the sixteen patients he'd

treated with iproniazid had improved, and some had a "complete

remission of all symptoms." 13

On April 7, 1957, the New York Times summed up iproniazid's

strange journey: "A side effect of an anti-tuberculosis drug may

have led the way to chemical therapy for the unreachable, severely

depressed mental patient. Its developers call it an energizer as

opposed to a tranquilizer." 14

Such were the drugs that launched the psychopharmacology revolu¬

tion. In the short span of three years (1954-1957), psychiatry

gained new medicines for quieting agitated and manic patients in

asylums, for anxiety, and for depression. But none of these drugs

had been developed after scientists had identified any disease

process or brain abnormality that might have been causing these

symptoms. They arrived out of the post-World War II search for

magic bullets against infectious diseases, with researchers, during

that process, stumbling on compounds that affected the central ner¬

vous system in novel ways. The animal tests of chlorpromazine,

meprobamate, and chlordiazepoxide revealed that these agents

sharply curbed normal physical and emotional responses, but did so

without causing a loss of consciousness. That was what was so

novel about the major and minor tranquilizers. They curbed brain

function in a selective manner. It was unclear how iproniazid

worked —it seemed to rev up the brain in some way —but, as the

New York Times had noted, its mood-lifting properties were prop¬

erly seen as a "side effect" of an anti-tuberculosis agent.

The drugs were best described as "tonics.” But in the media, a

story of a much different sort was being told.

An Unholy Alliance

The storytelling forces in American medicine underwent a profound

shift in the 1950s, and to see how that is so, we need to briefly

PSYCHIATRY'S MAGIC BULLETS

• 55

recount the history of the American Medical Association prior to

that time. At the turn of the century, the AMA set itself up as the or¬

ganization that would help the American public distinguish the

good from the bad. At that time, there were fifty thousand or so

medicinal products sold in the United States, and they were of two

basic types. There were thousands of small companies that sold

syrups, elixirs, and herbal remedies directly to the public (or as

packaged goods in stores), with these "patent" medicines typically

made from "secret" ingredients. Meanwhile, Merck and other

"drug houses" sold their chemical preparations, which were known

as "ethical" drugs, to pharmacists, who then acted as the retail ven¬

dors of these products. Neither group needed to prove to a govern¬

ment regulatory agency that its products were safe or effective, and

the AMA, eager to establish a place for doctors in this freewheeling

marketplace, set itself up as the organization that would do this as¬

sessment. It established a "propaganda department" to investigate

the patent medicines and thus protect Americans from "quackery,"

and it established a Council on Pharmacy and Chemistry to conduct

chemical tests of the ethical drugs. The AMA published the results

of these tests in its journals and provided the best ethical drugs with

its "seal of approval." The AMA also published each year a "useful

drugs” book, and its medical journals would not allow advertise¬

ments for any drug that had not passed its vetting process.

With this work, the AMA turned itself into a watchdog of the

pharmaceutical industry and its products. By doing so, the organi¬

zation was both providing a valuable service to the public and fur¬

thering its members' financial interests, for its drug evaluations

provided patients with a good reason to visit a doctor. A physician,

armed with his book of useful drugs, could prescribe an appropriate

one. And it was this knowledge, as opposed to any government-

authorized prescribing power, that provided physicians with their

value in the marketplace (in terms of providing access to medicines).

The selling of drugs in the United States began to change with the

passage of the 1938 Food and Drug Cosmetics Act. The law re¬

quired drug firms to prove to the Food and Drug Administration

that their products were safe (they still did not have to prove that

their drugs were helpful), and in its wake, the FDA began decreeing

5 6 •

ANATOMY OF AN EPIDEMIC

that certain medicines could be purchased only with a doctor's

prescription.* In 1951, Congress passed the Durham-Humphrey

Amendment to the act, which decreed that most new drugs would

be available by prescription only, and that prescriptions would be

needed for refills, too.

Physicians now enjoyed a very privileged place in American soci¬

ety. They controlled the public's access to antibiotics and other new

medicines. In essence, they had become the retail vendors of these

products, with pharmacists simply fulfilling their orders, and as

vendors, they now had financial reason to tout the wonders of their

products. The better the new drugs were perceived to be, the more

inclined the public would be to come to their offices to obtain a pre¬

scription. "It would appear that a physician's own market position

is strongly influenced by his reputation for using the latest drug,”

explained Fortune magazine. 15

The financial interests of the drug industry and physicians were

lined up in a way they never had been before, and the AMA

quickly adapted to this new reality. In 1952, it stopped publishing

its yearly book on "useful drugs." Next, it began allowing adver¬

tisements in its journals for drugs that had not been approved by

its Council on Pharmacy and Chemistry. In 1955, the AMA aban¬

doned its famed "seal of acceptance” program. By 1957, it had cut

the budget for its Council on Drugs to a paltry $75,000, which

was understandable, given that the AMA was no longer in the

business of assessing the merits of these products. Three years later,

the AMA even lobbied against a proposal by Tennessee senator

Estes Kefauver that drug companies prove to the FDA that their

new drugs were effective. The AMA, in its relationship to the phar¬

maceutical industry, had "become what I would call sissy,” con¬

fessed Harvard Medical School professor Maxwell Finland, in

testimony to Congress. 16

But it wasn't just that the AMA had given up its watchdog role.

The AMA and physicians were also now working with the

* In 1914, the Harrison Narcotics Act required a doctor's prescription for opi¬

ates and cocaine. The 1938 Food and Drug Cosmetics Act extended that

prescription-only requirement to a larger number of drugs.

PSYCHIATRY'S MAGIC BULLETS

pharmaceutical industry to promote new drugs. In 1951, the year

that the Durham-Humphrey Act was passed, Smith Kline and

French and the American Medical Association, began jointly pro¬

ducing a television program called The March of Medicine, which,

among other things, helped introduce Americans to the "wonder”

drugs that were coming to market. Newspaper and magazine arti¬

cles about new medications inevitably included testimonials from

doctors touting their benefits, and as Pfizer physician Haskell Wein¬

stein later confessed to a congressional committee, "much of what

appears [in the popular press] has in essence been placed by the

public relations staffs of the pharmaceutical firms." 17 In 1952, an

industry trade publication, FDC Reports, noted that the pharma¬

ceutical industry was enjoying a "sensationally favorable press,”

and a few years later, it commented on why this was so. "Virtually

all important drugs," it wrote, receive "lavish praise by the medical

profession on introduction." 18

This new marketplace for drugs proved profitable for all in¬

volved. Drug industry revenues topped $1 billion in 1957, the phar¬

maceutical companies enjoying earnings that made them "the

darlings of Wall Street," one writer observed. 18 Now that physicians

controlled access to antibiotics and all other prescription drugs,

their incomes began to climb rapidly, doubling from 1950 to 1970

(after adjusting for inflation). The AMA's revenues from drug ad¬

vertisements in its journals rose from $2.5 million in 1950 to $10

million in 1960, and not surprisingly, these advertisements painted

a rosy picture. A 1959 review of drugs in six major medical journals

found that 89 percent of the ads provided no information about the

drugs' side effects. 20

Such was the environment in the 1950s when the first psychiatric

drugs were brought to market. The public was eager to hear of

wonder drugs, and this was just the story that the pharmaceutical

industry and the nation's physicians were eager to tell.

ANATOMY OF AN EPIDEMIC

Miracle Pills

Smith Kline and French, which obtained a license from Rhone-

Poulenc to sell chlorpromazine in the United States, secured FDA

approval for Thorazine on March 26, 1954. A few days later, the

company used its March of Medicine show to launch the product.

Although Smith Kline and French had spent only $350,000 devel¬

oping Thorazine, having administered it to fewer than 150 psychi¬

atric patients prior to submitting its application to the FDA, the

company's president, Francis Boyer, told viewers that this was a

product that had gone through the most rigorous testing imagin¬

able. "It was administered to well over five thousand animals and

proved active and safe for human administration," he said. "We

then placed the compound in the hands of physicians in our great

American medical centers to explore its clinical value and possible

limitations. In all, over two thousand doctors in this country and

Canada have used it. . . . The development of a new medicine is dif¬

ficult and costly, but it is a job our industry is privileged to per¬

form." 21

Boyer's was a story of rigorous science at work, and less than

three months later, Time, in an article titled "Wonder Drug of

1954?", pronounced Thorazine a "star performer." After a dose of

Thorazine, the magazine explained, patients "sit up and talk sense

with [the doctor], perhaps for the first time in months." 22 In a

follow-up article, Time reported that patients "willingly took [the]

pills” and that once they did, they "fed themselves, ate heartily and

slept well.” Thorazine, the magazine concluded, was as important

"as the germ-killing sulfas discovered in the 1930s." 23

This was a magic-bullet reference that was impossible to miss,

and other newspapers and magazines echoed that theme. Thanks to

chlorpromazine, U.S. News and World Report explained, "patients

who were formerly untreatable within a matter of weeks or months

become sane, rational human beings." 24 The New York Times, in a

series of articles in 1954 and 1955, called Thorazine a "miracle” pill

that brought psychiatric patients "peace of mind” and "freedom

PSYCHIATRY’S MAGIC BULLETS

5 9

from confusion.” Thorazine, newspapers and magazines agreed,

had ushered in a "new era of psychiatry." 25

With such stories being told about Thorazine, it was little won¬

der that the public went gaga when Miltown, in the spring of 1955,

was introduced into the market. This drug, Time reported, was for

"walk-in neurotics rather than locked-in psychotics," and accord¬

ing to what psychiatrists were telling newspaper and magazine re¬

porters, it had amazing properties. 26 Anxiety and worries fled so

quickly, Changing Times explained, that it could be considered a

"happy pill." Reader's Digest likened it to a "Turkish bath in a

tablet.” The drug, explained Consumer Reports, "does not deaden

or dull the senses, and it is not habit forming. It relaxes the muscles,

calms the mind, and gives people a renewed ability to enjoy life." 22

The public rush to obtain this new drug was such that Wallace

Laboratories and Carter Products, which were jointly selling

meprobamate, struggled to keep up with the demand. Drugstores

lucky enough to have a supply put out signs that screamed: YES, WE

have miltown! The comedian Milton Berle said that he liked the

drug so much that he might change his first name to Miltown. Wal¬

lace Laboratories hired Salvador Dali to help stoke Miltown fever,

paying the great artist $35,000 to create an exhibit at an AMA

convention that was meant to capture the magic of this new drug.

Attendees walked into a darkened claustrophobic tunnel that repre¬

sented the interior of a caterpillar —this was what it was like to be

anxious —and then, as they emerged back into the light, they came

upon a golden "butterfly of tranquility," this metamorphosis due to

meprobamate. "To Nirvana with Miltown" is how Time described

Dali's exhibit. 28

There was one slightly hesitant note that appeared in newspaper

and magazine articles during the introduction of Thorazine and

Miltown. In the 1950s, many of the psychiatrists at top American

medical schools were Freudians, who believed that mental disorders

were caused by psychological conflicts, and their influence led Smith

Kline and French, in its initial promotion of Thorazine, to caution

reporters that "there is no thought that chlorpromazine is a cure for

mental illness, but it can have great value if it relaxes patients and

ANATOMY OF AN EPIDEMIC

6 o •

makes them accessible to treatment." 29 Both Thorazine and

Miltown, explained the New York Titties, should be considered as

"adjuncts to psychotherapy, not the cure." 30 Thorazine was called a

"major tranquilizer" and Miltown a "minor tranquilizer,” and

when Hoffmann-La Roche brought iproniazid to market, it was de¬

scribed as a "psychic energizer." These drugs, although they may

have been remarkable in kind, were not antibiotics for the mind. As

Life magazine noted in a 1956 article titled "The Search Has Only

Started,” psychiatry was still in the early stages of its revolution, for

the "bacteria” of mental disorders had yet to be discovered. 31

Yet, in very short order, even this note of caution went by the

wayside. In 1957, the New York Times reported that researchers

now believed that iproniazid might be a "potent regulator of unbal¬

anced cerebral metabolism." 32 This suggested that the drug, which

had been developed to fight tuberculosis, might be fixing something

that was wrong in the brains of depressed patients. A second drug

for depressed patients, imipramine, arrived on the market during

this time, and in 1959 the New York Times called them "anti¬

depressants" for the first time. Both appeared to "reverse psychic

states,” the paper said. 33 These drugs were gaining a new status, and

finally psychiatrist Harold Himwich, in a 1958 article in Science,

explained that they "may be compared with the advent of insulin,

which counteracts symptoms of diabetes." 34 The antidepressants

were fixing something wrong in the brain, and when Hoffmann-La

Roche brought Librium to market in 1960, it picked up on this cur¬

ative message. Its new drug was not just another tranquilizer, but

rather "the successor to this entire group. . . . Librium is the biggest

step yet toward 'pure' anxiety relief as distinct from central sedation

or hypnotic action." 33 Merck did the same, marketing its drug

Suavitil as "a mood normalizer. . . . Suavitil offers a new and spe¬

cific type of neurochemical treatment for the patient who is disabled

by anxiety, tension, depression, or obsessive-compulsive manifesta¬

tions." 36

The final step in this image makeover of the psychiatric drugs

came in 1963. The NIMH had conducted a six-week trial of Tho¬

razine and other neuroleptics, and after these drugs were shown to

be more effective than a placebo in knocking down psychotic

PSYCHIATRY'S MAGIC BULLETS

6 1

symptoms, the researchers concluded that that the drugs should be

regarded "as antischizophrenic in the broad sense. In fact, it is ques¬

tionable whether the term 'tranquilizer' should be retained." 3 '

With this pronouncement by the NIMH, the transformation of

the psychiatric drugs was basically complete. In the beginning, Tho¬

razine and other neuroleptics had been viewed as agents that made

patients quieter and emotionally indifferent. Now they were

"antipsychotic" medications. Muscle relaxants that had been devel¬

oped for use in psychiatry because of their "taming” properties

were now "mood normalizers." The psychic energizers were "anti¬

depressants." All of these drugs were apparently antidotes to spe¬

cific disorders, and in that sense, they deserved to be compared to

antibiotics. They were disease-fighting agents, rather than mere ton¬

ics. All that was missing from this story of magic-bullet medicine

was an understanding of the biology of mental disorders, but with

the drugs reconceived in this way, once researchers came to under¬

stand how the drugs affected the brain, they developed two

hypotheses that, at least in theory, filled in this gap.

Chemicals in the Brain

At the start of the 1950s, there was an ongoing debate among neuro¬

logists about how signals crossed the tiny synapses that separated

neurons in the brain. The prevailing view was that the signaling was

electrical in kind, but others argued for chemical transmission, a de¬

bate that historian Elliot Valenstein, in his book Blaming the Brain,

characterized as the "war between the sparks and the soups.” How¬

ever, by the mid-1950s, researchers had isolated a number of possi¬

ble chemical messengers in the brains of rats and other mammals,

including acetylcholine, serotonin, norepinephrine, and dopamine,

and soon the "soup” model had prevailed.

With that understanding in place, an investigator at the NIMH,

Bernard Brodie, planted the intellectual seed that grew into the

theory that depression was due to a chemical imbalance in the

brain. In 1955, in experiments with rabbits, Brodie reported that re-

ANATOMY OF AN EPIDEMIC

serpine, an herbal drug used in India to quiet psychotic patients,

lowered brain levels of serotonin. It also made the animals "lethar¬

gic" and "apathetic.” Arvid Carlsson, a Swedish pharmacologist

who had worked for a time in Brodie’s lab, soon reported that re-

serpine also reduced brain levels of norepinephrine and dopamine

(which jointly are known as catecholamines). Thus, a drug that

depleted serotonin, norepinephrine, and dopamine in the brain

seemed to make animals "depressed.” However, investigators dis¬

covered that if animals were pretreated with iproniazid or imi-

pramine before they were given reserpine, they didn't become

lethargic and apathetic. The two "antidepressants," in one manner

or another, apparently blocked reserpine's usual depletion of sero¬

tonin and the catecholamines. 38

During the 1960s, scientists at the NIMH and elsewhere figured

out how iproniazid and imipramine worked. The transmission of

signals from the "presynaptic” neuron to the "postsynaptic" neu¬

ron needs to be lightning fast and sharp, and in order for the signal

to be terminated, the chemical messenger must be removed from the

synapse. This is done in one of two ways. Either the chemical is me¬

tabolized by an enzyme and shuttled off as waste, or else it flows

back into the presynaptic neuron. Researchers discovered that ipro¬

niazid thwarts the first process. It blocks an enzyme, known as

monoamine oxidase, that metabolizes norepinephrine and sero¬

tonin. As a result, the two chemical messengers remain in the

synapse longer than normal. Imipramine inhibits the second

process. It blocks the "reuptake” of norepinephrine and serotonin

by the presynaptic neuron, and thus, once again, the two chemicals

remain in the synapse longer than normal. Both drugs produce a

similar end result, although they do so by different means.

In 1965, the NIMH's Joseph Schildkraut, in a paper published in

the Archives of General Psychiatry, reviewed this body of research

and set forth a chemical imbalance theory of affective disorders:

Those drugs [like reserpine] which cause depletion and

inactivation of norepinephrine centrally produce sedation or

depression, while drugs which increase or potentiate norepi¬

nephrine are associated with behavioral stimulation or excite-

PSYCHIATRY'S MAGIC BULLETS

merit and generally exert an antidepressant effect in man.

From these findings a number of investigators have formu¬

lated a hypothesis about the pathophysiology of the affective

disorders. This hypothesis, which has been designated the

"catecholamine hypothesis of affective disorders," proposes

that some, if not all depressions are associated with an ab¬

solute or relative deficiency of catecholamines, particularly

norepinephrine. 39

Although this hypothesis had its obvious limitations —it was,

Schildkraut said, "at best a reductionistic oversimplification of a

very complex biological state" —the first pillar in the construction

of the doctrine known today as "biological psychiatry" had been

erected. Two years later, researchers erected the second pillar: the

dopamine hypothesis of schizophrenia.

Evidence for this theory arose from investigations into Parkin¬

son's disease. In the late 1950s, Sweden's Arvid Carlsson and others

suggested that Parkinson's might be due to a deficiency in dopa¬

mine. To test this possibility, Viennese neuropharmacologist Oleh

Hornykiewicz applied iodine to the brain of a man who'd died from

the illness, as this chemical turns dopamine pink. The basal gan¬

glia, an area of the brain that controls motor movements, was

known to be rich in dopaminergic neurons, and yet in the basal

ganglia of the Parkinson's patient, there was "hardly a tinge of pink

discoloration," Hornykiewicz reported. 90

Psychiatric researchers immediately understood the possible rele¬

vance of this to schizophrenia. Thorazine and other neuroleptics reg¬

ularly induced Parkinsonian symptoms —the same tremors, tics, and

slowed gait. And if Parkinson's resulted from the death of dopamin¬

ergic neurons in the basal ganglia, then it stood to reason that anti¬

psychotic drugs, in some manner or another, thwarted dopamine

transmission in the brain. The death of dopaminergic neurons and

the blocking of dopamine transmission would both produce a

dopamine malfunction in the basal ganglia. Carlsson soon reported

that Thorazine and the other drugs for schizophrenia did just that.

This was a finding, however, that told of drugs that "discon¬

nected” certain brain regions. They weren't normalizing brain

ANATOMY OF AN EPIDEMIC

function; they were creating a profound pathology. However, at

this same time, researchers reported that amphetamines —drugs

known to trigger hallucinations and paranoid delusions —elevated

dopamine activity in the brain. Thus, it appeared that psychosis

might be caused by too much dopamine activity, which the neu¬

roleptics then curbed (and thus brought back into balance). If so,

the drugs could be said to be antipsychotic in kind, and in 1967,

Dutch scientist Jacques Van Rossum explicitly set forth the

dopamine hypothesis of schizophrenia. "When the hypothesis of

dopamine blockade by neuroleptic agents can be further substanti¬

ated, it may have fargoing consequences for the pathophysiology of

schizophrenia. Overstimulation of dopamine receptors could then

be part of the aetiology” of the disease. 41

Expectations Fulfilled

The revolution in mental health care that Congress had hoped for

when it created the NIMH twenty years earlier was now —or so it

seemed —complete. Psychiatric drugs had been developed that were

antidotes to biological disorders, and researchers believed that the

drugs worked by countering chemical imbalances in the brain. The

horrible mental hospitals that had so shamed the nation at the end

of World War II could now be shuttered, as schizophrenics —thanks

to the new drugs —could be treated in the community. Those suffer¬

ing from a milder disorder, like depression or anxiety, simply needed

to reach into their medicine cabinets for relief. In 1967, one in three

American adults filled a prescription for a "psychoactive” medica¬

tion, with total sales of such drugs reaching $692 million. 42

This was a narrative of a scientific triumph, and in the late 1960s

and early 1970s, the men who had been the pioneers in this new

field of "psychopharmacology" looked back with pride at their

handiwork. "It was a revolution and not just a transition period,”

said Frank Ayd Jr., editor of the International Drug Therapy

Newsletter. "There was an actual revolution in the history of

psychiatry and one of the most important and dramatic epics in the

PSYCHIATRY'S MAGIC BULLETS

history of medicine itself." 43 Roland Kuhn, who had "discovered"

imipramine, reasoned that the development of antidepressants

could properly be seen as "an achievement of the progressively

developing human intellect." 44 Anti-anxiety medicines, said Frank

Berger, the creator of Miltown, were "adding to happiness, human

achievement, and the dignity of man." 45 Such were the sentiments

of those who had led this revolution, and finally, at a 1970 sympo¬

sium on biological psychiatry in Baltimore, Nathan Kline summed

up what most of those in attendance understood to be true: They all

had earned a place in the pantheon of great medical men.

"Medicine and science will be just that much different because

we have lived," Kline told his colleagues. "Treatment and under¬

standing of [mental] illness will forever be altered . . . and in our

own way we will persist for all time in that small contribution we

have made toward the Human Venture." 46

A Scientific Revolution ... or a Societal Delusion?

Today, by retracing the discovery of the first generation of psychi¬

atric drugs and following their transformation into magic bullets,

we can see that by 1970 two possible histories were unfolding. One

possibility is that psychiatry, in a remarkably fortuitous turn of

events, had stumbled on several types of drugs that, although they

produced abnormal behaviors in animals, nevertheless fixed various

abnormalities in the brain chemistry of those who were mentally ill.

If so, then a true revolution was indeed under way, and we can ex¬

pect that when we review the long-term outcomes produced by

these drugs, we will find that they help people get well and stay

well. The other possibility is that psychiatry, eager to have its own

magic pills and eager to take its place in mainstream medicine,

turned the drugs into something they were not. These first-

generation drugs were simply agents that perturbed normal brain

function in some way, which is what the animal research had

shown, and if that is so, then it stands to reason that the long-term

outcomes produced by the drugs might be problematic in kind.

ANATOMY OF AN EPIDEMIC

Two possible histories were under way, and in the 1970s and

1980s, researchers investigated the critical question: Do people

diagnosed with depression and schizophrenia suffer from a chemi¬

cal imbalance that is then corrected by the medication? Were the

new drugs truly antidotes to something chemically amiss in the

brain?

The Hunt for Chemical Imbalances

The great tragedy of science—the slaying of a

beautiful hypothesis by an ugly fact."

-THOMAS HUXLEY (1870)'

The adult human brain weighs about three pounds, and when you

see it close up, removed from the skull, it is a bit larger than you

imagined it to be. I had thought a brain could rest fairly easily in the

palm of one's hand, but you really need both hands to lift it securely

into the air. If the brain is fresh, not yet pickled in formaldehyde, a

spiderweb of blood vessels pinkens the surface, and the tissue feels

soft, almost gelatinous. It is definitely "biological" in kind, and yet

somehow it gives rise to all of the mysterious and remarkable tal¬

ents of the human mind. At the invitation of a friend, Jang-Ho Cha,

who is a neuroscientist at Massachusetts General Hospital, I at¬

tended a brain-cutting seminar at the hospital, with the thought that

seeing a human brain would help me better visualize the neuro¬

transmitter pathways that are said to give rise to depression and

psychosis, but naturally my visit turned into something more than

that. The human brain up close takes your breath away.

The mechanics of its messaging system are fairly well under¬

stood. There are, Cha noted, 100 billion neurons in the human

brain. The cell body of a "typical" neuron receives input from a vast

web of dendrites, and it sends out a signal via a single axon that

may project to a distant area of the brain (or down the spinal cord).

At its end, an axon branches into numerous terminals, and it is from

ANATOMY OF AN EPIDEMIC

these terminals that chemical messengers —dopamine, serotonin,

etc.—are released into the synaptic cleft, which is a gap about

twenty nanometers wide (a nanometer is one-billionth of a meter).

A single neuron has between one thousand and ten thousand synap¬

tic connections, with the adult brain as a whole having perhaps 150

trillion synapses.

The axons of neurons that use the same neurotransmitter are

regularly bundled together, almost like the strands of a telecommu¬

nications cable, and once scientists discovered that dopamine,

norepinephrine, and serotonin fluoresced different colors when ex¬

posed to formaldehyde vapors, it became possible to track those

neurotransmitter pathways in the brain. Although Joseph Schild-

kraut, when he formulated his theory of affective disorders, thought

that norepinephrine was the neurotransmitter most likely to be in

short supply in those who were depressed, researchers fairly quickly

turned much of their attention to serotonin, and so for our pur¬

poses, in regard to our investigation of the chemical imbalance

theory of mental disorders, we need to look at that pathway in the

Serotonergic Pathways in the Brain

Cerebral cortex

Frontal

lobe

serotonergic

nerves

Basal ganglia

Temporal lobe

Hypothalamus

Raphe nuclei

(clusters

of cell

bodies of

serotonergic

nerves)

Pituitary

gland

To spinal cord

THE HUNT FOR CHEMICAL IMBALANCES

6 9

brain for depression, and at the dopaminergic pathway for schizo¬

phrenia.

The serotonergic pathway is one with ancient evolutionary roots.

Serotonergic neurons are found in the nervous systems of all verte¬

brates and most invertebrates, and in humans their cell bodies are

located in the brain stem, in an area known as the raphe nuclei.

Some of these neurons send long axons down the spinal cord, a sys¬

tem that is involved in the control of respiratory, cardiac, and gas¬

trointestinal activities. Other serotonergic neurons have axons that

ascend into all areas of the brain —the cerebellum, the hypothala¬

mus, the basal ganglia, the temporal lobes, the limbic system, the

cerebral cortex, and the frontal lobes. This pathway is involved in

Frontal

cortex

Mesocortical

system

Mesolimbic

system

Ventral

tegmental area

Substantia

nigra

Nigrostriatal

system

To basal

ganglia

Dopaminergic Pathways in the Brain

To striatum

ANATOMY OF AN EPIDEMIC

memory, learning, sleep, appetite, and the regulation of moods and

behaviors. As Efrain Azmitia, a professor of biology at NYU, has

noted, "the brain serotonin system is the single largest brain system

known and can be characterized as a 'giant' neuronal system." 2

There are three major dopaminergic pathways in the brain. The

cell bodies of all three systems are located atop the brain stem, in ei¬

ther the substantia nigra or the ventral tegmentum. Their axons

project to the basal ganglia (nigrostriatal system), the limbic region

(mesolimbic system), and the frontal lobes (mesocortical system).

The basal ganglia initiates and controls movement. The limbic

structures —the olfactory tubercle, the nucleus accumbens, and the

amygdala, among others —are located behind the frontal lobes and

help regulate our emotions. It is here that we feel the world, a

process that is vital to our sense of self and our conceptions of real¬

ity. The frontal lobes are the most distinguishing feature of the

human brain, and provide us with the godlike capacity to monitor

our own selves.

All of this physiology —the 100 billion neurons, the 150 trillion

synapses, the various neurotransmitter pathways —tell of a brain

that is almost infinitely complex. Yet the chemical imbalance theory

of mental disorders boiled this complexity down to a simple disease

mechanism, one easy to grasp. In depression, the problem was that

the serotonergic neurons released too little serotonin into the synap¬

tic gap, and thus the serotonergic pathways in the brain were "un¬

deractive." Antidepressants brought serotonin levels in the synaptic

gap up to normal, and that allowed these pathways to transmit mes¬

sages at a proper pace. Meanwhile, the hallucinations and voices

that characterized schizophrenia resulted from overactive dopamin¬

ergic pathways. Either the presynaptic neurons pumped out too

much dopamine into the synapse or the target neurons had an ab¬

normally high density of dopamine receptors. Antipsychotics put a

brake on this system, and this allowed the dopaminergic pathways

to function in a more normal manner.

That was the chemical imbalance theory put forth by Schildkraut

and Jacques Van Rossum, and the very research that had led

Schildkraut to his hypothesis also provided investigators with a

method for testing it. The studies of iproniazid and imipramine had

THE HUNT FOR CHEMICAL IMBALANCES

• 71

shown that neurotransmitters were removed from the synapse in

one of two ways. Either the chemical was taken back up into the

presynaptic neuron and restored for later use, or it was metabolized

by an enzyme and carted off as waste. Serotonin is metabolized

into 5-hydroxyindole acetic acid (5-HIAA); dopamine is turned

into homovanillic acid (HVA). Researchers could comb the cere¬

brospinal fluid for these metabolites, and the amounts found would

serve as an indirect gauge of the synaptic levels of the neurotrans¬

mitters. Since low serotonin was theorized to cause depression,

anyone in that emotional state should have lower-than-normal

levels of 5-HIAA in his or her cerebrospinal fluid. Similarly, since an

overactive dopamine system was theorized to cause schizophrenia,

people who heard voices or were paranoid should have abnormally

high cerebrospinal levels of HVA.

This line of research kept scientists busy for nearly fifteen years.

The Serotonin Hypothesis Is Put to the Test

In 1969, Malcolm Bowers at Yale University became the first to re¬

port on whether depressed patients had low levels of serotonin

metabolites in their cerebrospinal fluid. In a study of eight depressed

patients (all of whom had been previously exposed to antidepres¬

sants), he announced that their 5-HIAA levels were lower than nor¬

mal, but not "significantly" so. 3 Two years later, investigators at

McGill University said that they, too, had failed to find a "statisti¬

cally significant" difference in the 5-HIAA levels of depressed pa¬

tients and normal controls, and that they also had failed to find any

correlation between 5-HIAA levels and the severity of depressive

symptoms. 4 In 1974, Bowers was back with a more finely tuned

follow-up study: Depressed patients who had not been exposed to

antidepressants had perfectly normal 5-HIAA levels. 5

The serotonin theory of depression did not seem to be panning

out, and in 1974, two researchers at the University of Pennsylvania,

Joseph Mendels and Alan Frazer, revisited the evidence that had led

Schildkraut to advance his theory in the first place. Schildkraut had

ANATOMY OF AN EPIDEMIC

noted that reserpine, which depleted monoamines in the brain

(norepinephrine, serotonin, and dopamine), regularly made people

depressed. But when Mendels and Frazer looked closely at the scien¬

tific literature, they found that when hypertensive patients were

given reserpine, only 6 percent in fact got the blues. Furthermore, in

1955, a group of physicians in England had given the herbal drug to

their depressed patients, and it had lifted the spirits of many. Reser¬

pine, Mendels and Frazer concluded, didn't reliably induce depres¬

sion at all. 6 They also noted that when researchers had given other

monoamine-depleting drugs to people, those agents hadn't induced

depression either. "The literature reviewed here strongly suggests

that the depletion of brain norepinephrine, dopamine or serotonin

is in itself not sufficient to account for the development of the clini¬

cal syndrome of depression," they wrote.’

It seemed that the theory was about to be declared dead and

buried, but then, in 1975, Marie Asberg and her colleagues at the

Karolinska Institute in Stockholm breathed new life into it. Twenty

of the sixty-eight depressed patients they had tested suffered from

low 5-F1IAA levels, and these low-serotonin patients were some¬

what more suicidal than the rest, with two of the twenty eventually

committing suicide. This was evidence, the Swedish researchers

said, that there might be "a biochemical subgroup of depressive dis¬

order characterized by a disturbance of serotonin turnover." 8

Soon prominent psychiatrists in the United States were writing

that "nearly 30 percent" of depressed patients had been found to

have low serotonin levels. The serotonin theory of depression

seemed at least partly vindicated. But today, if we revisit Asberg's

study and examine her data, we can see that her finding of a "bio¬

logical subgroup” of depressed patients was mostly a story of wish¬

ful thinking.

In her study, Asberg reported that 25 percent of her "normal"

group had cerebrospinal 5-HIAA levels below fifteen nanograms

per milliliter. Fifty percent had fifteen to twenty-five nanograms of

5-HIAA per milliliter, and the remaining 25 percent had levels

above twenty-five nanograms. The bell curve for her "normals"

showed that 5-HIAA levels were quite variable. But what she failed

THE HUNT FOR CHEMICAL

MBALANCES

to note in her discussion was that the bell curve for the sixty-eight

depressed patients in her study was almost exactly the same.

Twenty-nine percent (twenty of the sixty-eight) had 5-HIAA counts

below fifteen nanograms, 47 percent had levels between fifteen and

twenty-five nanograms, and 24 percent had levels above twenty-five

nanograms. Twenty-nine percent of depressed patients may have

had "low” levels of serotonin metabolites in their cerebrospinal

fluid (this was her "biological subgroup"), but then so did 25

percent of "normal" people. The median level for normals was

twenty nanograms, and, it so turned out, more than half of the de¬

pressed patients —thirty-seven of sixty-eight —had levels above that

amount.

Viewed in this way, her study had not provided any new reason

to believe in the serotonin theory of depression. Japanese investiga¬

tors soon revealed, in an unwitting way, the faulty logic at work.

They reported that some antidepressants (used in Japan) blocked

serotonin receptors, inhibiting the firing of those pathways, and

thus they reasoned that depression might be caused by an "excess of

free serotonin in the synaptic cleft." 9 They had applied the same

backwards reasoning that had given rise to the low-serotonin the¬

ory of depression, and if the Japanese scientists had wanted to, they

could have pointed to Asberg's study for support of their theory, as

the Swedes had found that 24 percent of depressed patients had

"high" levels of serotonin.

In 1984, NIMH investigators studied the low-serotonin theory

of depression one more time. They wanted to see whether the "bio¬

logical subgroup” of depressed patients with "low” levels of sero¬

tonin were the best responders to an antidepressant, amitriptyline,

that selectively blocked its reuptake. If an antidepressant was an anti¬

dote to a chemical imbalance in the brain, then amitriptyline should

be most effective in that subgroup. But, lead investigator James

Maas wrote, "contrary to expectations, no relationships between

cerebrospinal 5-HIAA and response to amitriptyline were found." 10

Moreover, he and the other NIMH researchers discovered—just as

Asberg had —that 5-HIAA levels varied widely in depressed pa¬

tients. Some had high levels of serotonin metabolites in their cere-

74 • ANATOMY OF AN EPIDEMIC

brospinal fluid, while others had low levels. The NIMH scientists

drew the only possible conclusion: "Elevations or decrements in the

functioning of serotonergic systems per se are not likely to be

associated with depression."*

Even after this report, the serotonin theory of depression did not

completely go away. The commercial success of Prozac, a "selective

serotonin reuptake inhibitor” brought to market in 1988 by Eli

Lilly, fueled a new round of public claims that depression was due

to low levels of this neurotransmitter, and once again any number of

investigators conducted experiments to see if that were so. But this

second round of studies produced the same results as the first. "I

spent the first several years of my career doing full-time research on

brain serotonin metabolism, but I never saw any convincing evi¬

dence that any psychiatric disorder, including depression, results

from a deficiency of brain serotonin," said Stanford psychiatrist

David Burns in 2 003.“ Numerous others made this same point.

"There is no scientific evidence whatsoever that clinical depression

is due to any kind of biological deficit state,” wrote Colin Ross, an

associate professor of psychiatry at Southwest Medical Center in

Dallas, in his 1995 book, Pseudoscience in Biological Psychiatry. 11

In 2 000, the authors of Essential Psychopharmacology told medical

students "there is no clear and convincing evidence that monoamine

deficiency accounts for depression; that is, there is no 'real'

monoamine deficit." 13 Yet, fueled by pharmaceutical advertise¬

ments, the belief lived on, and it caused Irish psychiatrist David

Healy, who has written a number of books on the history of psychi-

* The NIMH researchers also looked at a number of other possible associa¬

tions between variable neurotransmitter levels and response to an antidepres¬

sant. They measured norepinephrine metabolites and dopamine metabolites;

they divided their depressed patients into bipolar and unipolar groups; and

they evaluated their response to two antidepressants, imipramine and

amitriptyline. They found mild associations between several of these sub¬

groups and their response to one or other of the drugs; I have focused here on

their findings regarding whether (a) depression is due to low levels of sero¬

tonin, and (b) if the subgroup of patients with low levels of serotonin responds

better to a drug that selectively blocks the reuptake of this neurotransmitter.

THE HUNT FOR CHEMICAL

MBALANCES

atry, to quip in 2005 that this theory needed to be put into the med¬

ical dustbin, where other such discredited theories can be found.

"The serotonin theory of depression," he wrote, with evident exas¬

peration, "is comparable to the masturbatory theory of insanity." 14

Dopamine Deja Vu

When Van Rossum set forth his dopamine hypothesis of schizo¬

phrenia, he noted that the first thing that investigators needed to do

was "further substantiate" that antipsychotic drugs did indeed

thwart dopamine transmission in the brain. This took some time,

but by 1975, Solomon Snyder at Johns Hopkins Medical School

and Philip Seeman at the University of Toronto had fleshed out how

the drugs achieved that effect. First, Snyder identified two distinct

types of dopamine receptors, known as D, and D., Next, both in¬

vestigators found that antipsychotics blocked 70 to 90 percent of

the D 2 receptors. 15 Newspapers now told of how these drugs might

be correcting a chemical imbalance in the brain.

"Too much dopamine function in the brain could account for the

overwhelming flood of sensations that plagues the schizophrenic,”

the New York Times explained. "By blocking the brain's receptor

sites for dopamine, neuroleptics put an end to sights and sounds

that are not really there." 16

However, even as Snyder and Seeman were reporting their re¬

sults, Malcolm Bowers was announcing findings that cast a cloud

over the dopamine hypothesis. He had measured the level of

dopamine metabolites in the cerebrospinal fluid of unmedicated

schizophrenics and found them to be quite normal. "Our findings,"

he wrote, "do not furnish neurochemical evidence for an over¬

arousal in these patients emanating from a midbrain dopamine sys¬

tem.” 17 Others soon reported similar results. In 1975, Robert Post

at the NIMH determined that HVA levels in the cerebrospinal fluid

of twenty unmedicated schizophrenics "were not significantly dif¬

ferent from controls." 16 Autopsy studies also revealed that the brain

tissue of drug-free schizophrenics did not have abnormal levels of

ANATOMY OF AN EPIDEMIC

dopamine. In 1982, UCLA's John Haracz reviewed this body of

research and drew the obvious bottom-line conclusion: "These

findings do not support the presence of elevated dopamine turnover

in the brains of [unmedicated] schizophrenics." 19

Having discovered that dopamine levels in never-medicated

schizophrenics were normal, researchers turned their attention to a

second possibility. Perhaps people with schizophrenia had an over¬

abundance of dopamine receptors. If so, the postsynaptic neurons

would be "hypersensitive” to dopamine, and this would cause the

dopaminergic pathways to be overstimulated. In 1978, Philip See-

man at the University of Toronto announced in Nature that this was

indeed the case. At autopsy, the brains of twenty schizophrenics had

70 percent more Di receptors than normal. At first glance, it seemed

that the cause of schizophrenia had been found, but Seeman cau¬

tioned that all of the patients had been on neuroleptics prior to their

deaths. "Although these results are apparently compatible with the

dopamine hypothesis of schizophrenia in general," he wrote, the in¬

crease in D 2 receptors might "have resulted from the long-term ad¬

ministration of neuroleptics." 20

A variety of studies quickly proved that the drugs were indeed the

culprit. When rats were fed neuroleptics, their Dj receptors quickly

increased in number. 21 If rats were given a drug that blocked D, re¬

ceptors, that receptor subtype increased in density. 22 In each in¬

stance, the increase was evidence of the brain trying to compensate

for the drug's blocking of its signals. Then, in 1982, Angus MacKay

and his British colleagues reported that when they examined brain

tissue from forty-eight deceased schizophrenics, "the increases in

[Di] receptors were seen only in patients in whom neuroleptic medi¬

cation had been maintained until the time of death, indicating that

they were entirely iatrogenic [drug-caused]." 23 A few years later,

German investigators reported the same results from their autopsy

studies. 24 Finally, investigators in France, Sweden, and Finland used

positron emission topography to study D,-receptor densities in liv¬

ing patients who had never been exposed to neuroleptics, and all re¬

ported "no significant differences" between the schizophrenics and

"normal controls." 25

THE HUNT FOR CHEMICAL

MBALANCES

Since that time, researchers have continued to study whether

there might be something amiss with the dopaminergic pathways in

people diagnosed with schizophrenia, and now and then someone

reports having found an abnormality of some type in a subset of pa¬

tients. But by the end of the 1980s, it was clear that the chemical-

imbalance hypothesis of schizophrenia —that this was a disease

characterized by a hyperactive dopamine system that was then put

somewhat back into balance by the drugs —had come to a crashing

end. "The dopaminergic theory of schizophrenia retains little credi¬

bility for psychiatrists," observed Pierre Deniker in 1990. 2 ' Four

years later, John Kane, a well-known psychiatrist at Long Island

Jewish Medical Center, echoed the sentiment, noting that there

was "no good evidence for any perturbation of the dopamine func¬

tion in schizophrenia." 27 Still, the public continued to be told that

people diagnosed with schizophrenia had overactive dopamine sys¬

tems, with the drugs likened to "insulin for diabetes,” and thus for¬

mer NIMH director Steve Hyman, in his 2002 book, Molecular

Neuropharmacology, was moved to once again remind readers of

the truth. "There is no compelling evidence that a lesion in the

dopamine system is a primary cause of schizophrenia,” he wrote. 2 '

Requiem for a Theory

The low-serotonin hypothesis of depression and the high-dopamine

hypothesis of schizophrenia had always been the twin pillars of the

chemical-imbalance theory of mental disorders, and by the late

1980s, both had been found wanting. Other mental disorders have

also been touted to the public as diseases caused by chemical imbal¬

ances, but there was never any evidence to support those claims.

Parents were told that children diagnosed with attention deficit

hyperactivity disorder suffered from low dopamine levels, but the

only reason they were told that was because Ritalin stirred neurons

to release extra dopamine. This became the storytelling formula

that was relied upon by pharmaceutical companies again and again:

ANATOMY OF AN EPIDEMIC

Researchers would identify the mechanism of action for a class of

drugs, how the drugs either lowered or raised levels of a brain neuro¬

transmitter, and soon the public would be told that people treated

with those medications suffered from the opposite problem.

From a scientific point of view, it is apparent today that the

chemical imbalance hypothesis was always wobbly in kind, and

many of the scientists who watched its rise and fall have looked

back on it with a bit of embarrassment. As early as 1975, Joseph

Mendels and Alan Frazer had concluded that Schildkraut's hypoth¬

esis of depression had arisen out of "tunnel thinking” that relied on

an "inadequate evaluation of certain findings not consistent with

the initial assumption." 2 ’ In 1990, Deniker said that the same was

true of the dopamine hypothesis of schizophrenia. When psychiatric

researchers recast the drugs as "antischizophrenic” agents, he

noted, they had gone "a bit far . . . one can say that neuroleptics di¬

minish certain phenomena of schizophrenia, but [the drugs] do not

pretend to be an etiological treatment of these psychoses." 30 The

chemical-imbalance theory of mental disorders, wrote David Flealy,

in his book The Creation of Psychopharmacology, was embraced by

psychiatrists because it "set the stage” for them "to become real

doctors." 31 Doctors in internal medicine had their antibiotics, and

now psychiatrists could have their "anti-disease" pills too.

Yet a societal belief in chemical imbalances has remained (for rea¬

sons that will be explored later), and it has led those who have in¬

vestigated and written about this history to emphasize, time and

again, the same bottom-line conclusion. "The evidence does not sup¬

port any of the biochemical theories of mental illness,” concluded

Elliot Valenstein, a professor of neuroscience at the University of

Michigan, in his 1998 book Blaming the Brain. 32 Even U.S. surgeon

general David Satcher, in his 1999 report Mental Health, confessed

that "the precise causes [etiologies] of mental disorders are not

known." 33 In Prozac Backlash, Joseph Glenmullen, an instructor of

psychiatry at Harvard Medical School, noted that "in every instance

where such an imbalance was thought to be found, it was later

proved to be false." 34 Finally, in 2005, Kenneth Kendler, coeditor in

chief of Psychological Medicine, penned an admirably succinct

epitaph for this whole story: "We have hunted for big simple

THE HUNT FOR CHEMICAL

MBALANCES

neurochemical explanations for psychiatric disorders and have not

found them." 35

This brings us to our next big question: If psychiatric drugs don't

fix abnormal brain chemistry, what do they do?

Prozac on My Mind

During the 1970s and 1980s, investigators put together detailed ac¬

counts of how the various classes of psychiatric drugs act on the

brain, and how the brain in turn reacts to the drugs. We could relate

the history of antidepressants, neuroleptics, benzodiazepines, or

stimulants, and all of those histories would tell of a somewhat com¬

mon process at work. But since the story of chemical imbalances in

the public mind really took off after Eli Lilly brought Prozac (fluox¬

etine) to market, it seems appropriate to review what Eli Lilly

scientists and other investigators, in reports published in scientific

journals, had to say about how this "selective serotonin reuptake

inhibitor" actually worked.

As was noted earlier, once a presynaptic neuron has released

serotonin into the synaptic gap, it must be quickly removed so that

the signal can be crisply terminated. An enzyme metabolizes a small

amount; the rest is pumped back into the presynaptic neuron, enter¬

ing via a channel known as SERT (serotonin reuptake transport).

Fluoxetine blocks this reuptake channel, and as a result, Eli Lilly

scientist James Clemens wrote in 1975, it causes a "pile-up of sero¬

tonin at the synapse." 36

However, as the Eli Lilly investigators discovered, a feedback

mechanism then kicks in. The presynaptic neuron has "auto-

receptors" on its terminal membrane that monitor the level of

serotonin in the synapse. If serotonin levels are too low, one scientist

quipped, these autoreceptors scream "turn on the serotonin ma¬

chine.” If serotonin levels are too high, they scream "turn it off."

This is a feedback loop designed by evolution to keep the serotoner¬

gic system in balance, and fluoxetine triggers the latter message.

With serotonin no longer being whisked away from the synapse, the

ANATOMY OF AN EPIDEMIC

autoreceptors tell the presynaptic neurons to fire at a dramatically

lower rate. They begin to release lower-than-normal amounts of

serotonin into the synapse.

Feedback mechanisms also change the postsynaptic neurons.

Within four weeks, the density of their serotonin receptors drops 25

percent below normal, Eli Lilly scientists reported in 1981. 33 Other

investigators subsequently reported that "chronic fluoxetine treat¬

ment" may lead to a 50 percent reduction in serotonin receptors in

certain areas of the brain. 38 As a result, the postsynaptic neurons be¬

come "desensitized” to the chemical messenger.

At this point, it may seem that the brain has successfully adapted

to the drug. Fluoxetine blocks the normal reuptake of serotonin

from the synapse, but the presynaptic neurons then begin releasing

less serotonin and the postsynaptic neurons become less sensitive to

serotonin and thus don't fire so readily. The drug was designed to

accelerate the serotonergic pathway; the brain responded by putting

on the brake. It has kept its serotonergic pathway more or less in

balance, an adaptive response that researchers have dubbed "synap¬

tic resilience." 35 However, there is one other change that occurs dur¬

ing this initial two-week period, and it ultimately short-circuits the

brain's compensatory response. The autoreceptors for serotonin on

the presynaptic neurons decline in number. As a result, this feed¬

back mechanism becomes partially disabled, and the "turn off the

serotonin machine” message dims. The presynaptic neurons begin

to fire at a normal rate again, at least for a while, and to release

more serotonin than normal each time.* 40

As the Eli Lilly scientists and others put together this picture of

fluoxetine's effects on the brain, they speculated as to what part of

this process was responsible for the drug’s antidepressant proper¬

ties. Psychiatrists had long observed that antidepressants took two

or three weeks to "work,” and thus the Eli Lilly researchers rea¬

soned in 1981 that it was the decline in serotonin receptors, which

took several weeks to occur, that was "the underlying mechanism

associated with the therapeutic response." 41 If so, the drug could be

* Over the long term, it appears that serotonin release falls to an abnormally

low level, at least in certain regions of the brain.

THE HUNT FOR CHEMICAL IMBALANCES

said to work because it drove the serotonergic system into a less

responsive state. But once researchers discovered that fluoxetine

partially disabled the feedback mechanism, Claude de Montigny at

McGill University argued that this was what allowed the drug to

begin working. This disabling process also took two or three weeks

to occur, and it allowed the presynaptic neurons to begin pumping

higher amounts of serotonin than normal into the synapse. At that

point, with fluoxetine continuing to block serotonin's removal, the

neurotransmitter could now indeed "pile up” in the synapse, and

that would lead "to an enhancement of central serotonergic neuro¬

transmission," de Montigny wrote. 42

That is the scientific story of how fluoxetine alters the brain, and

it may be that this process helps depressed people get well and stay

well. Only the outcomes literature can reveal whether that is so. But

the medicine clearly doesn't fix a chemical imbalance in the brain.

Instead, it does precisely the opposite. Prior to being medicated, a

depressed person has no known chemical imbalance. Fluoxetine

then gums up the normal removal of serotonin from the synapse,

and that triggers a cascade of changes, and several weeks later the

serotonergic pathway is operating in a decidedly abnormal manner.

The presynaptic neuron is putting out more serotonin than usual.

Its serotonin reuptake channels are blocked by the drug. The sys¬

tem's feedback loop is partially disabled. The postsynaptic neurons

are "desensitized” to serotonin. Mechanically speaking, the sero¬

tonergic system is now rather mucked up.

Eli Lilly's scientists were well aware that this was so. In 1977,

Ray Fuller and David Wong observed that fluoxetine, since it dis¬

rupted serotonergic pathways, could be used to study "the role of

serotonin neurons in various brain functions —behavior, sleep, reg¬

ulation of pituitary hormone release, thermoregulation, pain re¬

sponsiveness and so on." To conduct such experiments, researchers

could administer fluoxetine to animals and observe which functions

became compromised. They would look for pathologies to appear.

This type of research in fact was already being done: Fuller and

Wong reported in 1977 that the drug stirred "stereotyped hyper¬

activity" in rats and "suppressed REM sleep” in both rats and

cats. 43

ANATOMY OF AN EPIDEMIC

In 1991, in a paper published in the Journal of Clinical Psychia¬

try, Princeton neuroscientist Barry Jacobs made this very point

about SSRIs. He wrote:

These drugs "alter the level of synaptic transmission beyond

the physiologic range achieved under [normal] environmen¬

tal/biological conditions. Thus, any behavioral or physiologic

change produced under these conditions might more appro¬

priately be considered pathologic, rather than reflective of the

normal biological role of 5-HT [serotonin.]” 44

During the 1970s and 1980s, researchers studying the effects of

neuroleptics fleshed out a similar story. Thorazine and other

standard antipsychotics block 70 to 90 percent of all D, receptors in

the brain. In response, the presynaptic neurons begin pumping out

more dopamine and the postsynaptic neurons increase the density

of their D= receptors by 30 percent or more. In this manner, the

brain is trying to "compensate” for the drug's effects so that it can

maintain the transmission of messages along its dopaminergic path¬

ways. However, after about three weeks, the pathway's feedback

mechanism begins to fail, and the presynaptic neurons begin to fire

in irregular patterns or turn quiescent. It is this "inactivation" of

dopaminergic pathways that "may be the basis for the antipsychotic

action," explains the American Psychiatric Association's Textbook

of Psychopharmacology. 15

Once again, this is a story of neurotransmitter pathways that

have been transformed by the medication. After several weeks, their

feedback loops are partially disabled, the presynaptic neurons are

releasing less dopamine than normal, the drug is thwarting

dopamine's effects by blocking D: receptors, and the postsynaptic

neurons have an abnormally high density of these receptors. The

drugs do not normalize brain chemistry, but disturb it, and if

Jacob's reasoning is followed, to a degree that could be considered

"pathological."

THE HUNT FOR CHEMICAL IMBALANCES • 83

A Paradigm for Understanding Psychotropic Drugs

Today, as provost of Harvard University, Steve Hyman is mostly en¬

gaged in the many political and administrative tasks that come with

leading a large institution. But he is a neuroscientist by training, and

in 1996 to 2001, when he was the director of the NIMH, he wrote

a paper, one both memorable and provocative in kind, that summed

up all that had been learned about psychiatric drugs. Titled "Initia¬

tion and Adaptation: A Paradigm for Understanding Psychotropic

Drug Action," it was published in the American Journal of Psychia¬

try, and it told of how all psychotropic drugs could be understood

to act on the brain in a common way. 46

Antipsychotics, antidepressants, and other psychotropic drugs,

he wrote, "create perturbations in neurotansmitter functions.” In

response, the brain goes through a series of compensatory adapta¬

tions. If a drug blocks a neurotransmitter (as an antipsychotic does),

the presynaptic neurons spring into hyper gear and release more of

it, and the postsynaptic neurons increase the density of their recep¬

tors for that chemical messenger. Conversely, if a drug increases the

synaptic levels of a neurotransmitter (as an antidepressant does), it

provokes the opposite response: The presynaptic neurons decrease

their firing rates and the postsynaptic neurons decrease the density

of their receptors for the neurotransmitter. In each instance, the

brain is trying to nullify the drug's effects. "These adaptations,”

Hyman explained, "are rooted in homeostatic mechanisms that

exist, presumably, to permit cells to maintain their equilibrium in

the face of alterations in the environment or changes in the internal

milieu.”

However, after a period of time, these compensatory mechanisms

break down. The "chronic administration" of the drug then causes

"substantial and long-lasting alterations in neural function,"

Hyman wrote. As part of this long-term adaptation process, there

are changes in intracellular signaling pathways and gene expression.

After a few weeks, he concluded, the person's brain is functioning in

a manner that is "qualitatively as well as quantitatively different

from the normal state.”

84. ANATOMY OF AN EPIDEMIC

His was an elegant paper, and it summed up what had been

learned from decades of impressive scientific work. Forty years ear¬

lier, when Thorazine and the other first-generation psychiatric drugs

were discovered, scientists had little understanding of how neurons

communicated with one another. Now they had a remarkably de¬

tailed understanding of neurotransmitter systems in the brain and

of how drugs acted on them. And what science had revealed was

this: Prior to treatment, patients diagnosed with schizophrenia, de¬

pression, and other psychiatric disorders do not suffer from any

known "chemical imbalance.” However, once a person is put on a

psychiatric medication, which, in one manner or another, throws a

wrench into the usual mechanics of a neuronal pathway, his or her

brain begins to function, as Hyman observed, abnormally.

Back to the Beginning

While Dr. Hyman's paper may seem startling, it serves as a coda to

a scientific narrative that is, in fact, consistent from beginning to

end. His was not a conclusion that should be seen as unexpected,

but rather one that was predicted by psychopharmacology's open¬

ing chapter.

As we saw, Thorazine, Miltown, and Marsilid were all derived

from compounds that had been developed for other purposes —for

use in surgery or as possible "magic bullets" against infectious dis¬

eases. Those compounds were then found to cause alterations in

mood, behavior, and thinking that were seen as helpful to psychi¬

atric patients. The drugs, in essence, were perceived as having bene¬

ficial side effects. They perturbed normal function, and that

understanding was reflected in the initial names given to them.

Chlorpromazine was a "major tranquilizer,” and it was said to pro¬

duce a change in being similar to frontal lobotomy. Meprobamate

was a "minor tranquilizer," and in animal studies, it had been

shown to be a powerful muscle relaxant that blocked normal emo¬

tional response to environmental stressors. Iproniazid was a "psy¬

chic stimulator,” and if the report of TB patients dancing in the

THE HUNT FOR CHEMICAL

MBALANCES

wards was truthful, it was a drug that could provoke something

akin to mania. However, psychiatry then reconceived the drugs as

"magic bullets" for mental disorders, the drugs hypothesized to be

antidotes to chemical imbalances in the brain. But that theory,

which arose as much from wishful thinking as from science, was

investigated and it did not pan out. Instead, as Hyman wrote, psy-

chotropics are drugs that perturb the normal functioning of

neuronal pathways in the brain. Psychiatry's first impression of its

new drugs turned out to be the scientifically accurate one.

With this understanding of psychiatric medications now in mind,

it is possible to pose the scientific question at the heart of this book:

Do these drugs help or harm patients over the long term? What do

fifty years of outcomes research show?

Part Three

Outcomes

A Paradox Revealed

"If we wish to base psychiatry on evidence-based

medicine, we run a genuine risk in taking a closer

look at what has long been considered fact."

-EMMANUEL STIP, EUROPEAN PSYCHIATRY (2002)'

The basement in Harvard Medical School's Countway Library is

one of my favorite places in Boston. After stepping off the elevator,

you enter a huge, somewhat dingy room, filled with the musty smell

of old books. I often stop a few feet inside the doorway and take in

the grand sight: row after row of bound copies of medical journals

from the early 1800s to 1986. The place is almost always empty,

and yet there are rich histories to be discovered here, and soon, as

you begin to piece together a particular narrative of medicine, you

are hopping from one journal to the next, the pile of books on your

desk growing ever higher. There is the thrill of the chase, and it

seems too that this part of the library never disappoints. All of the

journals are organized in alphabetical order, and whenever in one

article you find a citation that interests you, all you have to do is

walk a few feet and inevitably you find the journal you need. At

least up until recently, the Countway Library seems to have pur¬

chased nearly every medical journal that was published.

This is where we can begin our quest to find out how psychiatric

drugs affect long-term outcomes. The research method we'll need to

follow is straightforward. First, to the best we can, we'll have to

flesh out the natural spectrum of outcomes for each particular dis¬

order. In the absence of antipsychotic medications, how would peo-

ANATOMY OF AN EPIDEMIC

pie diagnosed with schizophrenia likely fare over time? What

chance —if any —would they have of recovering? How well might

they fare in society? The same questions can be asked in regard to

anxiety, depression, and bipolar illness. What would outcomes look

like in the absence of anti-anxiety drugs, antidepressants, and mood

stabilizers? Once we have a sense of a baseline for a disorder, we

can trace the outcomes literature for that illness, and we can hope

that it will tell a consistent, coherent story. Do the drug treatments

alter the long-term course of a mental disorder —in the patient pop¬

ulation as a whole —for the better? Or for the worse?

Since chlorpromazine (Thorazine) was the drug that launched the

psychopharmacology revolution, it seems appropriate to investigate

schizophrenia outcomes first.

The Natural History of Schizophrenia

Schizophrenia today is regularly thought of as a lifelong, chronic ill¬

ness, and that is an understanding that originated with the work of

German psychiatrist Emil Kraepelin. In the late 1800s, he systemat¬

ically tracked the outcomes of patients at an asylum in Estonia, and

he observed that there was an identifiable group that reliably deteri¬

orated into dementia. These were patients who, upon entry to the

asylum, showed a lack of emotion. Many were catatonic, or lost

hopelessly in their own worlds, and they often had gross physical

problems. They walked oddly, suffered from facial tics and muscle

spasms, and were unable to complete willed physical acts. In his

1899 textbook Lehrbuch der Psychiatrie, Kraepelin wrote that

these patients suffered from dementia praecox, and in 1908, Swiss

psychiatrist Eugen Bleuler coined the term "schizophrenia” as a

substitute diagnostic term for patients in this dilapidated condition.

However, as British historian Mary Boyle convincingly argued in

a 1990 article, "Is Schizophrenia What It Was? A Re-analysis of

Kraepelin's and Bleuler's Population,” many of Kraepelin's demen¬

tia praecox patients were undoubtedly suffering from a viral dis¬

ease, encephalitis lethargica, which in the late 1800s had yet to be

A PARADOX REVEALED

identified. This disease caused people to turn delirious, or to drop

into a stupor, or to start walking in a jerky manner, and once Aus¬

trian neurologist Constantin von Economo described the illness in

1917, the encephalitis lethargica patients were no longer part of the

"schizophrenia” pool, and after that happened, the patient group

that remained was quite different from Kraepelin's dementia prae-

cox group. "The inaccessible, the stuporous catatonic, the intellec¬

tually deteriorated” —those types of schizophrenia patients, Boyle

noted, largely disappeared. As a result, the descriptions of schizo¬

phrenia in psychiatric textbooks during the 1920s and 1930s

changed. All of the old physical symptoms —the greasy skin, the

odd gait, the muscle spasms, the facial tics —disappeared from the

diagnostic manuals. What remained were the mental symptoms —

the hallucinations, the delusions, and the bizarre thoughts. "The

referents of schizophrenia," Boyle wrote, "gradually changed until

the diagnosis came to be applied to a population who bore only a

slight, and possibly superficial, resemblance to Kraepelin's." 2

So now we have to ask: What is the natural spectrum of out¬

comes for that group of psychotic patients? Here, unfortunately, we

run into a second problem. From 1900 until the end of World War

II, eugenic attitudes toward the mentally ill were quite popular in

the United States, and that social philosophy dramatically affected

their outcomes. Eugenicists argued that the mentally ill needed to be

sequestered in hospitals to keep them from having children and

spreading their "bad genes.” The goal was to keep them confined in

asylums, and in 1923, an editorial in the Journal of Heredity con¬

cluded, with an air of satisfaction, that "segregation of the insane is

fairly complete." 3 As a result, many people diagnosed with schizo¬

phrenia in the first half of the century were hospitalized and never

discharged, but that social policy was then misperceived as out¬

comes data. The fact that schizophrenics never left the hospital was

seen as proof that the disease was a chronic, hopeless illness.

However, after World War II, eugenics fell into disrepute. This

was the very "science” that Hitler and Nazi Germany had em¬

braced, and after Albert Deutsch's expose of the abysmal conditions

in U.S. mental hospitals, in which he likened them to concentration

camps, many states began talking about treating the mentally ill in

ANATOMY OF AN EPIDEMIC

the community. Social policy changed and discharge rates soared.

As a result, there is a brief window of time, from 1946 to 1954,

when we can look at how newly diagnosed schizophrenia patients

fared and thereby get a sense of the "natural outcomes" of schizo¬

phrenia prior to the arrival of Thorazine.*

Here's the data. In a study conducted by the NIMH, 62 percent

of first-episode psychotic patients admitted to Warren State Hospi¬

tal in Pennsylvania from 1946 to 1950 were discharged within

twelve months. At the end of three years, 73 percent were out of the

hospital. 4 A study of 216 schizophrenia patients admitted to Dela¬

ware State Hospital from 1948 to 1950 produced similar results.

Eighty-five percent were discharged within five years, and on January

1, 1956 —six years or more after initial hospitalization —70 percent

were successfully living in the community. 5 Meanwhile, Hillside

Hospital in Queens, New York, tracked 87 schizophrenia patients

discharged in 1950 and determined that slightly more than half

never relapsed in the next four years. 6 During this period, outcomes

studies in England, where schizophrenia was more narrowly defined,

painted a similarly encouraging picture: Thirty-three percent of the

patients enjoyed a "complete recovery," and another 20 percent a

"social recovery," which meant they could support themselves and

live independently. 7

These studies provide a rather startling view of schizophrenia

outcomes during this time. According to the conventional wisdom,

it was Thorazine that made it possible for people with schizophre¬

nia to live in the community. But what we find is that the majority

of people admitted for a first episode of schizophrenia during the

late 1940s and early 1950s recovered to the point that within the

first twelve months, they could return to the community. By the end

of three years, that was true for 75 percent of the patients. Only a

small percentage —20 percent or so —needed to be continuously

hospitalized. Moreover, those returning to the community weren't

* During this period, schizophrenia was a diagnosis being broadly applied to

those being hospitalized. Many of these patients would be diagnosed as bipolar

or schizoaffective today. Still, this was the diagnosis for the most "seriously

disturbed" people in American society at that time.

A PARADOX REVEALED

living in shelters and group homes, as facilities of that sort didn't yet

exist. They were not receiving federal disability payments, as the SSI

and SSDI programs had yet to be established. Those discharged

from hospitals were mostly returning to their families, and judging

by the social recovery data, many were working. All in all, there

was reason for people diagnosed with schizophrenia during that

postwar period to be optimistic that they could get better and func¬

tion fairly well in the community.

It is also important to note that the arrival of Thorazine did not

improve discharge rates in the 1950s for people newly diagnosed

with schizophrenia, nor did its arrival trigger the release of chronic

patients. In 1961, the California Department of Mental Hygiene re¬

ported on discharge rates for all 1,413 first-episode schizophrenia

patients hospitalized in 1956, and it found that 88 percent of those

who weren't prescribed a neuroleptic were discharged within eigh¬

teen months. Those treated with a neuroleptic —about half of the

1,413 patients —had a lower discharge rate; only 74 percent were

discharged within eighteen months. This is the only large-scale study

from the 1950s that compared discharge rates for first-episode pa¬

tients treated with and without drugs, and the investigators con¬

cluded that "drug-treated patients tend to have longer periods of

hospitalization. . . . The untreated patients consistently show a

somewhat lower retention rate." 8

The discharge of chronic schizophrenia patients from state men¬

tal hospitals —and thus the beginning of deinstitutionalization —got

under way in 1965 with the enactment of Medicare and Medicaid.

In 1955, there were 267,000 schizophrenia patients in state and

county mental hospitals, and eight years later, this number had

barely budged. There were still 253,000 schizophrenics residing in

the hospitals. 9 But then the economics of caring for the mentally ill

changed. The 1965 Medicare and Medicaid legislation provided

federal subsidies for nursing home care but no such subsidy for care

in state mental hospitals, and so the states, seeking to save money,

naturally began shipping their chronic patients to nursing homes.

That was when the census in state mental hospitals began to notice¬

ably drop, rather than in 1955, when Thorazine was introduced.

Unfortunately, our societal belief that it was this medication that

ANATOMY OF AN EPIDEMIC

emptied the asylums, which is so central to the "psychopharma-

cology revolution" narrative, is belied by the hospital census data.

Through a Lens Darkly

In 1955, pharmaceutical companies were not required to prove to

the FDA that their new drugs were effective (that requirement was

added in 1962), and thus it fell to the NIMH to assess the merits of

Thorazine and the other new "wonder drugs" coming to market.

Much to its credit, the NIMH organized a conference in September

1956 to "consider carefully the entire psychotropic question," and

ultimately the conversation at the conference focused on a very

particular question: How could psychiatry adapt, for its own use,

a scientific tool that had recently proven its worth in infectious

medicine: the placebo-controlled, double-blind, randomized clinical

trial? 10

As many speakers noted, this tool wasn't particularly well suited

for assessing outcomes of a psychiatric drug. How could a study of

a neuroleptic possibly be "double-blind"? The psychiatrist would

quickly see who was on the drug and who was not, and any patient

given Thorazine would know he was on a medication as well. Then

there was the problem of diagnosis: How would a researcher know

if the patients randomized into a trial really had "schizophrenia”?

The diagnostic boundaries of mental disorders were forever chang¬

ing. Equally problematic, what defined a "good outcome"? Psychi¬

atrists and hospital staff might want to see drug-induced behavioral

changes that made the patient "more socially acceptable” but

weren't to the "ultimate benefit of the patient," said one conference

speaker." And how could outcomes be measured? In a study of a

drug for a known disease, mortality rates or laboratory results

could serve as objective measures of whether a treatment worked.

For instance, to test whether a drug for tuberculosis was effective,

an X-ray of the lung could show whether the bacillus that caused

the disease was gone. What would be the measurable endpoint in a

A PARADOX REVEALED

trial of a drug for schizophrenia? The problem, said NIMH

physician Edward Evarts at the conference, was that "the goals of

therapy in schizophrenia, short of getting the patient 'well,' have

not been clearly defined ." 12

All of these questions bedeviled psychiatry, and yet the NIMH, in

the wake of that conference, made plans to mount a trial of the

neuroleptics. The push of history was simply too great. This was the

scientific method now used in internal medicine to assess the merits

of a therapy, and Congress had created the NIMH with the thought

that it would transform psychiatry into a more modern, scientific

discipline. Psychiatry's adoption of this tool would prove that it was

moving toward that goal. The NIMH established a Psychopharma¬

cology Service Center to head up this effort, and Jonathan Cole, a

psychiatrist from the National Research Council, was named its

director.

Over the next couple of years, Cole and the rest of psychiatry set¬

tled on a trial design for testing psychotropic drugs. Psychiatrists

and nurses would use "rating scales" to measure numerically the

characteristic symptoms of the disease that was to be studied. Did a

drug for schizophrenia reduce the patient's "anxiety"? His or her

"grandiosity”? "Hostility”? "Suspiciousness"? "Unusual thought

content"? "Uncooperativeness"? The severity of all of those symp¬

toms would be measured on a numerical scale and a total

"symptom” score tabulated, and a drug would be deemed effective

if it reduced the total score significantly more than a placebo did

within a six-week period.

At least in theory, psychiatry now had a way to conduct trials of

psychiatric drugs that would produce an "objective” result. Yet the

adoption of this assessment put psychiatry on a very particular

path: The field would now see short-term reduction of symptoms as

evidence of a drug's efficacy. Much as a physician in internal medi¬

cine would prescribe an antibiotic for a bacterial infection, a psychi¬

atrist would prescribe a pill that knocked down a "target symptom”

of a "discrete disease.” The six-week "clinical trial” would prove

that this was the right thing to do. However, this tool wouldn't pro¬

vide any insight into how patients were faring over the long term.

ANATOMY OF AN EPIDEMIC

Were they able to work? Were they enjoying life? Did they have

friends? Were they getting married? None of those questions would

be answered.

This was the moment that magic-bullet medicine shaped psychia¬

try's future. The use of the clinical trial would cause psychiatrists to

see their therapies through a very particular prism, and even at the

1956 conference, New York State Psychiatric Institute researcher

Joseph Zubin warned that when it came to evaluating a therapy for

a psychiatric disorder, a six-week study induced a kind of scientific

myopia. "It would be foolhardy to claim a definite advantage for a

specified therapy without a two- to five-year follow-up,” he said.

"A two-year follow-up would seem to be the very minimum for the

long-term effects." 13

The Case for Neuroleptics

The Psychopharmacology Service Center launched its nine-hospital

trial of neuroleptics in 1961, and this is the study that marks the be¬

ginning of the scientific record that serves today as the "evidence

base" for these drugs. In the six-week trial, 2 70 patients were given

Thorazine or another neuroleptic (which were also known as "phe-

nothiazines,”) while the remaining 74 were put on a placebo. The

neuroleptics did help reduce some target symptoms —unrealistic

thinking, anxiety, suspiciousness, auditory hallucinations, etc. —bet¬

ter than the placebo, and thus, according to the rating's scales cu¬

mulative score, they were effective. Furthermore, the psychiatrists in

the study judged 75 percent of the drug-treated patients to be

"much improved” or "very much .improved," versus 23 percent of

the placebo patients.

After that, hundreds of smaller trials produced similar results, and

thus the evidence that these drugs reduce symptoms over the short

term better than placebo is fairly robust.* In 1977, Ross Baldessarini

* In 2007, the Cochrane Collaboration, an international group of scientists

that doesn't take funding from pharmaceutical companies, raised questions

A PARADOX REVEALED

at Harvard Medical School reviewed 149 such trials and found that

the antipsychotic drug proved superior to a placebo in 83 percent of

them. 14 The "Brief Psychiatric Rating Scale” (BPRS) was regularly

employed in such trials, and the American Psychiatric Association

eventually decided that a 20 percent reduction in total BPRS score

represented a clinically significant response to a drug. 15 Based on this

measurement, an estimated 70 percent of all schizophrenia patients

suffering from an acute episode of psychosis "respond,” over a six-

week period, to an antipsychotic medication.

Once the NIMH investigators determined that the antipsychotics

were efficacious over the short term, they naturally wanted to know

how long schizophrenia patients should stay on the medication. To

investigate this question, they ran studies that, for the most part, had

this design: Patients who were good responders to the medication

were either maintained on the drug or abruptly withdrawn from it.

In 1995, Patricia Gilbert at the University of California at San Diego

reviewed sixty-six relapse studies, involving 4,365 patients, and she

found that 53 percent of the drug-withdrawn patients relapsed

within ten months versus 16 percent of those maintained on the

medications. "The efficacy of these medications in reducing the risk

of psychotic relapse has been well documented," she concluded.* 16

This is the scientific evidence that supports the use of anti¬

psychotic medications for schizophrenia, both in the hospital and

long-term. As John Geddes, a prominent British researcher, wrote in

about this short-term efficacy record. They conducted a meta-analysis of all

chlorpromazine-versus-placebo studies in the scientific literature, and after

identifying fifty of decent quality, they concluded that the advantage of drug

over placebo was smaller than commonly thought. They calculated that seven

patients had to be treated with chlorpromazine to produce a net gain of one

"global improvement," and that "even this finding may be an overestimate of

the positive and an understimate of the negative effects of giving chlorpro¬

mazine." The Cochrane investigators, somewhat startled by their results,

wrote that "reliable evidence about [chlorpromazine's] short-term efficacy is

surprisingly weak."

* There is an evident flaw with Gilbert's meta-analysis. She didn't determine

whether the speed with which drugs were withdrawn affected the relapse rate.

ANATOMY OF AN EPIDEMIC

a 2002 article in the New England Journal of Medicine, "Anti¬

psychotic drugs are effective in treating acute psychotic symptoms

and preventing relapse.” 17 Still, as many investigators have noted,

there is a hole in this evidence base, and it's the very hole that Zubin

predicted would arise. "Little can be said about the efficacy and ef¬

fectiveness of conventional antipsychotics on nonclinical outcomes,"

confessed Lisa Dixon and other psychiatrists at the University of

Maryland School of Medicine in 1995. "Well-designed long-term

studies are virtually nonexistent, so the longitudinal impact of treat¬

ment with conventional antipsychotics is unclear." 18

This doubt prompted an extraordinary 2002 editorial in Euro¬

pean Psychiatry, penned by Emmanuel Stip, a professor of psychia¬

try at the Universite de Montreal. "After fifty years of neuroleptics,

are we able to answer the following simple question: Are neuro¬

leptics effective in treating schizophrenia?" There was, he said, "no

compelling evidence on the matter, when 'long-term' is consid¬

ered." 19

A Conundrum Appears

Although Dixon's and Stip's comments suggest that there is no long¬

term data to be reviewed, it is in fact possible to piece together a

story of how antipsychotics alter the course of schizophrenia, and

this story begins, quite appropriately, with the NIMH's follow-up

study of the 344 patients in its initial nine-hospital trial. In some

ways, the patients —regardless of what treatment they had received

in the hospital —were not faring so badly. At the end of one year,

After her study appeared, Adele Viguera at Harvard Medical School reanalyzed

the same sixty-six studies and determined that when the drugs were gradually

withdrawn, the relapse rate was only one-third as high as in the abrupt-

withdrawal studies. The abrupt-withdrawal design in the majority of the re¬

lapse studies dramatically increased the risk that the schizophrenia patients

would become sick again. Indeed, the relapse rate for gradually withdrawn pa¬

tients was similar to what it was for the drug-maintained patients.

A PARADOX REVEALED

254 were living in the community, and 58 percent of those who —

according to their age and gender —could be expected to work were

in fact employed. Two-thirds of the "housewives" were functioning

OK in that domestic role. Although the researchers didn't report on

the medication use of patients during the one-year follow-up, they

were startled to discover that "patients who received placebo treat¬

ment [in the six-week trial] were less likely to be rehospitalized than

those who received any of the three active phenothiazines." 20

Here, at this very first moment in the scientific literature, there

is the hint of a paradox: While the drugs were effective over the short

term, perhaps they made people more vulnerable to psychosis over

the long term, and thus the higher rehospitalization rates for drug-

treated patients at the end of one year. Soon, NIMH investigators

were back with another surprising result. In two drug withdrawal

trials, both of which included patients who weren't on any drug at

the start of the study, relapse rates rose in correlation with drug

dosage. Only 7 percent of those who had been on a placebo at the

start of the study replapsed, compared to 65 percent of those taking

more than five hundred milligrams of chlorpromazine before the

drug was withdrawn. "Relapse was found to be significantly related

to the dose of the tranquilizing medication the patient was receiving

before he was put on placebo —the higher the dose, the greater the

probability of relapse,” the researchers wrote. 21

Something was amiss, and clinical observations deepened the sus¬

picion. Schizophrenia patients discharged on medications were re¬

turning to psychiatric emergency rooms in such droves that hospital

staff dubbed it the "revolving door syndrome.” Even when patients

reliably took their medications, relapse was common, and re¬

searchers observed that "relapse is greater in severity during drug

administration than when no drugs are given." 22 At the same time,

if patients relapsed after quitting the medications, Cole noted, their

psychotic symptoms tended to "persist and intensify," and, at least

for a time, they suffered from a host of new symptoms as well: nau¬

sea, vomiting, diarrhea, agitation, insomnia, headaches, and weird

motor tics. 23 Initial exposure to a neuroleptic seemed to be setting

patients up for a future of severe psychotic episodes, and that was

true regardless of whether they stayed on the medications.

loo

ANATOMY OF AN EPIDEMIC

These poor results prompted two psychiatrists at Boston Psycho¬

pathic Hospital, J. Sanbourne Bockoven and Harry Solomon, to

revisit the past. They had been at the hospital for decades, and in

the period after World War II ended, when they treated psychotic

patients with a progressive form of psychological care, they had

seen the majority regularly improve. That led them to believe that

"the majority of mental illnesses, especially the most severe, are

largely self-limiting in nature if the patient is not subjected to a

demeaning experience or loss of rights and liberties." The anti-

psychotics, they reasoned, should speed up this natural healing

process. But were the drugs improving long-term outcomes? In a

retrospective study, they found that 45 percent of the patients

treated in 1947 at their hospital hadn't relapsed in the next five

years and that 76 percent were successfully living in the community

at the end of that follow-up period. In contrast, only 31 percent of

the patients treated at the hospital in 1967 with neuroleptics

remained relapse-free for five years, and as a group they were much

more "socially dependent" —on welfare and needing other forms of

support. "Rather unexpectedly, these data suggest that psy¬

chotropic drugs may not be indispensable," Bockoven and Solomon

wrote. "Their extended use in aftercare may prolong the social

dependency of many discharged patients." 24

With debate over the merits of neuroleptics rising, the NIMH

funded three studies during the 1970s that reexamined whether

schizophrenia patients —and in particular those suffering a first

episode of schizophrenia —could be successfully treated without

medications. In the first study, which was conducted by William

Carpenter and Thomas McGlashan at the NIMH's clinical research

facility in Bethesda, Maryland, those treated without drugs were

discharged sooner than the drug-treated patients, and only 35 per¬

cent of the nonmedicated group relapsed within a year after dis¬

charge, compared to 45 percent of the medicated group. The

off-drug patients also suffered less from depression, blunted emo¬

tions, and retarded movements. Indeed, they told Carpenter and

McGlashan that they had found it "gratifying and informative” to

have gone through their psychotic episodes without having their

feelings numbed by the drugs. Medicated patients didn't have that

A PARADOX REVEALED

IOI

same learning experience, and as a result, Carpenter and Mc-

Glashan concluded, over the long term they "are less able to cope

with subsequent life stresses." 25

A year later, Maurice Rappaport at the University of California

in San Francisco announced results that told the same story, only

more strongly so. He had randomized eighty young newly diag¬

nosed male schizophrenics admitted to Agnews State Hospital into

drug and non-drug groups, and although symptoms abated more

quickly in those treated with antipsychotics, both groups, on aver¬

age, stayed only six weeks in the hospital. Rappaport followed the

patients for three years, and it was those who weren't treated with

antipsychotics in the hospital and who stayed off the drugs after

discharge that had —by far —the best outcomes. Only two of the

twenty-four patients in this never-exposed-to-antipsychotics group

relapsed during the three-year follow-up. Meanwhile, the patients

that arguably fared the worst were those on drugs throughout the

study. The very standard of care that, according to psychiatry's "ev¬

idence base,” was supposed to produce the best outcomes had

instead produced the worst.

"Our findings suggest that antipsychotic medication is not the

treatment of choice, at least for certain patients, if one is interested

in long-term clinical improvement,” Rappaport wrote. "Many

unmedicated-while-in-hospital patients showed greater long-term

Rappaport's Study: Three-Year Schizophrenia Outcomes

Medication Use

(In hospital/

after discharge)

Number of Patients

Severity Illness Scale

(1 = best outcome;

7 = worst outcome)

Rehospitalization

Placebo/off

1.70

Antipsychotic/off

1 7

2.79

4 7%

Placebo/on

1 7

3.54

5 3 %

Antipsychotic/on

3.51

7 3 %

In this study, patients were grouped according to both their in-hospital care (placebo or drug)

and whether they used antipsychotics after they were discharged. Thus, 24 ofthe 41 patients

treated with placebo in the hospital remained offthe drugs during the follow-up period.This

never-exposed group had the best outcomes by far. Rappaport, M."Are there schizophrenics for

whom drugs may be unnecessary or contraindicated." International Pharmacopsychiatry 13

(1 978): 1 00-1 1._

102

ANATOMY OF AN EPIDEMIC

improvement, less pathology at follow-up, fewer rehospitalizations,

and better overall functioning in the community than patients who

were given chlorpromazine while in the hospital." 26

The third study was led by Loren Mosher, head of schizophrenia

studies at the NIMH. Although he may have been the nation's top

schizophrenia doctor at the time, his vision of the illness was at

odds with many of his peers, who had come to think that schizo¬

phrenics suffered from a "broken brain." He believed that psy¬

chosis could arise in response to emotional and inner trauma and, in

its own way, could be a coping mechanism. As such, he believed

there was the possibility that people could grapple with their hallu¬

cinations and delusions, struggle through a schizophrenic break,

and regain their sanity. And if that was so, he reasoned that if he

provided newly psychotic patients with a safe house, one staffed by

people who had an evident empathy for others and who wouldn't

be frightened by strange behavior, many would get well, even

though they weren't treated with antipsychotics. "I thought that

sincere human involvement and understanding were critical to heal¬

ing interactions," he said. "The idea was to treat people as people,

as human beings, with dignity and respect.”

The twelve-room Victorian house he opened in Santa Clara,

California, in 1971 could shelter six patients at a time. He called it

Soteria House, and eventually he started a second home as well,

Emanon. All told, the Soteria Project ran for twelve years, with

eighty-two patients treated at the two homes. As early as 1974,

Mosher began reporting that his Soteria patients were faring better

than a matched cohort of patients being treated conventionally

with drugs in a hospital, and in 1979, he announced his two-year

results. At the end of six weeks, psychotic symptoms had abated as

much in his Soteria patients as in the hospitalized patients, and at

the end of two years, the Soteria patients had "lower psycho¬

pathology scores, fewer [hospital] readmissions, and better global

adjustment." 22 Later, he and John Bola, an assistant professor at the

University of Southern California, reported on their medication use:

Forty-two percent of the Soteria patients had never been exposed

to drugs, 39 percent had used them on a temporary basis, and only

19 percent had needed them throughout the two-year follow-up.

A PARADOX REVEALED

103

"Contrary to popular views, minimal use of antipsychotic med¬

ications combined with specially designed psychosocial intervention

for patients newly identified with schizophrenia spectrum disorder

is not harmful but appears to be advantageous,” Mosher and Bola

wrote. "We think that the balance of risks and benefits associated

with the common practice of medicating nearly all early episodes of

psychosis should be re-examined." 28

Three NIMH-funded studies, and all pointed to the same conclu¬

sion.* Perhaps 50 percent of newly diagnosed schizophrenia pa¬

tients, if treated without antipsychotics, would recover and stay

well through lengthy follow-up periods. Only a minority of patients

seemed to need to take the drugs continuously. The "revolving

door" syndrome that had become so familiar was due in large part

to the drugs, even though, in clinical trials, the drugs had proven to

be effective in knocking down psychotic symptoms. Carpenter and

McGlashan neatly summarized the scientific conundrum that psy¬

chiatry now faced:

There is no question that, once patients are placed on medica¬

tion, they are less vulnerable to relapse if maintained on

neuroleptics. But what if these patients had never been treated

with drugs to begin with? . . . We raise the possibility that

* In the early 1960s, Philip May conducted a study that compared five forms of

in-hospital treatment: drug, electroconvulsive therapy (ECT), psychotherapy,

psychotherapy plus drug, and milieu therapy (a supportive environment). Over

the short term, the drug-treated patients did much better. As a result, the study

came to be cited as proof that schizophrenia patients could not be treated with¬

out drugs. However, the two-year results told a more nuanced story. Fifty-nine

percent of patients initially treated with milieu therapy but no drugs were suc¬

cessfully discharged in the initial study period, and this group "functioned over

the follow-up at least as well, if not better, than the successes from the other

treatments." Thus, the May study, which is usually cited as proving that all

psychotic patients should be medicated, in fact suggested that a majority of

first-episode patients would fare best over the long term if initially treated with

milieu therapy rather than drugs. Source: P. May, "Schizophrenia: a follow-up

study of the results of five forms of treatment," Archives of General Psychiatry

38 (1981): 776-84.

104

ANATOMY OF AN EPIDEMIC

antipsychotic medication may make some schizophrenic pa¬

tients more vulnerable to future relapse than would be the

case in the natural course of the illness. 29

And if that was so, these drugs were increasing the likelihood

that a person who suffered a psychotic break would become chron¬

ically ill.

A Cure Worse Than the Disease?

All drugs have a risk-benefit profile, and the usual thought within

medicine is that a drug should provide a benefit that outweighs the

risks. A drug that curbs psychotic symptoms clearly provides a

marked benefit, and that was why antipsychotics could be viewed as

helpful even though the list of negatives with these drugs was a long

one. Thorazine and other first-generation neuroleptics caused

Parkinsonian symptoms and extraordinarily painful muscle spasms.

Patients regularly complained that the drugs turned them into emo¬

tional "zombies.” In 1972, researchers concluded that neuroleptics

"impaired learning." 30 Others reported that even if medicated pa¬

tients stayed out of the hospital, they seemed totally unmotivated

and socially disengaged. Many lived in "virtual solitude” in group

homes, spending most of the time "staring vacantly at television,"

wrote one investigator. 31 None of this told of medicated schizophre¬

nia patients faring well, and here was the quandary that psychiatry

now faced: If the drugs increased relapse rates over the long term,

then where was the benefit? This question was made all the more

pressing by the fact that many patients maintained on the drugs

were developing tardive dyskinesia (TD), a gross motor dysfunction

that remained even after the drugs were withdrawn, evidence of per¬

manent brain damage.

All of this required psychiatry to recalculate the risks and benefits

of antipsychotics, and in 1977 Jonathan Cole did so in an article

provocatively titled "Is the Cure Worse Than the Disease?” He

reviewed all of the long-term harm the drugs could cause and

A PARADOX REVEALED

• 105

observed that studies had shown that at least 50 percent of all schiz¬

ophrenia patients could fare well without the drugs. There was only

one moral thing for psychiatry to do: "Every schizophrenic outpa¬

tient maintained on antipsychotic medication should have the bene¬

fit of an adequate trial without drugs.” This, he explained, would

save many "from the dangers of tardive dyskinesia as well as the

financial and social burdens of prolonged drug therapy." 32

The evidence base for maintaining schizophrenia patients on

antipsychotics had collapsed. "Are the antipsychotics to be with¬

drawn?” asked Pierre Deniker, the French psychiatrist who, in the

early 1950s, had first promoted their use. 33

Supersensitivity Psychosis

In the late 1970s, two physicians at McGill University, Guy

Chouinard and Barry Jones, stepped forward with a biological ex¬

planation for why the drugs made schizophrenia patients more

biologically vulnerable to psychosis. Their understanding arose, in

large part, from the investigations into the dopamine hypothesis of

schizophrenia, which had detailed how the drugs perturbed this

neurotransmitter system.

Thorazine and other standard antipsychotics block 70 to 90 per¬

cent of all D, receptors in the brain. In an effort to compensate for

this blockade, the postsynaptic neurons increase the density of their

D= receptors by 30 percent or more. The brain is now "supersensi¬

tive" to dopamine, Chouinard and Jones explained, and this neuro¬

transmitter is thought to be a mediator of psychosis. "Neuroleptics

can produce a dopamine supersensitivity that leads to both dyski-

netic and psychotic symptoms," they wrote. "An implication is that

the tendency toward psychotic relapse in a patient who has devel¬

oped such a supersensitivity is determined by more than just the

normal course of the illness." 31

A simple metaphor can help us better understand this drug-induced

biological vulnerability to psychosis and why it flares up when the

drug is withdrawn. Neuroleptics put a brake on dopamine trans-

io6

ANATOMY OF AN EPIDEMIC

mission, and in response the brain puts down the dopamine acceler¬

ator (the extra Dj receptors). If the drug is abruptly withdrawn, the

brake on dopamine is suddenly released while the accelerator is still

pressed to the floor. The system is now wildly out of balance, and

just as a car might careen out of control, so too the dopaminergic

pathways in the brain. The dopaminergic neurons in the basal

ganglia may fire so rapidly that the patient withdrawing from the

drugs suffers weird tics, agitation, and other motor abnormalities.

The same out-of-control firing is happening with the dopaminergic

pathway to the limbic region, and that may lead to "psychotic

relapse or deterioration,” Chouinard and Jones wrote. 35

This was an extraordinary piece of scientific detective work by

the two Canadian investigators. They had —at least in theory —

identified the reason that relapse rates were so high in the medication-

withdrawal trials, which psychiatry had mistakenly interpreted as

proving that the drugs prevented relapse. The severe relapse suffered

by many patients withdrawn from antipsychotics was not necessar¬

ily the result of the "disease" returning, but rather was drug-related.

Chouinard and Jones's work also revealed that both psychiatrists

and their patients would regularly suffer from a clinical delusion:

They would see the return of psychotic symptoms upon drug with¬

drawal as proof that the antipsychotic was necessary and that it

"worked.” The relapsed patient would then go back on the drug and

often the psychosis would abate, which would be further proof that

it worked. Both doctor and patient would experience this to be

"true,” and yet, in fact, the reason that the psychosis abated with the

return of the drug was that the brake on dopamine transmission was

being reapplied, which countered the stuck dopamine accelerator. As

Chouinard and Jones explained: "The need for continued neurolep¬

tic treatment may itself be drug-induced.”

In short, initial exposure to neuroleptics put patients onto a path

where they would likely need the drugs for life. Yet—and this was

the second haunting aspect to this story of medicine —staying on the

drugs regularly led to a bad end. Over time, Chouinard and Jones

noted, the dopaminergic pathways tended to become permanently

dysfunctional. They became irreversibly stuck in a hyperactive state,

A PARADOX REVEALED

• 107

and soon the patient's tongue was slipping rhythmically in and out

of his mouth (tardive dyskinesia) and psychotic symptoms were

worsening (tardive psychosis). Doctors would then need to pre¬

scribe higher doses of antipsychotics to tamp down those tardive

symptoms. "The most efficacious treatment is the causative agent it¬

self, the neuroleptic,” Chouinard and Jones said.

Over the next few years, Chouinard and Jones continued to flesh

out and test their hypothesis. In 1982, they reported that 30 percent

of 216 schizophrenia outpatients they studied showed signs of tar¬

dive psychosis. 36 They also observed that it tended to afflict those

patients who, at initial diagnosis, had a "good prognosis," and thus

would have had a chance to fare well over the long term if they had

never been exposed to neuroleptics. These were the "placebo re¬

sponders" who had fared best in the studies conducted by Rappa-

port and Mosher, and now Chouinard and Jones were reporting

that they were becoming chronically psychotic after years of taking

antipsychotics. Finally, Chouinard quantified the risk, reporting that

tardive psychosis seemed to develop at a slightly slower rate than

tardive dyskinesia. It afflicted 3 percent of patients a year, with the

result that after fifteen years on the drugs, perhaps 45 percent suf¬

fered from it. When tardive psychosis sets in, Chouinard added,

"the illness appears worse” than ever before. "New schizophrenic

or original symptoms of greater severity will appear." 37

Animal studies confirmed this picture too. Philip Seeman re¬

ported that antipsychotics caused an increase in Dz receptors in rats,

and while the density of these receptors could revert to normal if the

drug was withdrawn (he reported that for every month of exposure,

it took two months for renormalization to occur), at some point the

increase in receptors became irreversible. 38

In 1984, Swedish physician Lars Martensson, in a presentation at

the World Federation of Mental Health Conference in Copenhagen,

summed up the devastating bottom line. "The use of neuroleptics is

a trap," he said. "It is like having a psychosis-inducing agent built

into the brain." 39

io8

ANATOMY OF AN EPIDEMIC

A Crazy Idea ... Or Not?

This was the view of neuroleptics that came together in the early

1980s, and it was a story of science at its best. Psychiatrists saw that

the drugs "worked.” They saw that antipsychotics knocked down

psychotic symptoms, and they observed that patients who stopped

taking their medications regularly became psychotic again. Scien¬

tific tests reinforced their clinical perceptions. Six-week trials proved

the drugs were effective. Relapse studies proved that patients should

be maintained on the drugs. Yet once researchers came to under¬

stand how the drugs acted on the brain, and once they began inves¬

tigating why patients were developing tardive dyskinesia and why

they were becoming so chronically ill, then this counterintuitive pic¬

ture of the drugs —that they were increasing the likelihood that pa¬

tients would become chronically ill —emerged. It was Chouinard

and Jones who explicitly connected all the dots, and for a time, their

work did stir up a hornet's nest within psychiatry. One physician, at

a meeting where the two McGill University doctors spoke, asked in

astonishment: "I put my patients on neuroleptics because they're

psychotic. Now you're saying that the same drug that controls their

schizophrenia also causes a psychosis?" 40

But what was psychiatry supposed to do with this information? It

clearly imperiled the field's very foundation. Could it really now

confess to the public, or even admit to itself, that the very class of

drugs said to have "revolutionized” the care of the mentally ill was

in fact making patients chronically ill? That antipsychotics made

patients —at least in the aggregate —more psychotic over time? Psy¬

chiatry desperately needed this discussion to go away. Soon the arti¬

cles by Chouinard and Jones on "supersensitivity psychosis” were

filed away in the "interesting hypothesis" category, and everyone in

the field breathed a sigh of relief when Solomon Snyder, who knew

as much about dopamine receptors as any scientist in the world, as¬

sured everyone in his 1986 book Drugs and the Brain that it had all

turned out to be a false alarm. "If dopamine receptor sensitivity is

greater in patients with tardive dyskinesia, one might wonder

whether they would also suffer a corresponding increase in schizo-

A PARADOX REVEALED

109

phrenia symptoms. Interestingly, though researchers have looked

carefully for any possible exacerbation of schizophrenic symptoms

in patients who begin to develop tardive dyskinesia, none has ever

been found." 41

That moment of crisis within psychiatry, when it briefly worried

about supersensitivity psychosis, occurred nearly thirty years ago,

and today the notion that antipsychotics increase the likelihood that

a person diagnosed with schizophrenia will become chronically ill

seems, on the face of it, absurd. Ask psychiatrists at top medical

schools, staff at a mental hospital, NIMH officials, leaders of the

National Alliance for the Mentally 111, science writers at major

newspapers, or the ordinary person in the street, and everyone will

attest that antipsychotics are essential for treating schizophrenia,

the very cornerstone of care, and that anyone who touts a different

idea is, well, a bit loony. Still, we started down this path of research,

I've invited readers into this loony bin, and so now we need to move

up one floor in the Countway Library. The volumes in the basement

end in 1986, and now we need to comb the scientific literature since

that date, and see what story it has to tell. Was it all a false

alarm ... or not?

The most efficient way to answer that question is to summarize,

one by one, the relevant studies and avenues of research.

The Vermont longitudinal study

In the late 1950s and early 1960s, Vermont State Hospital dis¬

charged 269 chronic schizophrenics, most of whom were middle-

aged, into the community. Twenty years later, Courtenay Harding

interviewed 168 patients from this cohort (those who were still

alive), and found that 34 percent were recovered, which meant they

were "asymptomatic and living independently, had close relation¬

ships, were employed or otherwise productive citizens, were able to

care for themselves, and led full lives in general." 42 This was a star¬

tling good long-term outcome for patients who had been seen as

hopeless in the 1950s, and those who had recovered, Harding told

the APA Monitor, had one thing in common: They all "had long

since stopped taking medications." 43 She concluded that it was a

ANATOMY OF AN EPIDEMIC

"myth" that schizophrenia patients "must be on medication all

their lives," and that, in fact, "it may be a small percentage who

need medication indefinitely." 44

The World Health Organization cross-cultural studies

In 1969, the World Health Organization launched an effort to track

schizophrenia outcomes in nine countries. At the end of five years,

the patients in the three "developing” countries —India, Nigeria,

and Colombia —had a "considerably better course and outcome”

than patients in the United States and five other "developed coun¬

tries.” They were much more likely to be asymptomatic during the

follow-up period, and even more important, they enjoyed "an ex¬

ceptionally good social outcome.”

These findings stung the psychiatric community in the United

States and Europe, which protested that there must have been a de¬

sign flaw in the study. Perhaps the patients in India, Nigeria, and

Colombia had not really been schizophrenic. In response, WHO

launched a ten-country study in 1978, and this time they primarily

enrolled patients suffering from a first episode of schizophrenia, all

of whom were diagnosed by Western criteria. Once again, the re¬

sults were much the same. At the end of two years, nearly two-

thirds of the patients in the "developing countries" had had good

outcomes, and slightly more than one-third had become chronically

ill. In the rich countries, only 37 percent of the patients had good

outcomes, and 59 percent became chronically ill. "The findings of a

better outcome of patients in developing countries was confirmed,”

the WHO scientists wrote. "Being in a developed country was a

strong predictor of not attaining a complete remission." 45

Although the WHO investigators didn't identify a reason for the

stark disparity in outcomes, they had tracked antipsychotic usage in

the second study, having hypothesized that perhaps patients in the

poor countries fared better because they more reliably took their

medication. However, they found the opposite to be true. Only 16

percent of the patients in the poor countries were regularly main¬

tained on antipsychotics, versus 61 percent of the patients in the

rich countries. Moreover, in Agra, India, where patients arguably

A PARADOX REVEALED • III

fared the best, only 3 percent of the patients were kept on an

antipsychotic. Medication usage was highest in Moscow, and that

city had the highest percentage of patients who were constantly ill. 46

In this cross-cultural study, the best outcomes were clearly associ¬

ated with low medication use. Later, in 1997, WHO researchers in¬

terviewed the patients from the first two studies once again (fifteen

to twenty-five years after the initial studies), and they found that

those in the poor countries continued to do much better. The "out¬

come differential” held up for "general clinical state, symptomatol¬

ogy, disability, and social functioning.” In the developing countries,

53 percent of the schizophrenia patients were simply "never psy¬

chotic” anymore, and 73 percent were employed. 47 Although the

WHO investigators didn't report on medication usage in their

follow-up study, the bottom line is clear: In countries where patients

hadn't been regularly maintained on antipsychotics earlier in their

illness, the majority had recovered and were doing well fifteen years

later.

Tardive dyskinesia and global decline

Tardive dyskinesia and tardive psychosis occur because the

dopaminergic pathways to the basal ganglia and limbic system be¬

come dysfunctional. But there are three dopaminergic pathways,

and so it stands to reason that the third one, which transmits mes¬

sages to the frontal lobes, also becomes dysfunctional over time. If

so, researchers could expect to find a global decline in brain func¬

tion in patients diagnosed with tardive dyskinesia, and from 1979

to 2000, more than two dozen studies found that to be the case.

"The relationship appears to be linear,” reported Medical College

of Virginia psychiatrist James Wade in 1987. "Individuals with se¬

vere forms of the disorder are most impaired cognitively." 48 Re¬

searchers determined that tardive dyskinesia was associated with a

worsening of the negative symptoms of schizophrenia (emotional

disengagement); psychosocial impairment; and a decline in memory,

visual retention, and the capacity to learn. People with TD lose their

"road map of consciousness," concluded one investigator. 49 Investi¬

gators have dubbed this long-term cognitive deterioration tardive

112

ANATOMY OF AN EPIDEMIC

dementia; in 1994, researchers found that three-fourths of med¬

icated schizophrenia patients seventy years and older suffer from a

brain pathology associated with Alzheimer's disease. 50

MRI studies

The invention of magnetic resonance imaging technology provided

researchers with the opportunity to measure volumes of brain struc¬

tures in people diagnosed with schizophrenia, and while they hoped

to identify abnormalities that might characterize the illness, they

ended up documenting instead the effect of antipsychotics on brain

volumes. In a series of studies from 1994 to 1998, investigators re¬

ported that the drugs caused basal ganglion structures and the thal¬

amus to swell, and the frontal lobes to shrink, with these changes in

volumes "dose related." 51 Then, in 1998, Raquel Gur at the Univer¬

sity of Pennsylvania Medical Center reported that the swelling of

the basal ganglia and thalamus was "associated with greater sever¬

ity of both negative and positive symptoms." 52

This last study provided a very clear picture of an iatrogenic

process. The antipsychotic causes a change in brain volumes, and as

this occurs, the patient becomes more psychotic (known as the

"positive symptoms" of schizophrenia) and more emotionally dis¬

engaged ("negative symptoms"). The MRI studies showed that

antipsychotics worsen the very symptoms they are supposed to

treat, and that this worsening begins to occur during the first three

years that patients are on the drugs.

Modeling psychosis

As part of their investigations of schizophrenia, researchers have

sought to develop biological "models" of psychosis, and one way

they have done that is to study the brain changes induced by various

drugs —amphetamines, angel dust, etc. —that can trigger delusions

and hallucinations. They also have developed ways to induce

psychotic-like behaviors in rats and other animals. Lesions to the

hippocampus can cause such disturbed behaviors; certain genes can

be "knocked out" to produce such symptoms. In 2005, Philip

A PARADOX REVEALED

113

Seeman reported that all of these psychotic triggers cause an in¬

crease in D 2 receptors in the brain that have a "HIGH affinity” for

dopamine, and by that, he meant that the receptors bound quite

easily with the neurotransmitter. These "results imply that there

may be many pathways to psychosis, including multiple gene muta¬

tions, drug abuse, or brain injury, all of which may converge via D,

HIGH to elicit psychotic symptoms," he wrote. 53

Seeman reasoned that this is why antipsychotics work: They

block D 2 receptors. But in his research, he also found that these

drugs, including the newer ones like Zyprexa and Risperdal, double

the density of "high affinity” Di receptors. They induce the same

abnormality that angel dust does, and thus this research confirms

what Lars Martensson observed in 1984: Taking a neuroleptic is

like having a "psychosis inducing agent built into the brain."

Nancy Andreasen’s longitudinal MRI study

In 1989, Nancy Andreasen, a psychiatry professor at the University

of Iowa who was editor in chief of the American Journal of Psychi¬

atry from 1993 to 2005, began a long-term study of more than five

hundred schizophrenia patients. In 2003, she reported that at the

time of initial diagnosis, the patients had slightly smaller frontal

lobes than normal, and that over the next three years, their frontal

lobes continued to shrink. Furthermore, this "progressive reduction

in frontal lobe white matter volume” was associated with a worsen¬

ing of negative symptoms and functional impairment, and thus An¬

dreasen concluded that this shrinkage is evidence that schizophrenia

is a "progressive neurodevelopmental disorder," one which antipsy¬

chotics unfortunately fail to arrest. "The medications currently used

cannot modify an injurious process occurring in the brain, which is

the underlying basis of symptoms." 54

Hers was a picture of antipsychotics as therapeutically ineffec¬

tive, rather than harmful, and two years later, she fleshed out this

picture. Her patients' cognitive abilities began to "worsen signifi¬

cantly” five years after initial diagnosis, a decline tied to the "pro¬

gressive brain volume reductions after illness onset." 55 In other

words, as her patients' frontal lobes shrank in size, their ability

114

ANATOMY OF AN EPIDEMIC

to think declined. But other researchers conducting MRI studies

had found that the shrinkage of the frontal lobes was drug-related,

and in a 2008 interview with the New York Titties, Andreasen con¬

ceded that the "more drugs you've been given, the more brain tissue

you lose.” The shrinkage of the frontal lobes may be part of a

disease process, which the drugs then exacerbate. "What exactly do

these drugs do?” Andreasen said. "They block basal ganglia activ¬

ity. The prefrontal cortex doesn't get the input it needs and is being

shut down by drugs. That reduces the psychotic symptoms. It also

causes the prefrontal cortex to slowly atrophy.” 56

Once again, Andreasen's investigations revealed an iatrogenic

process at work. The drugs block dopamine activity in the brain

and this leads to brain shrinkage, which in turn correlates with a

worsening of negative symptoms and cognitive impairment. This

was yet another disturbing finding, and it prompted Yale psychia¬

trist Thomas McGlashan, who three decades earlier had wondered

whether antipsychotics were making patients "more biologically

vulnerable to psychosis," to once again question this entire para¬

digm of care. He put his troubled thoughts into a scientific context:

In the short term, acute D 2 [receptor] blockade detaches

salience and the patient's investment in positive symptoms. In

the long term, chronic D 2 blockade dampens salience for all

events in everyday life, inducing a chemical anhedonia that is

sometimes labeled postpsychotic depression or neuroleptic

dysphoria. . . . Do we free patients from the asylum with D 2

blocking agents only to block incentive, engagement with the

world, and the joie de vivre of everyday life? Medication can

be lifesaving in a crisis, but it may render the patient more

psychosis-prone should it be stopped and more deficit-ridden

should it be maintained. 57

His comments appeared in a 2006 issue of the Schizophrenia Bul¬

letin, and at that moment it seemed like the late 1970s all over

again. The "cure,” it seemed, had once again been proven to be

"worse than the disease."

A PARADOX REVEALED

11$

The Clinician's Illusion

I attended the 2008 meeting of the American Psychiatric Associa¬

tion for a number of reasons, but the person I most wanted to hear

speak was Martin Harrow, who is a psychologist at the University

of Illinois College of Medicine. From 1975 to 1983, he enrolled

sixty-four young schizophrenics in a long-term study funded by the

NIMH, recruiting the patients from two Chicago hospitals. One

was private and the other public, as this ensured that the group

would be economically diverse. Ever since then, he has been period¬

ically assessing how well they are doing. Are they symptomatic? In

recovery? Employed? Do they take antipsychotic medications? His

results provide an up-to-date look at how schizophrenia patients in

the United States are faring, and thus his study can bring our in¬

vestigation of the scientific literature to a fitting climax. If the con¬

ventional wisdom is to be believed, then those who stayed on

antipsychotics should have had better outcomes. If the scientific lit¬

erature we have just reviewed is to be believed, then it should be the

reverse.

Here is Harrow's data. In 2007, he published a report on the pa¬

tients' fifteen-year outcomes in the Journal of Nervous and Mental

Disease, and he further updated that review in his presentation at

the APA's 2008 meeting. 58 At the end of two years, the group not on

antipsychotics were doing slightly better on a "global assessment

scale” than the group on the drugs. Then, over the next thirty

months, the collective fates of the two groups began to dramatically

diverge. The off-med group began to improve significantly, and by

the end of 4.5 years, 39 percent were "in recovery" and more than

60 percent were working. In contrast, outcomes for the medication

group worsened during this thirty-month period. As a group, their

global functioning declined slightly, and at the 4.5-year mark, only

6 percent were in recovery and few were working. That stark diver¬

gence in outcomes remained for the next ten years. At the fifteen-

year follow-up, 40 percent of those off drugs were in recovery, more

than half were working, and only 28 percent suffered from psy¬

chotic symptoms. In contrast, only 5 percent of those taking anti-

I 1 6

ANATOMY OF AN EPIDEMIC

Long-term Recovery Rates for Schizophrenia Patients

50%

2 4.5 7.5 10 15

Year Year Year Year Year

Follow-up Follow-up Follow-up Follow-up Follow-up

Source: Harrow, M. "Factors involved in outcome and recovery in schizophrenia patients not on

antipsychotic medications." The Journal of Nervous and Mental Disease, 1 95 (2007): 406-1 4.

psychotics were in recovery, and 64 percent were actively psychotic.

"I conclude that patients with schizophrenia not on antipsychotic

medication for a long period of time have significantly better global

functioning than those on antipsychotics," Harrow told the APA

audience.

Indeed, it wasn't just that there were more recoveries in the un¬

medicated group. There were also fewer terrible outcomes in this

group. There was a shift in the entire spectrum of outcomes. Ten of

the twenty-five patients who stopped taking antipsychotics recov¬

ered, eleven had so-so outcomes, and only four (16 percent) had a

"uniformly poor outcome.” In contrast, only two of the thirty-nine

patients who stayed on antipsychotics recovered, eighteen had so-so

outcomes, and nineteen (49 percent) fell into the "uniformly poor”

camp. Medicated patients had one-eighth the recovery rate of un¬

medicated patients, and a threefold higher rate of faring miserably

over the long term.

This is the outcomes picture revealed in an NIMH-funded study,

A PARADOX REVEALED

• 117

Spectrum ofOutcomes in Schizophrenia Patients

On Antipsychotics

Off Antipsychotics

The spectrum ofoutcomes for medicated versus unmedicated patients. Those on antipsychotics

had a much lower recovery rate, and were much more likely to have a "uniformly poor" outcome.

Source: Harrow, M. "Factors involved in outcome and recovery in schizophrenia patients not on

antipsychotic medications." The Journal of Nervous and Mental Disease, 1 95 (2007): 406-14.

the most up-to-date one we have today. It also provides us with in¬

sight into how long it takes for the better outcomes for nonmedi-

cated patients, as a group, to become apparent. Although this

difference began to show up at the end of two years, it wasn't until

the 4.5-year mark that it became evident that the nonmedicated

group, as a whole, was doing much better. Furthermore, through his

rigorous tracking of patients, Harrow discovered why psychiatrists

remain blind to this fact. Those who got off their antipsychotic

medications left the system, he said. They stopped going to day pro¬

grams, they stopped seeing therapists, they stopped telling people

they had ever been diagnosed with schizophrenia, and they disap¬

peared into society. A few of the nonmedicated people in Harrow's

study even got "high-level jobs” —one became a college professor

and another a lawyer —and several had "mid-level jobs.” Explained

Harrow: "We [clinicians] get our experience from seeing those who

leave us, and then come back because they relapse. We don't see the

ones who don't relapse. They don't come back. They are quite

happy.”

Afterward, I asked Dr. Harrow why he thought the nonmedi¬

cated patients did so much better. He did not attribute it to their

being off antipsychotics, but rather said it was because this group

"had a stronger internal sense of self,” and once they initially stabi¬

lized on the medications, this "better personhood” gave them the

118 •

ANATOMY OF AN EPIDEMIC

confidence to go off the drugs. "It's not that those who went off

medications did better, but rather it was those who did better [ini¬

tially] who then went off the medications.” When I pressed on with

a question about whether his findings supported a different inter¬

pretation, which was that the drugs worsened long-term outcomes,

he grew a bit testy. "That's a possibility, but I'm not advocating it,”

he said. "People recognize there may be side effects. . . . I'm not just

trying to avoid the question. I'm one of the few people in the field

without drug money."

I asked one last question. At the very least, shouldn't his findings

be worked into the paradigm of care used in our society to treat

those diagnosed with schizophrenia? "There is no question about

that," he replied. "Our data is overwhelming that not all schizo¬

phrenic patients need to be on antipsychotics all their lives."

Reviewing the Evidence

We have followed a trail of documents to a surprising end, and thus

I think we need to ask one final question: Does the evidence refuting

the common wisdom all hang together? In other words, does the

outcomes literature tell a coherent and consistent story? We need to

double-check to make sure we are not missing something, for it is

always discomforting to arrive at a conclusion so at odds with what

society "knows" to be true.

First, as researchers Lisa Dixon and Emmanuel Stip acknowl¬

edged, there is no good evidence that antipsychotics improve long¬

term schizophrenia outcomes. As such, we can be confident that we

haven't missed any such studies in our survey. Second, evidence that

the drugs might worsen long-term outcomes showed up in the very

first follow-up study conducted by the NIMH, and then it appears

again and again over the next fifty years. We can link the authors

of this research into a lengthy chain: Cole, Bockoven, Rappaport,

Carpenter, Mosher, Harding, the World Health Organization, and

Harrow. Third, once researchers came to understand how anti-

A PARADOX REVEALED

119

psychotics affected the brain, Chouinard and Jones stepped forward

with a biological explanation for why the drugs made patients more

vulnerable to psychosis over the long term. They were also able to

explain why the drug-induced brain changes made it so risky for

people to go off the medications, and thus they revealed why the

drug-withdrawal studies misled psychiatrists into believing that the

drugs prevented relapse. Fourth, evidence that long-term recovery

rates are higher for nonmedicated patients appears in studies and

investigations of many different types. It shows up in the random¬

ized studies conducted by Rappaport, Carpenter, and Mosher; in

the cross-cultural studies conducted by the World Health Organiza¬

tion; and in the naturalistic studies conducted by Harding and Har¬

row. Fifth, we see in the tardive dyskinesia studies evidence that

the drugs induce global brain dysfunction in a high percentage of

patients over the long term. Sixth, once a new tool for studying

brain structures came along (MRIs), investigators discovered that

antipsychotics cause morphological changes in the brain and that

these changes are associated with a worsening of both positive and

negative symptoms, and with cognitive impairment as well. Finally,

for the most part, the psychiatric researchers who conducted these

studies hoped and expected to find the reverse. They wanted to tell

a story of drugs that help schizophrenia patients fare well over the

long term —their bias was in that direction.

We are trying to solve a puzzle in this book —why have the num¬

ber of disabled mentally ill soared over the past fifty years —and I

think we now have our first puzzle piece in hand. We saw that in the

decade before the introduction of Thorazine, 65 percent or so of

first-episode schizophrenics would be discharged within twelve

months, and the majority of those discharged would not be rehospi¬

talized in follow-up periods of four and five years. This was what

we saw in Bockoven's study, too: Seventy-six percent of the psy¬

chotic patients treated with a progressive form of psychosocial care

in 1947 were living successfully in the community five years later.

But, as we saw in Harrow's study, only 5 percent of schizophrenia

patients who stayed on their drugs long-term ended up recovered.

That is a dramatic decline in recovery rates in the modern era, and

120

ANATOMY OF AN EPIDEMIC

older psychiatrists, who can still remember what it was like to work

with unmedicated patients, can personally attest to this difference in

outcomes.

"In the nonmedication era, my schizophrenic patients did far bet¬

ter than do those in the more modern era," said Maryland psychia¬

trist Ann Silver, in an interview. "They chose careers, pursued them,

and married. One patient, who had been called the sickest admitted

to the adolescent division [of her hospital], is raising three children

and works as a registered nurse. In the later [medicated] era, none

chose a career, although many held various jobs, and none married

or even had lasting relationships."

We can also see how this drug-induced chronicity has con¬

tributed to the rise in the number of disabled mentally ill. In 1955,

there were 267,000 people with schizophrenia in state and county

mental hospitals, or one in every 617 Americans. Today, there are

an estimated 2.4 million people receiving SSI or SSDI because they

are ill with schizophrenia (or some other psychotic disorder), a dis¬

ability rate of one in every 125 Americans. 59 Since the arrival of

Thorazine, the disability rate due to psychotic illness has increased

fourfold in our society.

Cathy, George, and Kate

In the second chapter, we met two people —Cathy Levin and George

Badillo —who had been diagnosed with schizoaffective disorder

(Cathy) or schizophrenia (George). We can now see how their

stories fit into the outcomes literature.

As I said, Cathy Levin is one of the best responders to atypical

antipsychotics that I've ever met. She could be Janssen's poster girl

for promoting Risperdal. Still, she remains on SSDI and she per¬

ceives the medications as a barrier to her working full-time. Now

let's go back to that moment when she had her first psychotic

episode at Earlham College. What might her life have been like if

she had not been immediately placed on neuroleptics, but instead

A PARADOX REVEALED

121

had been treated with some form of psychosocial care? Or if, at

some point early on, she had been encouraged to withdraw gradu¬

ally from the antipsychotic medication? Would she have cycled in

and out of hospitals for the next twelve years? Would she have

ended up on SSDI? Although we can't really answer those ques¬

tions, we can say that the drug treatment increased the likelihood

that she would suffer that long period of constant hospitalizations,

and decreased the likelihood that she would fully recover from her

initial crackup. As Cathy said: "The thing I remember, looking

back, is that I was not really that sick early on. I was really just con¬

fused.

Meanwhile, George Badillo's story illustrates how getting off

meds can be the key to recovery, at least for some people diagnosed

with schizophrenia. His journey out of the back wards of a state

hospital began when he started tonguing his antipsychotic medica¬

tion. He is healthy today, he has an evident zest for life, and he rev¬

els in being a good father to his son and having his daughter

Madelyne back in his life. He is an example of the many recovered

people who showed up in the long-term studies by Harding and

Harrow —former patients who have quit taking antipsychotics and

are doing well.

Here is a third story of a young woman I'll call Kate, as she did

not want her real name used. Diagnosed with schizophrenia at age

nineteen, she did well on antipsychotics. In Harrow’s study, she

would have been among the 5 percent on meds who recovered. But

she also knows what it is like to be off meds and doing well, and

from her perspective, the latter type of recovery is totally unlike the

first.

Before I met Kate in person, I knew from a phone conversation

the bare outlines of her story, of how she had spent ten years on

antipsychotics, and given that those drugs can take such a physical

toll, I was a bit startled by her appearance when she showed up at

my office. To be blunt, the words "drop dead gorgeous" popped

into my head. A dark-haired woman, she wore jeans, a roseate top,

and light makeup, and she introduced herself in a confident, warm

way. Soon, she was showing me a "before” picture taken three

122

ANATOMY OF AN EPIDEMIC

years earlier. "I was well over two-hundred pounds," she says. "I

was very slow, my face was droopy. I smoked a lot of cigarettes. . . .

It was very inhibiting to any sort of professional look."

Kate's story about her childhood is a familiar one. Her parents

divorced when she was eight, and she remembers herself as socially

awkward and horribly shy. "I only had social skills enough to inter¬

act with my family members," she says, and that awkwardness fol¬

lowed her to college. During her freshman year at the University of

Massachusetts at Dartmouth, she found it difficult to make friends,

and she felt so isolated that she cried constantly. Early in her sopho¬

more year she dropped out and went to live with her mother in

Boston, hoping to find a "purpose in life.” Instead, "my sense of re¬

ality started to disintegrate,” she recalls. "I started worrying about

God versus the devil, and I started becoming afraid of everything.

I'd say to my mom's friend, 'Is the food poisoned?' I was acting

quite bizarre, and I couldn't make sense of the conversations around

me. I would say these very odd things, and I would speak very

slowly, very deliberately, and weird.”

When she began talking about seeing wolves in her bedroom, her

mother put her in the hospital. Although she stabilized pretty well

on the antipsychotic medication, she hated how it made her feel,

and not long after she was discharged, she abruptly went off it,

which triggered a florid psychotic break. During her second hospi¬

talization, in February 1997, she was diagnosed with schizophrenia,

and this time she accepted the fact that she would have to take anti-

psychotics for life. Eventually, she found a two-drug combination

that worked well for her, and she began rebuilding a life. In 2001,

she graduated from UMass Boston, and a year later she married a

man she had met in a day treatment program. "We both had a psy¬

chiatric disability, and we both smoked heavily," she says. "We both

saw therapists daily. This is what we had in common."

Kate took a job in a group home for the mentally handicapped,

and although at times she had trouble staying awake, a side effect of

her medications, she earned enough to get off SSDI. For a person

with schizophrenia, she was doing extremely well. Yet she wasn't

happy. She had gained nearly one hundred pounds, and her hus¬

band often cruelly taunted her, telling her that she was "ugly” and

A PARADOX REVEALED

123

had a "fat ass.” She chafed too over how everybody in the system

treated her. "Recovery on the med model requires you to be obedi¬

ent, like a child," she explains. "You are obedient to your doctors,

you are compliant with your therapist, and you take your meds.

There's no striving toward greater intellectual concerns."

In 2005, she grew closer to a longtime friend, who was twenty

years older and belonged to a fundamentalist religious community.

She began attending their meetings, and they in turn began advising

her to dress, speak, and present herself to the world in a more for¬

mal way. "They told me, 'You are representing God, and you don't

want to bring shame to God,” she says. Kate's older friend also

urged her to stop thinking of herself as schizophrenic. "He's making

me think outside the box, and to think in ways that before I never

would have accepted. I would always defend my therapist, defend

my psychiatrist, defend the drugs, and defend my illness. He was

asking me to give up my identity as a mentally impaired person."

Soon, her old life fell completely apart. She discovered that her

husband had been sleeping with one of her friends, and after she

moved out of their apartment, she had to sleep for a time in her car.

Although at first, during that desperate time, she clung to her meds,

the nonschizophrenic vision of herself also beckoned, and in Febru¬

ary of 2006, she decided to take the leap: She would stop smoking,

she would stop drinking coffee, and she would wean herself from

her psychiatric medications. "Now I have no drugs, no nicotine,

and no coffee, and my body is going into shock. I am coming down

from all of this, and I am almost vibrating because I need my

cigarettes, my drugs."

This decision also put her at odds with most everyone in her life.

"I stopped talking to my family, because I didn't want to go back

into that identity [of a disabled person]. My mind was very delicate.

So I had to disengage from what I knew, and disengage from my

therapist." Soon, she was losing so much weight that her friends

thought she must be sick. As she struggled to stay sane, she clung to

the advice from her religious group, speaking to others in a very for¬

mal manner, and this behavior convinced her mother that she was

relapsing. "Strange ain't the word, honey" is how her mother puts

it, and even Kate privately feared that she was becoming psychotic

124

ANATOMY OF AN EPIDEMIC

again. "But I had this hope, this faith, and so I said to myself, 'I am

going to walk this tightrope across this horrible canyon, and hope¬

fully when I get to the other side, there will be a mountain ridge I

can stand on.' I had to focus on going forward regardless of where

it took me, because if I fell off the tightrope, I was back in the hos¬

pital."

It was at that perilous moment, when it seemed that she was

about to crash, that Kate agreed to meet her mother for dinner. "I

think she is having a breakdown," her mother says. "She sat very

proper, and looked scattered and disorganized. Her body was stiff. I

was seeing a lot of the same symptoms as before. Her eyes were di¬

lated and she seemed paranoid." As they drove away from the

restaurant, Kate's mother started to turn toward the hospital, but at

the last second she changed her mind. Kate "wasn't so crazy" that

she needed to be locked up. "I went home and cried,” her mother

remembers. "I didn't know what was happening."

By her mother's reckoning, it took Kate six months to get

through this withdrawal process. But she emerged on the other side

transformed. "I see that her face is so alive now and she is more

connected to her body,” her mother says. "She feels comfortable in

her own skin and more at peace with herself than ever. She is physi¬

cally healthy. I didn't know that this kind of recovery was possible."

In 2007, Kate married the older man who had encouraged her to go

this route; she also has thrived in her job as the manager of a home

for people with psychiatric problems, the company recognizing her

for her "outstanding” performance in 2008, an award that came

with a cash prize.

Kate does still struggle at times. The home she manages provides

shelter to several men who are sexual deviants— 'T've had people

say they are going to set me on fire, or they are going to pee in my

mouth," she says —and she no longer is having her emotional re¬

sponses to such stress numbed by medication. 'T've been off the

drugs for two years, and sometimes I find it very, very difficult to

deal with my emotions. I tend to have these rages of anger. Did the

drugs bring such a cloud over my mind, make me so comatose, that

I never gained skills on how to deal with my emotions? Now I'm

finding myself getting angrier than ever and getting happier than

A PARADOX REVEALED

•25

ever too. The circle with my emotions is getting wider. And yes, it's

easy to deal with when you're happy, but how do you deal with it

when you are mad? I'm working on not getting overly defensive,

and trying to take things in stride.”

Kate's story, of course, is idiosyncratic in kind. Her success at get¬

ting off meds does not mean that everyone can successfully with¬

draw from them. Kate is an amazing person —incredibly willful and

incredibly brave. Indeed, what the scientific literature reveals is that

once a person is on an antipsychotic, it can be very difficult and

risky to withdraw from the medication, and that many people suffer

severe relapses. But the literature also reveals that there are people

who can successfully withdraw from the medications and that it is

this group that fares best in the long term. Kate made it into that

group.

"That day in 2005 when I decided to get better, that's the divid¬

ing line in my life," she says. "I was a completely different person

then. I was very heavy, I smoked all the time, I had flat affect. Today

I run into people who knew me then, and they don't even recognize

me. Even my mother says, 'You are not the same person.' "

The Benzo Trap

"What seemed so good about the benzodiazepines

when I was playing with them was that it seemed like

we really did have a drug that didn't have many

problems. But in retrospect it's difficult to put a

spanner into a wristwatch and expect that it won't

do any harm."

— ALEC JENNER, BRITISH PHYSICIAN WHO

CONDUCTED FIRST TRIALS OF A BENZODIAZEPINE IN

THE UK (2003)

Fans of the cable television series Mad Men, which tells of the lives

of Don Draper and other Madison Avenue advertising men in the

early 1960s, may recall a scene from the last episode of season two,

when a friend of Draper's wife, Betty, says to her: "Do you want a

Miltown? It's the only thing keeping me from chewing my nails

off.” That was a nice, historically accurate touch, and if the creators

of Mad Men retain this period accuracy in season three and beyond,

which will tell the story of the ad men and their families during the

turbulent years of the mid-1960s, viewers can expect Betty Draper

and her friends to reach into their purses and make sly references to

"mother's little helper.” Hoffmann-La Roche brought Valium to

market in 1963, advertising it in particular to women, and from

1968 to 1981, it was the bestselling drug in the Western world. Yet,

as Americans gobbled up this pill designed to keep them tranquil,

something very odd happened: The number of people admitted to

mental hospitals, psychiatric emergency rooms, and mental health

outpatient clinics soared.

The scientific literature can explain why the two were linked.

THE BENZO TRAP

127

Anxiety Before Miltown

Although anxiety is a regular part of the human psyche, our minds

fashioned by evolution to worry and fret, there are some people who

are more anxious than others, and the notion that such emotional

distress is a diagnosable condition can be traced back to a New York

nerve doctor, George Beard. In 1869, he announced that dread,

worry, fatigue, and insomnia resulted from "tired nerves,” a physi¬

cal illness he dubbed "neurasthenia." The diagnosis proved to be a

popular one, this illness thought to be a by-product of the industrial

revolution that was sweeping America in the wake of the Civil War,

and naturally the market created a variety of therapies that could

restore a person's "tired” nerves. Makers of patent medicines sold

"nerve revitalizers" laced with opiates, cocaine, and alcohol. Neuro¬

logists touted the restorative powers of electricity, and this led those

diagnosed with neurasthenia to buy electric belts, suspenders, and

handheld massagers. Those who were wealthier could head to spas

that offered "rest cures," the patients' nerves restored through the

healing touch of soothing baths, massages, and various electric

gadgets.

Sigmund Freud provided psychiatry with a rationale for treating

this group of patients and, in so doing, enabled psychiatry to move

out of the asylum and into the office. Born in 1856, Freud set out

his shingle as a nerve doctor in Vienna in 1886, which meant that

many of his patients were women suffering from neurasthenia

(Beard's disease had become popular in Europe, too). After hours of

conversation with his clients, Freud became convinced that their

feelings of dread and worry were psychological in origin, rather

than the result of tired nerves. In 1895, he wrote about "anxiety

neurosis” in women, which he theorized arose in large part from

their unconscious repression of sexual desires and fantasies. Those

suffering from such psychological conflicts could find relief through

psychoanalysis, the patient on the couch led by the doctor into an

exploration of her unconscious mind.

At this time, psychiatry was a profession for those who treated

mad patients in the asylum. People with tired nerves went to see a

128

ANATOMY OF AN EPIDEMIC

nerve doctor or a general practitioner for help. But if anxiety arose

from a psychological disorder in the brain, rather than from a fraz¬

zling of the nerves, then it made sense that psychiatrists could tend

to these patients, and after Freud visited America in 1909, psycho¬

analytic societies began to form, with New York City the hub of this

new therapy. Nationwide, only 3 percent of psychiatrists were in pri¬

vate practice in 1909; thirty years later, 38 percent were seeing pa¬

tients in private settings. 2 Moreover, Freudian theory made nearly

everyone a candidate for the psychiatrist’s couch. "Neurotics," Freud

explained during his 1909 tour, "fall ill of the same complexes with

which we sound people struggle." 3

Thanks to Freudian theories, psychiatric disorders were now di¬

vided into two basic categories: psychotic and neurotic. In 1952, the

American Psychiatric Association published the first edition of its

Diagnostic and Statistical Manual, and it described the neurotic pa¬

tient in this way:

The chief characteristic of [neurotic] disorders is "anxiety,”

which may be directly felt and expressed or which may be un¬

consciously and automatically controlled by the utilization of

various psychological defense mechanisms. ... In contrast to

those with psychoses, patients with psychoneurotic disorder

do not exhibit gross distortion or falsification of external re¬

ality (delusions, hallucinations, illusions) and they do not

present gross disorganization of the personality. 4

Such was the understanding of anxiety when Miltown came

to market. Anxious people had their feet firmly planted in reality,

and rarely was anxiety a condition that required hospitalization.

In 1955, there were only 5,415 "psychoneurotic" patients in state

mental hospitals. 5 As Stanford psychiatrist Leo Flollister confessed

after the benzodiazepines were introduced, these drugs were "de¬

signed to treat what many would regard as a 'minor disorder.' " 6

The drugs were a balm for the "walking wounded," and thus, as we

review the outcomes literature for the benzodiazepines, we should

expect this patient group to function well. After all, that was the fu¬

ture promised by Miltown inventor Frank Berger: "Tranquilizers,

THE BENZO TRAP

I 2 9

by attenuating the disruptive influence of anxiety on the mind, open

the way to a better and more coordinated use of the existing gifts,”

he said. 7

The Minor Tranquilizers Fall from Grace

When Miltown first appeared, there were a number of studies pub¬

lished in medical journals that told —as two Harvard Medical

School researchers, David Greenblatt and Richard Shader, later re¬

called—of how it "was almost magically effective in reducing anxi¬

ety.” But as has often been the case in psychiatry, once a successor

pill appeared on the market (Librium, in 1960), the efficacy of the

old drug suddenly began to fade. In their review of the Miltown lit¬

erature in 1974, Greenblatt and Shader found that in twenty-six

well-controlled trials, there were only five in which Miltown "was

more effective than placebo" as a treatment for anxiety. Nor was

there any evidence that Miltown was better than a barbiturate in

calming the nerves. The initial popularity of this drug, they wrote,

"illustrates how factors other than scientific evidence may deter¬

mine physicians' patterns of drug use." 8

However, Miltown's fall from favor with the public arose from a

different problem than lack of scientific efficacy. Many who tried

the drug found that they became sick when they stopped taking it,

and in 1964, Carl Essig, a scientist at the Addiction Research Cen¬

ter in Lexington, Kentucky, reported that it "could induce physical

dependence in man." 5 Science News quickly announced that the

happy pill could be "addictive,” and on April 30, 1965, Time all

but buried Miltown. There is "a growing disillusionment with Mil-

town on the part of many doctors," the magazine wrote. "Some

doubt that it has any more tranquilizing effect than a dummy sugar

pill. ... A few physicians have reported that in some patients, Mil-

town may cause a true addiction, followed by withdrawal symp¬

toms like those of narcotics users 'kicking the habit.' " I0

Publicly, the benzodiazepines mostly escaped this opprobrium

during the 1960s. When Hoffmann-La Roche brought Librium to

130

ANATOMY OF AN EPIDEMIC

market in 1960, it claimed that its drug provided "pure anxiety re¬

lief,” and unlike Miltown and the barbiturates, was "safe, harmless

and non-addicting." That belief took hold and the FDA did little to

counter it, even though very early on it started receiving letters from

people who were experiencing odd and quite distressing symptoms

when they tried to quit a benzodiazepine. They told of awful insom¬

nia, anxiety more severe than they had known before, and a rash of

physical symptoms —tremors, headaches, and nerves that "jangled

like crazy." As one man wrote the FDA, "I was not sleeping and in

general felt horrible. Sometimes I thought I would die and other

times wished I had.” 11 Although the FDA held a hearing on the mat¬

ter, it did not impose any legal control on benzodiazepines similar to

what had been placed on amphetamines and barbiturates, and so

the public's belief that the drugs were relatively nonaddictive and

harmless survived until 1975, when the U.S. Justice Department de¬

manded that they be classified as schedule IV drugs under the Con¬

trolled Substances Act. This designation limited the number of

refills a patient could obtain without a new prescription, and re¬

vealed to the public that the government had concluded that benzo¬

diazepines were, in fact, addictive.

"Danger ahead! Valium —The Pill You Love Can Turn on You,”

a Vogue headline screamed. A benzodiazepine, the magazine ex¬

plained, could lead to a "far worse addiction than heroin." 12 The

Valium backlash had begun, particularly in the pages of women’s

magazines, and soon Ms. magazine provided readers with first-

person accounts of the horrors of withdrawing from it. "My with¬

drawal symptoms are a double-dose of the anxiety, irritableness,

and insomnia I used to feel," one user said. Confessed another: "I

can't begin to describe the physical and mental anguish that accom¬

panied my withdrawal." 19 The happiness pill of the 1950s was turn¬

ing into the misery pill of the 1970s, with the New York Times

reporting in 1976 that "some critics go so far to say that [Valium] is

doing more harm than good, or even deny that it is doing any good

at all for the great majority of patients. Some cry with alarm that it

is far from being as safe as it is proclaimed, that it can be hideously

and dangerously addictive, and may be the direct cause of addicts'

deaths." 14 Two million Americans were said to be addicted to

THE BENZO TRAP

• 131

benzodiazepines, four times the number of heroin addicts in the

country, and one of the pill takers turned out to be former first lady

Betty Ford, who checked herself into an alcohol and drug rehab

center in 1978. Abuse of tranquilizers, said her physician Joseph

Pursch, was "the nation's number one health problem." 15

Over the next few years, the benzodiazepines officially fell from

grace. In 1979, Senator Edward Kennedy held a Senate Health Sub¬

committee hearing on the dangers of benzodiazepines, which he said

had "produced a nightmare of dependence and addiction, both very

difficult to treat and recover from." 15 After reviewing the scientific

literature, the White House Office of Drug Policy and the National

Institute of Drug Abuse concluded that the drugs' sleep-promoting

effects didn't last more than two weeks, and this finding was soon

seconded by the Committee on the Review of Medicines in the

United Kingdom, which found that the drugs' anti-anxiety effects

didn't last beyond four months. As such, the committee recom¬

mended that "patients receiving benzodiazepine therapy be carefully

selected and monitored and that prescriptions be limited to short¬

term use."” As an editorial in the British Medical Journal put it:

"Now that benzodiazepines have been shown to cause drug

dependence should their use be more closely controlled —or even

banned?" 18

The ABCs of Benzodiazepines

This story of the benzodiazepines' fall from grace might seem like

ancient history, a footnote in our quest to understand why there has

been such a rise in the number of disabled mentally ill in the United

States over the past fifty years, except for the fact that the benzodi¬

azepines never really went away. Although the number of prescrip¬

tions for benzodiazepines dropped after they were classified as

schedule IV drugs, from 103 million in 1975 to 71 million in 1980,

the following year Upjohn brought Xanax to market, and this

helped stabilize sales of benzodiazepines.” Psychiatrists continued

to prescribe benzodiazepines to many of their nervous patients, and

in 2002, Stephen Stahl, a well-known psychopharmacologist at the

13 2

ANATOMY OF AN EPIDEMIC

University of California in San Diego, confessed to psychiatry's

dirty little secret in an article titled "Don't Ask, Don't Tell, But

Benzodiazepines Are Still the Leading Treatments for Anxiety Dis¬

orders." 20 Since that time, the prescribing of benzodiazepines in the

United States has increased, from 69 million prescriptions in 2002

to 83 million in 2007, which isn't all that far below the number

written at the height of the Valium craze in 1973. 21

So, given that benzodiazepines have been widely used for fifty

years, we need to look at what science has to tell about these drugs,

and whether their use may be contributing in some way to the in¬

crease in the number of disabled mentally ill in the United States.

Short-term efficacy

As anyone who has taken a benzodiazepine can attest, it acts rap¬

idly, and if a person hasn't become habituated to the drug, it will

numb his or her emotional distress. As such, a benzodiazepine has

an obvious utility in helping people through a situational crisis. The

writer Andrea Tone, in her book The Age of Anxiety, relates how a

benzodiazepine enabled her to get on an airplane after she some¬

what mysteriously developed a fear of flying. But as clinical trials re¬

vealed, that immediate efficacy quickly begins to fade and pretty

much disappears by the end of four to six weeks.

In 1978, Kenneth Solomon at Albany Medical College in New

York reviewed seventy-eight double-blind trials of benzodiazepines

and determined that the drugs had proved to be significantly better

than a placebo in only forty-four of them. At best, the collective re¬

sults could be said to "hint at therapeutic efficacy," he wrote. 22 Five

years later, Arthur Shapiro at Mt. Sinai School of Medicine in New

York City fleshed out this efficacy picture a bit more, reporting that

in a trial of 224 anxious patients, Valium proved superior to a

placebo for the first week, but then this advantage began to lessen.

Based on the patients' self-assessment of their symptoms, by the end

of the second week there was no difference between the drug and a

placebo, and by the end of six weeks, the placebo group was faring

slightly better. "It is unlikely in our opinion that carefully controlled

THE BENZO TRAP

133

studies would consistently show significant benzodiazepine thera¬

peutic antianxiety effects," Shapiro wrote. 23

That picture of the short-term efficacy of benzodiazepines has

not markedly changed since then. The drugs show clear efficacy for

the first week, and then their advantage over a placebo abates. But,

as British investigators noted in 1991, this brief period of efficacy

comes at a fairly high cost. "Both psychomotor and cognitive func¬

tioning may be impaired, and amnesia is a common effect of all ben¬

zodiazepines," they said. 24 In 2007, researchers in Spain looked at

whether these adverse events negated the small "efficacy benefit"

provided by the drugs, and found that the drop-out rates in clinical

trials, a measure often used to assess the overall "effectiveness" of a

drug, were the same for benzodiazepine and placebo patients. "This

systematic review did not find convincing evidence of the short-term

effectiveness of the benzodiazepines in the treatment of generalized

anxiety disorder," they reported. 25

Malcolm Lader, a psychiatrist at the Institute of Psychiatry in

London who is one of the world's leading experts on benzodi¬

azepines, explained the importance of this finding in an interview:

"Effectiveness is a measure of what it's like in real practice." 26

Withdrawal syndromes

Although the first report of benzodiazepine dependence appeared in

the scientific literature in 1961, when Leo Hollister at Stanford Uni¬

versity reported that patients withdrawing from Librium were expe¬

riencing odd symptoms, it wasn't until the Justice Department

classified benzodiazepines as schedule IV drugs that researchers

began investigating the problem with any vigor. In 1976, physicians

Barry Maletzky and James Kotter jump-started this inquiry, re¬

porting that when their patients stopped taking Valium, many

complained of "extreme anxiety." 27 Two years later, physicians at

Pennsylvania State University announced that patients withdrawing

from benzodiazepines often experienced "an increase in anxiety

above baseline levels ... a condition that we term 'rebound anxi¬

ety.' " 2S In Britain, Lader reported similar findings. "Anxiety rose

1 3 4

ANATOMY OF AN EPIDEMIC

In this 1 985 study by British investigators, the patients treated with Valium did not fare better

than the placebo patients during the first six weeks. The Valium patients were then withdrawn

from the drug and their anxiety symptoms soared, to a much higher level than the symptoms

in placebo patients. Source: Power, K. "Controlled study of withdrawal symptoms and rebound

anxiety after six week course of diazepam for generalised anxiety." British Medical Journal 290

(1 985): 1 246-48.

sharply during withdrawal, and to a point of panic in several pa¬

tients. Patients commonly experienced bodily symptoms of anxiety,

such as a choking feeling, dry mouth, hot and cold, legs like jelly,

etc.

Patients withdrawing from benzodiazepines, it seemed, were be¬

coming more anxious than they had ever been. Over the course of

the next decade, Lader and other British physicians (most notably

Heather Ashton, a doctor at the University of Newcastle upon Tyne

who ran a withdrawal clinic) continued to investigate this problem,

and they compiled a long list of symptoms that could bedevil those

quitting a benzodiazepine. In addition to rebound anxiety, patients

could experience insomnia, seizures, tremors, headaches, blurred vi¬

sion, a ringing in the ears, extreme sensitivity to noise, a feeling that

insects were crawling over them, nightmares, hallucinations, ex¬

treme depression, depersonalization, and derealization (a sense that

the external world is unreal). Withdrawal, one patient told Heather

Ashton, was like "living death ... I thought I had gone mad.”

"These findings show very clearly that benzodiazepine withdrawal

THE BENZO TRAP

135

is a severe illness,” Ashton wrote. "The patients were usually fright¬

ened, often in intense pain, and genuinely prostrated. . . . Through

no fault of their own, the patients suffered considerable physical as

well as mental distress." 30

Not all people withdrawn from benzodiazepines suffer in this

way. The risk of suffering withdrawal symptoms varies according to

how long a person has been on the drug, the potency of the benzodi¬

azepine, and the speed of the drug-tapering process. A majority of

patients who've taken a benzodiazepine for a relatively short time,

such as a month or two, may be able to withdraw from it with little

difficulty. However, some people experience withdrawal symptoms

after taking a benzodiazepine for only a few weeks, and it can take a

longtime user a year or longer to taper from the drug. Moreover, a

small percentage of people suffer a "protracted withdrawal syn¬

drome," their anxiety remaining at elevated levels "for many months

after benzodiazepine withdrawal," Ashton observed. 31 Depression

may deepen, and the odd perceptual symptoms —the depersonaliza¬

tion, the derealization, the sensation of insects crawling on the

skin —can haunt a person for an extended period. Most alarming, a

small percentage of long-term users never fully recover. "It is very

worrying," Lader said, in an interview. "Somehow there has been a

change [in the brain], I cannot say that everybody is going to recover

back to normality when they come off long-term usage.”

The biology of benzodiazepine withdrawal

In 1977, researchers discovered that benzodiazepines affect a neuro¬

transmitter in the brain known as GABA. Unlike dopamine and

serotonin, which transmit an "excitatory" message telling a neuron

to fire, GABA (gamma-aminobutyric acid) inhibits neuronal activ¬

ity. A neuron receiving the GABA message either fires at a slower

rate or stops firing for a period of time. A majority of neurons in the

brain have GABA receptors, which means that this neurotransmit¬

ter acts as the brain's brake on neuronal activity. A benzodiazepine

binds to the GABA receptor and, in so doing, amplifies GABA's in¬

hibitory effects. It pushes down on the GABA brake, so to speak,

and as a result, it suppresses central nervous system activity.

1 3 6

ANATOMY OF AN EPIDEMIC

In response, the brain decreases its output of GABA and de¬

creases the density of its GABA receptors. It is trying to "restore

normal GABA transmission," British scientists explained in 1982. 32

However, as a result of these adaptive changes, the brain's braking

system is now in a physiologically impaired state. Its braking fluid is

low (GABA output), and its brake pads are worn (GABA receptors).

As a result, when the benzodiazepine is withdrawn, the brain is no

longer able to properly inhibit neuronal activity, and its neurons

may begin firing at a helter-skelter pace. This overactivity, Heather

Ashton concluded, may "account for many of the effects of with¬

drawal."" The anxiety, the insomnia, the sensation of insects crawl¬

ing across the skin, the paranoia, the derealization, the seizures —all

of these vexing symptoms may arise from neuronal hyperactivity.

If a person gradually tapers off from a benzodiazepine, the

GABA system may slowly revert to normal, and thus withdrawal

symptoms may be mild. However, the fact that some long-term

users suffer "protracted symptoms" is probably "due to the failure

of the [GABA] receptors to revert to their normal state," Ashton

said. 34 Long-term benzodiazepine use, she explained, may "give rise

not only to slowly reversible functional changes in the central ner¬

vous system, but may also occasionally cause structural neuronal

damage.” 35 In such cases, the GABA brake never again functions

like it should.

Long-term effects

Once researchers in the United States and the United Kingdom de¬

termined that benzodiazepines did not provide any durable relief

from anxiety, an obvious question arose: Do these drugs, when

taken on a continual basis, worsen the very symptom they are sup¬

posed to treat? In 1991, Karl Rickels at the University of Pennsyl¬

vania School of Medicine reported on a group of anxious patients

who had tried to quit benzodiazepines three years earlier, and he

found that those who had successfully gotten off the drugs were

doing "significantly" better than those who had failed to do so. 35 A

few years later, he was back with a new study: When long-term

THE BENZO TRAP

137

users withdrew from benzodiazepines, they "became more alert,

more relaxed, and less anxious, and this change was accompanied

by improved psychomotor functions." 97 Those who stayed on the

benzodiazepines were more emotionally distressed than those who

got off.

Others told of similar long-term results. Canadian investigators

found that benzodiazepine usage led to a fourfold increase in de¬

pressive symptoms. 3 ' In England, Ashton observed that those who

stay on the drugs tend to became more ill: "Many patients find that

anxiety symptoms gradually increase over the years despite continu¬

ous benzodiazepine use, and panic attacks and agoraphobia may

appear for the first time." 33 These studies and observations told of a

very problematic long-term course, and in 2007, French researchers

surveyed 4,425 long-term benzodiazepine users and found that 75

percent were "markedly ill to extremely ill ... a great majority of

the patients had significant symptomatology, in particular major de¬

pressive episodes and generalized anxiety disorder, often with

marked severity and disability." 40

In addition to causing emotional distress, long-term benzodi¬

azepine usage also leads to cognitive impairment. Early on, re¬

searchers recognized that memory problems were associated with

short-term use, and this led David Knott, a physician at the Univer¬

sity of Tennessee, to warn in 1976 that "I am very convinced that

Valium, Librium and other drugs of that class cause damage to the

brain. I have seen damage to the cerebral cortex that I believe is due

to the use of these drugs, and I am beginning to wonder if the dam¬

age is permanent." 41 Over the next twenty-five years, reports of cog¬

nitive impairment in long-term benzodiazepine users regularly

appeared in scientific journals. These studies told of people who

were having trouble focusing, remembering things, learning new

material, and solving problems. However, the patients "are not

aware of their reduced ability," Lader wrote, evidence that their

self-insight was impaired as well. 43 In 2004, a group of Australian

scientists, after reviewing the relevant literature, concluded that

"long-term benzodiazepine users were consistently more impaired

than controls across all cognitive categories," with these deficits

1 3 8

ANATOMY OF AN EPIDEMIC

"moderate to large” in magnitude. The studies showed the "higher

the intake, dose and period of use [of a benzodiazepine], the greater

the risk of impairment." 43

Increased anxiety, increased depression, and cognitive impair¬

ment-all of these factors contribute to a decline in a person's abil¬

ity to function in society. In 1983, the World Health Organization

noted a "striking deterioration in personal care and social inter¬

actions" in long-term benzodiazepine users. 44 Another investigator

reported that they end up with poor coping skills. 45 In a study

funded by Hoffmann-La Roche, the manufacturer of Valium, Uni¬

versity of Michigan investigators determined that taking this drug

was "associated with poor quality of life, poor performance in

work and personal life, low social support, perceived lack of inter¬

nal control, poor perceived health and high levels of stress." 46 Ashton

determined that long-term use led to "malaise, ill-health, and ele¬

vated scores for neuroticism." 47 Benzodiazepines, she said, contribute

to "job loss, unemployment, and loss of work through illness." 48

Such is the history told about benzodiazepines in the scientific litera¬

ture. Moreover, it is a story easily traced, as Dr. Stevan Gressitt, who

today is the medical director for Adult Mental Health Services in

Maine, can attest. In 2002, he helped form the Maine Benzo Study

Group, which was comprised of physicians and other health-care

professionals, and it concluded that "there is no evidence support¬

ing the long-term use of benzodiazepines for any mental health con¬

dition." Benzodiazepines, Gressitt and his colleagues wrote, may

"aggravate” both "medical and mental health problems.” In an in¬

terview, I asked Dr. Gressitt whether those "problems" included

increased anxiety, cognitive impairment, and functional decline. Was

his understanding of the scientific literature, I wondered, the same as

mine?

"Your words I don't contradict or argue with," he replied. 49

THE BENZO TRAP

139

Geraldine, Hal, and Jill

The scientific literature reveals that benzodiazepines —much as the

neuroleptics do —act like a trap. The drugs ameliorate anxiety for a

short period of time, and thus they can provide a distressed person

much needed relief. However, they work by perturbing a neuro¬

transmitter system, and in response, the brain undergoes compensa¬

tory adaptations, and as a result of this change, the person becomes

vulnerable to relapse upon drug withdrawal. That difficulty in turn

may lead some to take the drugs indefinitely, and these patients are

likely to become more anxious, more depressed, and cognitively

impaired.

Here are the stories of three people who fell into the trap.

Geraldine Burns, a thin woman with dark red hair, still lives in the

house she grew up in. She tells me her story while we sit in her

kitchen, her elderly mother darting in and out.

Born in 1955, Geraldine was one of six children, and theirs was a

happy family. Her father was Irish, her mother Lebanese, and their

Boston neighborhood was known as "Little Lebanon,” a place

where everybody definitely knew your name. Aunts, uncles, and

other relatives lived nearby. At age eighteen, Geraldine started dat¬

ing a boy who lived down the block, Joe Burns. "I've been with him

ever since," she says, and for a time their life unfolded just as Geral¬

dine had hoped. She had a job that she enjoyed in human resources

at a rehabilitation center, she and Joe had a healthy son (Garrett) in

1984, and they basked in their close-knit neighborhood. Geraldine —

outgoing and energetic —was the constant hostess for gatherings of

family and friends. "I loved my life,” she says. "I loved working, I

loved my family, and I loved this neighborhood. I was the one who

organized the reunion of my grammar school. I still had friends

from kindergarten. I couldn't have been more normal."

However, in March 1988, Geraldine gave birth to a daughter,

Liana, and she felt physically unwell afterward. "I kept telling the

doctors and nurses that I felt like I weighed a thousand pounds,”

140

ANATOMY OF AN EPIDEMIC

she says, and after a doctor ruled out an infection, he figured she

must be anxious and prescribed Ativan. Geraldine came home from

the hospital with a prescription for that benzodiazepine, and al¬

though it helped for a short while, months later she still felt some¬

thing wasn't right and so she went to see a psychiatrist. "She

immediately tells me I have a chemical imbalance," Geraldine re¬

calls. "She says that I should keep taking the Ativan and assures me

that it is harmless and nonaddictive. She tells me that I will have to

take this drug for the rest of my life. Later, when I questioned her

about this, she explained it this way: 'If you were a diabetic you

would have to take insulin for the rest of your life, wouldn't you?' "

Soon her psychiatrist added an antidepressant to the Ativan, and

as Geraldine struggled to take care of her daughter that first year,

her emotions seemed numbed, her mind fogged. "I was in a daze

half the time. My mother would call and I would tell her something,

and she would say, 'You told me that last night.' And I'd say, 'I

did?' " Worse, as the months wore on, she found herself becoming

ever more anxious, so much so that she started staying inside her

house. Going back to her job in human resources at the rehabilita¬

tion center was now out of the question. At one point, after she

stopped taking Ativan for a day or two, she had a "massive panic

attack." The federal government agreed that she was disabled by

"anxiety" and thus eligible for a monthly SSDI payment. "Me, who

was the most social person on the planet, is not able to go out,"

Geraldine says, shaking her head in disbelief. "I wouldn't go out un¬

less my husband would take me."

Over the next eight years, Geraldine cycled through an endless

combination of anti-anxiety and antidepressant medications. None

worked. The anxiety and panic remained, and she suffered from a

medley of side effects —rashes, sexual dysfunction, weight gain,

tachycardia (from the panic attacks), and excessive menstrual bleed¬

ing, the last leading to a hysterectomy. "All of the women I've

known who were on Ativan long-term ended up having a hysterec¬

tomy, every single one of us," she says, with evident bitterness. At

last, in October 1996, she went to a new physician, who, after re¬

viewing her medical history, identified a likely culprit. "He told me,

'You are on one of the most addictive drugs known,' and I thought,

THE BENZO TRAP

141

'Thank God.' I was in tears. It was the drugs all along. I had been

made iatrogenically ill."

Geraldine spent two nightmarish years withdrawing from Ativan

and the other psychiatric drugs she had been taking. Horrible smells

came from her body, her muscles twitched, she lost weight, and at

one point, she couldn't sleep for weeks. "It was like hell opened up

and swallowed me in," she says. Although she did kick the habit, it

took several more years for her to feel better physically, and she still

suffers from a great deal of anxiety. The gregarious, socially-at-ease

person she had always been before that fateful day in March 1988

when she was prescribed Ativan has never returned. "Am I back to

my old self? No," she whispers. "I mourn who I used to be. We all

mourn. I am still so afraid of so many things."

Three days before I was to meet with Hal Flugman, who lives in

South Florida, he called to say that his anxiety had flared up again,

and the thought of leaving his house to talk to me was too stressful.

"I am not feeling right," he said. "I'm over-breathing, I have these

terrible gastrointestinal problems. I think I have to get my Klonopin

dose upped. . . . This is what is happening to me.”

Hal, whom I'd interviewed by phone a few months earlier, first

became anxious when he was thirteen years old. Overweight and

small, he didn't get along well with his classmates in middle school.

"I had panic attacks, and a slight fear of being around people," he

recalls. For the next five years, he went to counseling, but he was

not prescribed a medication. "I was living with it, dealing with it,”

he says, but then one night at a rock concert, the panic hit so hard

that he had to call his family and beg that they come get him. The

following day a doctor gave him a prescription for Klonopin.

"I remember saying to the doctor, 'Am I going to become ad¬

dicted and have a really hard time coming off?' I was worried about

the side effects, too. But the doctor said that the side effects would

go away in a couple of weeks, and didn't that beat living with these

unbearable panic attacks? I said, 'Well, of course.' And I knew from

the first pill that this was going to solve my anxiety problem. It

absolutely worked for me. I felt great.”

142

ANATOMY OF AN EPIDEMIC

Hal's life since then is a story of addiction. Shortly after going on

the drug, he moved to San Francisco to pursue a career as a musi¬

cian, and for a time it went well —he even got to hang out with Car¬

los Santana, the great guitarist. But his music career failed to take

off, and today he thinks that the Klonopin was partly to blame, for

it stifled his ambition and didn't help his finger dexterity, either.

Eventually, he fell into a deep depression — "I felt like a zombie," he

says —and at age twenty-nine he returned to Florida to live with his

parents. At that point, he was diagnosed with bipolar illness, the

government agreeing that he was so disabled by mental illness that

he was eligible to receive SSI. The years slid by, his mother passed

away, and then, in 2001, he began taking higher doses of Klonopin,

as otherwise his depression would become unbearable. His doctor

told him he was abusing the drug and sent him to a detox facility,

where, over a period of ten days, he was withdrawn from the ben¬

zodiazepine he had been taking for sixteen years.

"What happened next was absolutely the worst thing in my life,"

he says. "I could give you a list of symptoms, but that wouldn't do

justice to what I was going through mentally. Month after month I

got worse and worse. I couldn't sleep, and the symptoms —the most

debilitating one was this feeling that I was dead. I felt that my brain

was ripped out of my head, like I wasn't even a living thing. I had

depersonalization, my skin felt weird, my body felt weird. I didn't

even want to get into the shower. Even room-temperature water felt

strange on my skin. If I put on mildly hot water, it felt like it was

burning right through me. I couldn't digest food right, I couldn't go

to the bathroom for weeks at a time, I couldn't urinate right ... I

was in a constant state of panic attacks, and this doctor is telling me

it's all in my mind, that he won't write me a script, and that with¬

drawal symptoms can last a maximum of thirty days. I was cracking

up, going insane.”

This went on for ten months. He found Geraldine Burns on the

Internet, as she had started a benzodiazepine support group, and

she would console him for hours at a time. Ten, twenty times a

night he would call his sister Susan, screaming that he was going to

kill himself. He desperately sought to get a new prescription for

Klonopin, but the doctors he saw didn't believe that his torment

THE BENZO TRAP

143

was related to benzodiazepine withdrawal. Instead, they figured

that he had abused the drug in the past and so they refused to put

him back on it. "They don't understand that the drug changes the

whole biology of your brain, and that your brain doesn't work right

anymore,” Hal says. Finally, his sister found a physician who agreed

to write him a script, and "within hours, the nightmare was over.

Every single side effect, every single withdrawal problem I had been

going through was gone. Completely. Like magic. I was jumping up

and down I was so excited.”

Hal has never tried going off Klonopin again. His brain adapted

to the drug, he says, and now it can't adapt back. "Klonopin ruined

my life. It takes away your drive, and in the morning, you don't

want to get out of bed, because you feel so groggy. I don’t even

know what it's like to feel normal. This is my world. Things don't

get me as excited as most people because I'm in a constant state of

sedation. It should never have been prescribed for long-term use.”

Susan sees it much the same way. "My sister and I have talked at

length about how our brother is very good-looking, and how when

he is acting normal, you would not know there is anything wrong,"

she says. "He is adorable, charming; he carries on conversations.

He could have been with a nice woman and had a family. But now?

He has no friends. None whatsoever. He stays at home most of the

time, except when he has to go to the store. He is trapped. He can't

get off Klonopin. I feel terrible for him, and I feel terrible for my

dad, who when he dies will never have seen his son do well. It kills

us that he could have had a life."

If a picture is worth a thousand words, the photos that Jill, an Ohio

woman in her mid-thirties, sends me tell her story in a very succinct

fashion. There is the "before” photo in which she is smiling and

looking confidently into the camera, posed like a model in a fashion¬

able black dress. One hand is posed gracefully on her hip, a pearl

necklace adds a touch of elegance, and she is a bit dolled up —the

makeup and styled black hair tell of a woman who presents herself

carefully to the world. And then there is the "after” photo, her eyes

hollowed out and bloodshot, her face taut and drawn, her hair

144

ANATOMY OF AN EPIDEMIC

thinned—she looks like a somewhat crazed methamphetamine

addict who is now getting her photo taken following an arrest.

We first spoke on the phone in July of 2008, three months after

she had taken her last dose of a benzodiazepine, a drug she had

been on for thirteen years. Here's how she starts her story: "My

head is feeling crushed. It's like horses are kicking my skull."

Jill, who asked that I not use her last name, grew up in an afflu¬

ent suburb of Columbus, Ohio, where she attended private schools

and excelled in multiple ways. She sang competitively, won school

awards for her art, and was a top student. Petite and pretty, she was

asked by a representative of the Miss Ohio pageant to enter that

competition. "I was a vibrant, creative, fun person,” she says. How¬

ever, she did occasionally struggle with anxiety and depression, and

during her sophomore year at Ohio State University a psychiatrist

put her on an antidepressant. Unfortunately, that drug seemed to

increase her anxiety, and so eventually the psychiatrist added

Klonopin to the mix. "He said it was a gentle little pill used to help

old ladies sleep. He said that it wasn't addictive and that if I wanted

to stop, at most I'd experience a few nights of bad sleep. But he said

I would probably need to take it for life, just like a diabetic needs

insulin."

For the next ten years, Jill functioned okay. She graduated

summa cum laude from Ohio State University in 1996, earned a

master's degree in counseling, and after various adventures, in 2002

she began teaching fourth grade in a public school. However,

throughout this period, her anxiety returned again and again, and

each time it did, her psychiatrist upped her dose of Klonopin. And

as the dose increased, her ability to function declined. "I would

wonder, What is wrong with me? Why am I becoming so with¬

drawn? Why am I losing interest in everything? I was getting sicker

and sicker.” Then, in late 2004, the anxiety, panic, and depression

returned worse than ever, and new symptoms —obsessions and sui¬

cidal ideation —appeared too. She was told this meant she was

"bipolar" and she was prescribed an antipsychotic, Abilify. "That's

when I flipped out. My anxiety went through the roof, it was like

being injected with stimulants, and I was teaching one day and I

THE BENZO TRAP

145

started crying in class. I couldn't take it anymore, and I was hospi¬

talized in a psychiatric ward.”

Now came the drug merry-go-round. During the next two years,

Jill was put on Lamictal, Lexapro, Seroquel, Neurontin, lithium,

Wellbutrin, and other drugs she can't remember, with Klonopin al¬

ways part of the cocktail. This treatment caused her eyes to swell,

her skin to break into rashes, and her eyebrows and hair to fall out.

"My poor brain was being treated like a mixing bowl," she says.

Only when she asked doctors whether the cocktail might be making

her sick, "they would say, 'We have tried the drugs and they are not

helping, and so the problem is you.' " Indeed, since the drugs

weren't working, her psychiatrists gave her electroshock, which

took its toll on her memory.

Growing ever more desperate, toward the end of 2006 Jill con¬

cluded that "it was the drugs that were making me sick.” She began

withdrawing from the medications one by one, and although she

was able to get off the antidepressants and antipsychotics, every

time she tried tapering off Klonopin she suffered a long list of tor¬

ments: hallucinations, horrible anxiety, vertigo, painful muscle

spasms, perceptual distortions, and derealization, just to name a

few. Finally, in the spring of 2008, she adopted a new strategy: She

would get off by progressively switching to less potent benzodi¬

azepines. Klonopin was replaced by Valium, the Valium by Librium,

and then, in April 2008, she withdrew from Librium. She was now

drug free, yet three months later, when I spoke to her on the phone,

she was still in withdrawal torment. "What I've been through . . .

the trauma," she says, breaking into tears. "I feel dizzy all the time.

It is like the floor is tilting one way and I am spinning the other

way. It is horrific. I have had hallucinations, I have to wear sun¬

glasses in the house, sometimes I scream from the pain."

At the end of our interview, I asked her to think back to what her

life had been like before she was put on a benzodiazepine, and once

more she began to cry.

"My anxiety then was like a mild case of asthma, and today it's

like I have end-stage lung disease. I'm terrified that I'm not going to

make it. I'm so, so scared.”

146

ANATOMY OF AN EPIDEMIC

Those interviews provide a snapshot of three lives, and several

months later I spoke to each of the subjects again to see if anything

had changed. Geraldine was doing much the same. Hal had become

much more distraught. The Klonopin no longer seemed to be work¬

ing, his anxiety had returned with a vengeance, and he felt physi¬

cally sick. "I've come to accept this is my life," he said, his voice

filled with what seemed like bottomless despair. There was, how¬

ever, an encouraging postscript to Jill's story. Not long after our

phone interview, her withdrawal symptoms began to abate, and in

early 2009, she had this to report: The hallucinations, the vertigo,

the seizures, the hair loss, and the blurry vision had all disappeared.

The muscle spasms, the tinnitus, and the hypersensitivity to light

and noise had become less severe. The feeling that her head was

"packed in cement" had lessened.

"I have a few good days now, and my bad days are not all that

bad anymore,” she says. "I think I can see the light at the end of the

tunnel. There is no doubt I am going to be better. I am going to

move to Boston, and although I'll have to start from scratch, I know

it will be okay. I now value life like nobody else I know. I enjoy

being able to walk in a straight line again, and being able to see

again, and even having a normal heartbeat. My hair is beginning to

come back. I am getting better; I am just waiting for the cement to

completely leave my brain."

The Disability Numbers

At least to a degree, we can track the toll that the anti-anxiety drugs

have taken over the past fifty years. As was noted at the beginning

of this chapter, once the Miltown craze erupted, the number of peo¬

ple turning up at mental hospitals, outpatient centers, and residen¬

tial facilities for the mentally ill began to sharply rise. The U.S.

Department of Health and Human Services dubs this number "pa¬

tient care episodes,” and it soared from 1.66 million in 1955 to 6.86

THE BENZO TRAP

147

million in 1975, when Valiumania was near its peak. 50 On a per-

capita basis, that was an increase from 1,028 patient-care episodes

per 100,000 people to 3,182 per 100,000, a threefold jump in

twenty years. While many factors may have contributed to that in¬

crease (the emotional struggles that some Vietnam veterans experi¬

enced is one possibility that comes to mind, and illicit drug use is a

second), Valiumania was clearly a major one. In the late 1970s,

Betty Ford's physician, Joseph Pursch, concluded that benzodi¬

azepines were the "nation's number one health problem," and that

was because he knew they were driving people to detox centers,

emergency rooms, and psychiatric wards.

As the personal stories of Geraldine, Hal, and Jill attest, benzodi¬

azepines continue to be a pathway to disability for many. These

three are part of the surge of people with an "affective disorder"

who have swelled the SSI and SSDI rolls in the past twenty years.

Although the Social Security Administration doesn't detail the

number of disabled mentally ill who have anxiety as a primary di¬

agnosis, a 2006 report by the U.S. General Accountability Office

provides a proxy for estimating that number. It noted that 8 percent

of the younger adults (eighteen to twenty-six years old) on the SSI

and SSDI rolls were disabled by anxiety, and if that percentage

holds true for all ages, then there were more than 300,000 adults in

the United States who received government support in 2006 due to

an anxiety disorder. 51 That is roughly sixty times the number of psy¬

choneurotics hospitalized in 1955.

Although it was thirty years ago that governmental review panels

in the United States and the United Kingdom concluded that the

benzodiazepines shouldn't be prescribed long-term, with dozens of

studies subsequently confirming the wisdom of that advice, the pre¬

scribing of benzodiazepines for continual use goes on. Indeed, a

2005 study of anxious patients in the New England area found that

more than half regularly took a benzodiazepine, and many bipolar

patients now take a benzodiazepine as part of a drug cocktail. 52 The

scientific evidence simply doesn't seem to affect the prescribing

habits of many doctors. "The lesson has either never been learned,

or it has passed people by," Malcolm Lader said. 53

An Episodic Illness Turns Chronic

"With the range of available treatments for

depression, one might wonder why depression-related

disability is on the rise."

— CAROLYN DEWA,

CENTRE FOR ADDICTION AND MENTAL HEALTH,

ONTARIO (2001)

M-Power in Boston is a peer-run advocacy group for the mentally

ill, and while I was at one of their meetings in April 2 008, a young,

quiet woman came up to me and whispered, "I'd be willing to

talk to you." Red hair fell about her shoulders, and she seemed so

shy as to almost be frightened. Yet when Melissa Sances told me

her story a few days later, she spoke in the most candid manner

possible, her shyness transformed into an introspective honesty so

intense that when she was recounting her struggles growing up in

Sandwich on Cape Cod, she suddenly stopped and said: "I was

unhappy, but I didn't have an awareness that I was depressed.” It

was important that I understood the difference between those two

emotions.

Her unhappiness as a child was comprised of familiar ingredi¬

ents. She felt socially awkward and "different" from other kids at

school, and after her parents divorced when she was eight, she and

her brothers lived with their mother, who struggled with depression.

In middle school, Melissa began to come out of her shell, making

friends and feeling "more normal,” only then she ran head-on into

the torments of puberty. "When I was fourteen, I was overweight, I

had acne. I felt like a social outcast, and the kids at high school were

very cruel. I was called a freak and ugly. I would sit at my desk with

AN EPISODIC ILLNESS TURNS CHRONIC

149

my head down, and my hair pulled over my face, trying to hide

from the world. Every day I woke up feeling like I wanted to die."

Today, Melissa is an attractive woman, and so it is a bit surpris¬

ing to learn of this ugly-duckling moment from her past. But with

her schoolmates taunting her, her childhood unhappiness metamor¬

phosed into a deep depression, and when she was sixteen, she tried

to commit suicide by gulping down handfuls of Benadryl and Val¬

ium. She woke up in the hospital, where she was told that she had a

mental illness and was prescribed an antidepressant. "The psychia¬

trist tells me that it adjusts serotonin levels, and that I will probably

have to be on it for the rest of my life. I cried when I heard that."

For a time, Zoloft worked great. "I was like a new person,”

Melissa recalls. "I became open to people, and I made a lot of

friends. I was the pitcher on the softball team.” During her senior

year, she began making plans to attend Emerson College in Boston,

thinking that she would study creative writing. Only then, slowly

but surely, Zoloft's magic started to fade. Melissa began to take

higher doses to keep her depression at bay, and eventually her psy¬

chiatrist switched her to a very high dose of Paxil, which left her

feeling like a zombie. "I was out of it. During a softball game, some¬

one hit a ground ball to me and I just held the ball. I didn't know

what to do with it. I told my team I was sorry."

Melissa has struggled with depression ever since. It followed her

to college, first to Emerson and then to UMass Dartmouth, and al¬

though it did lift somewhat when she became immersed in writing

for the UMass newspaper, it never entirely went away. She tried this

drug and that drug, but none brought any lasting relief. After grad¬

uating, she found a job as an editorial assistant at a magazine, but

depression caught up with her there, too, and in late 2007, the gov¬

ernment deemed her eligible to receive SSDI because of her illness.

"I have always been told that a person has to accept that the ill¬

ness is chronic,” she says, at the end of our interview. "You can be

'in recovery,' but you can never be 'recovered.' But I don't want to

be on disability forever, and I have started to question whether

depression is really a chemical thing. What are the origins of my de¬

spair? How can I really help myself? I want to honor the other parts

of me, other than the sick part that I'm always thinking about.

150

ANATOMY OF AN EPIDEMIC

I think that depression is like a weed that I have been watering,

and I want to pull up that weed, and I am starting to look to people

for solutions. I really don't know what the drugs did for me all these

years, but I do know that I am disappointed in how things have

turned out."

Such is Melissa Sances's story. Today it is a fairly common one. A

distressed teenager is diagnosed with depression and put on an

antidepressant, and years later he or she is still struggling with the

condition. But if we return to the 1950s, we will discover that de¬

pression rarely struck someone as young as Melissa, and it rarely

turned into the chronic suffering that she has experienced. Her

course of illness is, for the most part, unique to our times.

The Way Depression Used to Be

Melancholy, of course, visits nearly everyone now and then. ”1 am a

man, and that is reason enough to be miserable," wrote the Greek

poet Menander in the fourth century B . C ., a sentiment that has been

echoed by writers and philosophers ever since. 2 In his seventeenth-

century tome Anatomy of Melancholy, English physician Robert

Burton advised that everyone "feels the smart of it ... it is most ab¬

surd and ridiculous for any mortal man to look for a perpetual

tenure of happiness in this life.” It was only when such gloomy

states became a "habit,” Burton said, that they became a "dis¬

ease." 3

This was the same distinction that Hippocrates had made more

than two thousand years earlier, when he identified persistent

melancholy as an illness, attributing it to an excess of black bile

(melaina chole in Greek). Symptoms included "sadness, anxiety,

moral dejection, [and] tendency to suicide” accompanied by "pro¬

longed fear." To curb the excess of black bile and bring the four

humors of the body back into balance, Hippocrates recommended

the administration of mandrake and hellebore, changes in diet, and

the use of cathartic and emetic herbs. 4

During the Middle Ages, the deeply melancholic person was seen

AN EPISODIC

LLNESS TURNS CHRONIC

IS 1

as possessed by demons. Priests and exorcists would be called upon

to drive out the devils. With the arrival of the Renaissance in the fif¬

teenth century, the teachings of the Greeks were rediscovered, and

physicians once again offered medical explanations for persistent

melancholy. After William Harvey discovered in 1628 that blood

circulated throughout the body, many European doctors reasoned

that this illness arose from a lack of blood to the brain.

Psychiatry's modern conception of depression has its roots in

Emil Kraepelin's work. In his 1899 book, Lehrbuch der Psychiatrie,

Kraepelin divided psychotic disorders into two broad categories —

dementia praecox and manic-depressive psychosis. The latter cate¬

gory was mostly comprised of three subtypes —depressive episode

only, manic episode only, and episodes of both kinds. But whereas

dementia praecox patients deteriorated over time, the manic-

depressive group had fairly good long-term outcomes. "Usually all

morbid manifestations completely disappear; but where that is

exceptionally not the case, only a rather slight, peculiar psychic

weakness develops,” Kraepelin explained in a 1921 text.'

Today, Kraepelin's depression-only group would be diagnosed

with unipolar depression, and in the 1960s and early 1970s, promin¬

ent psychiatrists at academic medical centers and at the NIMH de¬

scribed this disorder as fairly rare and having a good long-term

course. In her 1968 book, The Epidemiology of Depression, Char¬

lotte Silverman, who directed epidemiology studies for the NIMH,

noted that community surveys in the 1930s and 1940s had found

that fewer than one in a thousand adults suffered an episode of clin¬

ical depression each year. Furthermore, most who were struck did

not need to be hospitalized. In 1955, there were only 7,250 "first

admissions” for depression in state and county mental hospital's.

The total number of depressed patients in the nation's mental hospi¬

tals that year was around 38,200, a disability rate of one in every

4,345 people. 6

Depression, Silverman and others noted, was primarily an "ail¬

ment of middle aged and older persons." In 1956, 90 percent of the

first-admissions to public and private hospitals for depression were

thirty-five years and older. 7 Depressive episodes, explained Balti¬

more psychiatrist Frank Ayd Jr., in his 1962 book, Recognizing the

152

ANATOMY OF AN EPIDEMIC

Depressed Patient, "occur most often after age thirty, have a peak

incidence between age 40 and 60, and taper off sharply thereafter." 8

Although the manic-depressive patients that Kraepelin studied

were severely ill, as their minds were also buffeted by psychotic

symptoms, their long-term outcomes were pretty good. Sixty per¬

cent of Kraepelin's 450 "depressed-only” patients experienced but a

single episode of depression, and only 13 percent had three or more

episodes.’ Other investigators in the first half of the twentieth cen¬

tury reported similar outcomes. In 1931, Horatio Pollock, of the

New York State Department of Mental Hygiene, in a long-term

study of 2,700 depressed patients hospitalized from 1909 to 1920,

reported that more than half of those admitted for a first episode

had but a single attack, and only 17 percent had three or more

episodes. 10 Thomas Rennie, who investigated the fate of 142 de-

pressives admitted to Johns Hopkins Hospital from 1913 to 1916,

determined that 39 percent had "lasting recoveries" of five years or

more.” A Swedish physician, Gunnar Lundquist, followed 216 pa¬

tients treated for depression for eighteen years, and he determined

that 49 percent never experienced a second attack, and that another

21 percent had only one other episode. In total, 76 percent of the

216 patients became "socially healthy" and resumed their usual

work. After a person has recovered from a depressive episode,

Lundquist wrote, he "has the same capacity for work and prospects

of getting on in life as before the onset of the disease." 12

These good outcomes spilled over into the first years of the anti¬

depressant era. In 1972, Samuel Guze and Eli Robins at Washington

University Medical School in St. Louis reviewed the scientific litera¬

ture and determined that in follow-up studies that lasted ten years,

50 percent of people hospitalized for depression had no recurrence

of their illness. Only a small minority of those with unipolar depres¬

sion-one in ten —became chronically ill, Guze and Robins con¬

cluded. 13

That was the scientific evidence that led NIMH officials during

the 1960s and 1970s to speak optimistically about the long-term

course of the illness. "Depression is, on the whole, one of the psy¬

chiatric conditions with the best prognosis for eventual recovery

with or without treatment. Most depressions are self-limited,"

AN EPISODIC ILLNESS TURNS CHRONIC

153

Jonathan Cole wrote in 1964.” "In the treatment of depression,"

explained Nathan Kline that same year, "one always has as an ally

the fact that most depressions terminate in spontaneous remissions.

This means that in many cases regardless of what one does the

patient eventually will begin to get better." 16 George Winokur, a

psychiatrist at Washington University, advised the public in 1969

that "assurance can be given to a patient and to his family that sub¬

sequent episodes of illness after a first mania or even a first depres¬

sion will not tend toward a more chronic course." 16

Indeed, as Dean Schuyler, head of the depression section at the

NIMH explained in a 1974 book, spontaneous recovery rates were

so high, exceeding 50 percent within a few months, that it was diffi¬

cult to "judge the efficacy of a drug, a treatment [electroshock]

or psychotherapy in depressed patients.” Perhaps a drug or electro¬

shock could shorten the time to recovery, as spontaneous remission

often took many months to happen, but it would be difficult for any

treatment to improve on the natural long-term course of depression.

Most depressive episodes, Schuyler explained, "will run their course

and terminate with virtually complete recovery without specific in¬

tervention."”

Short-Term Blues

The history of trials on the short-term efficacy of antidepressants is

a fascinating one, for it reveals much about the capacity of a society

and a medical profession to cling to a belief in the magical merits of

a pill, even though clinical trials produce, for the most part, dispir¬

iting results. The two antidepressants developed in the 1950s, ipro¬

niazid and imipramine, gave birth to two broad types of drugs for

depression, known as monamine oxidase inhibitors (MAOIs) and

tricyclics, and studies in the late 1950s and early 1960s found both

kinds to be wonderfully effective. However, the studies were of du¬

bious quality, and in 1965, the British Medical Council put both

types through a more rigorous test. While the tricyclic (imipramine)

was modestly superior to placebo, the MAOI (phenelzine) was not.

Treatment with this drug was "singularly unsuccessful." 18

154

ANATOMY OF AN EPIDEMIC

Four years later, the NIMH conducted a review of all anti¬

depressant studies, and it found that the "more stringently controlled

the study, the lower the improvement rate reported for a drug." In

well-controlled studies, 61 percent of the drug-treated patients im¬

proved versus 46 percent of the placebo patients, a net benefit of

only 15 percent. "The differences between the effectiveness of anti¬

depressant drugs and placebo are not impressive," it said. 19 The

NIMH then conducted its own trial of imipramine, and it was only

in psychotically depressed patients that this tricyclic showed any

significant benefit over a placebo. Only 40 percent of the drug-

treated patients completed the seven-week study, and the reason so

many dropped out was that their condition "deteriorated.” For

many depressed patients, the NIMH concluded in 1970, "drugs

play a minor role in influencing the clinical course of their illness." 10

The minimal efficacy of imipramine and other antidepressants

led some investigators to wonder whether the placebo response was

the mechanism that was helping people feel better. What the drugs

did, several speculated, was amplify the placebo response, and they

did so because they produced physical side effects, which helped

convince patients that they were getting a "magic pill” for depres¬

sion. To test this hypothesis, investigators conducted at least seven

studies in which they compared a tricyclic to an "active” placebo,

rather than an inert one. (An active placebo is a chemical that pro¬

duces an unpleasant side effect of some kind, like dry mouth.) In six

of the seven, there was no difference in outcomes. 11

That was the efficacy record racked up by tricyclics in the 1970s:

slightly better than inactive placebo, but no better than an active

placebo. The NIMH visited this question of imipramine's efficacy

one more time in the 1980s, comparing it to two forms of psy¬

chotherapy and placebo, and found that nothing had changed. At

the end of sixteen weeks, "there were no significant differences

among treatments, including placebo plus clinical management, for

the less severely depressed and functionally impaired patients.”

Only the severely depressed patients fared better on imipramine

than on a placebo. 21

Societal belief in the efficacy of antidepressants was reborn

with the arrival of Prozac in 1988. Eli Lilly, it seemed, had come up

AN EPISODIC ILLNESS TURNS CHRONIC

155

with a very good pill for the blues. This selective serotonin reuptake

inhibitor (SSRI) was said to make people feel "better than well.”

Unfortunately, once researchers began poking through the clinical

trial data submitted to the FDA for Prozac and the other SSRIs that

were subsequently brought to market, the "wonder drug” story fell

apart.

The first blow to the SSRIs' image came from Arif Khan at the

Northwest Clinical Research Center in Washington. He reviewed

the study data submitted to the FDA for seven SSRIs and con¬

cluded that symptoms were reduced 42 percent in patients treated

with tricyclics, 41 percent in the SSRI group, and 31 percent in

those given a placebo." The new drugs, it turned out, were no

more effective than the old ones. Next, Erick Turner from Oregon

Health and Science University, in a review of FDA data for twelve

antidepressants approved between 1987 and 2004, determined that

thirty-six of the seventy-four trials had failed to show any statisti¬

cal benefit for the antidepressants. There were just as many trials

that had produced negative or "questionable” results as positive

ones. 24 Finally, in 2008, Irving Kirsch, a psychologist at the Univer¬

sity of Hull in the United Kingdom, found that in the trials of

Prozac, Effexor, Serzone, and Paxil, symptoms in the medicated

patients dropped 9.6 points on the Hamilton Rating Scale of

Depression, versus 7.8 points for the placebo group. This was a

difference of only 1.8 points, and the National Institute for Clinical

Excellence in Britain had previously determined that a three-point

drug-placebo difference was needed on the Hamilton scale to

demonstrate a "clinically significant benefit." It was only in a small

subgroup of patients —those most severely depressed —that the

drugs had been shown to be of real use. "Given these data, there

seems little evidence to support the prescription of antidepressant

medication to any but the most severely depressed patients, unless

alternative treatments have failed to provide benefit,” Kirsch and

his collaborators concluded. 25

All of this provoked some soul-searching by psychiatrists in their

journals. Randomized clinical trials, admitted a 2009 editorial in

the British Journal of Psychiatry, had generated "limited valid evi¬

dence” for use of the drugs. 26 A group of European psychiatrists

156

ANATOMY OF AN EPIDEMIC

affiliated with the World Health Organization conducted their own

review of Paxil's clinical data and concluded that "among adults

with moderate to severe major depression," this popular SSRI "was

not superior to placebo in terms of overall treatment effectiveness

and acceptability." 2 ’ Belief in these medications' effectiveness, wrote

Greek psychiatrist John Ioannidis, who has an appointment at Tufts

University School of Medicine in Massachusetts, was a "living

myth." A review of the SSRI clinical data had led to a depressing

end for psychiatry, and, as Ioannidis quipped, he and his colleagues

couldn't even now turn to Prozac and the other SSRIs for relief from

this dispiriting news because, alas, "they probably won't work." 28

There is one other interesting addendum to this research history.

In the late 1980s, many Germans who were depressed turned to Hy¬

pericum perforatum, the plant known as Saint-John's-wort, for re¬

lief. German investigators began conducting double-blind trials of

this herbal remedy, and in 1996, the British Medical Journal sum¬

marized the evidence: In thirteen placebo-controlled trials, 55 per¬

cent of the patients treated with Saint-John's-wort significantly

improved, compared with 22 percent of those given a placebo. The

herbal remedy also bested antidepressants in head-to-head competi¬

tion: In those trials, 66 percent given the herb improved compared

to 55 percent of the drug-treated patients. In Germany, Saint-

John's-wort was effective. But would it work similar magic in Amer¬

icans? In 2001, psychiatrists at eleven medical centers in the United

States reported that it wasn't effective at all. Only 15 percent of the

depressed outpatients treated with the herb improved in their eight-

week trial. Yet —and this was the curious part —only 5 percent of

the placebo patients got better in this study, far below the usual

placebo response. American psychiatrists, it seemed, were not eager

to see anyone as having gotten better, lest the herb prove effective.

But then the NIH funded a second trial of Saint-John's-wort that

had a design that complicated matters for any .researcher who

wanted to play favorites. It compared Saint-John's-wort to both

Zoloft and a placebo. Since the herb causes side effects, such as dry

mouth, it would act at the very least as an active placebo. As such,

this truly was a blinded trial, the psychiatrists unable to rely on side

effects as a clue to which patients were getting what, and here were

AN EPISODIC ILLNESS TURNS CHRONIC

157

the results: Twenty-four percent of the patients treated with Saint-

John's-wort had a "full response,” 25 percent of the Zoloft patients,

and 32 percent of the placebo group. "This study fails to support

the efficacy of H perforatum in moderately severe depression," the

investigators concluded, glossing over the fact that their drug had

failed this test too. 29

The Chronicity Factor, Yet Again

The antidepressants' relative lack of short-term efficacy was not, by

itself, a reason to think that the drugs were causing harm. After all,

most of those treated with antidepressants were seeing their symp¬

toms abate. Medicated patients in the short-term trials were getting

better. The problem was that they were not improving significantly

more than those treated with a placebo. However, during the 1960s,

several European psychiatrists reported that the long-term course of

depression in their drug-treated patients seemed to be worsening.

Exposure to antidepressants, wrote German physician H. P. Ho-

heisel in 1966, appeared to be "shortening the intervals" between

depressive episodes in his patients. These drugs, wrote a Yugosla¬

vian doctor four years later, were causing a "chronification" of the

disease. The tricyclics, agreed Bulgarian psychiatrist Nikola Schip-

kowensky in 1970, were inducing a "change to a more chronic

course.” The problem, it seemed, was that many people treated

with antidepressants were only "partially cured." 50 Their symptoms

didn't entirely remit, and then, when they stopped taking the anti¬

depressant, their depression regularly got much worse again.

With this concern having surfaced in a few European journals, a

Dutch physician, J. D. Van Scheyen, examined the case histories of

ninety-four depressed patients. Some had taken an antidepressant

and some had not, and when Van Scheyen looked at how the two

groups had fared over a five-year period, the difference was star¬

tling: "It was evident, particularly in the female patients, that more

systematic long-term antidepressant medication, with or without

ECT [electroconvulsive therapy], exerts a paradoxical effect on the

158

ANATOMY OF AN EPIDEMIC

recurrent nature of the vital depression. In other words, this thera¬

peutic approach was associated with an increase in recurrent rate

and a decrease in cycle duration. . . . Should [this increase] be re¬

garded as an untoward long-term side effect of treatment with

tricyclic antidepressants?" 31

Over the next twenty years, investigators reported again and

again that people treated with an antidepressant were very likely to

relapse once they stopped taking the drug. In 1973, investigators in

Britain wrote that 50 percent of drug-withdrawn patients relapsed

within six months; 32 a few years later, investigators at the University

of Pennsylvania announced that 69 percent of patients withdrawn

from antidepressants relapsed within this time period. There was,

they confessed, "rapid clinical deterioration in most of the pa¬

tients." 33 In 1984, Robert Prien at the NIMH reported that 71 per¬

cent of depressed patients relapsed within eighteen months of drug

withdrawal. 34 Finally, in 1990, the NIMH added to this gloomy pic¬

ture when it reported the long-term results from its study that had

compared imipramine to two forms of psychotherapy and to a

placebo. At the end of eighteen months, the stay-well rate was best

for the cognitive therapy group (30 percent) and lowest for the

imipramine-exposed group (19 percent). 35

Everywhere, the message was the same: Depressed people who

were treated with an antidepressant and then stopped taking it reg¬

ularly got sick again. In 1997, Ross Baldessarini from Harvard

Medical School, in a meta-analysis of the literature, quantified the

relapse risk: Fifty percent of drug-withdrawn patients relapsed

within fourteen months. 36 Baldessarini also found that the longer a

person was on an antidepressant, the greater the relapse rate fol¬

lowing drug withdrawal. It was as though a person treated with the

drug gradually became less and less able, in a physiological sense, to

do without it. Investigators in Britain came to the same sobering re¬

alization: "After stopping an antidepressant, symptoms tend to

build up gradually and become chronic." 32

AN EPISODIC

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159

Do All Psychotropics Work This Way?

Although a handful of European physicians may have sounded the

alarm about the changing course of depression in the late 1960s and

early 1970s, it wasn't until 1994 that an Italian psychiatrist, Gio¬

vanni Fava, from the University of Bologna, pointedly announced

that it was time for psychiatry to confront this issue. Neuroleptics

had been found to be quite problematic over the long term, the ben¬

zodiazepines had, too, and now it looked like the antidepressants

were producing a similar long-term record. In a 1994 editorial in

Psychotherapy and Psychosomatics, Fava wrote:

Within the field of psychopharmacology, practitioners have

been cautious, if not fearful, of opening a debate on whether

the treatment is more damaging [than helpful].... I wonder

if the time has come for debating and initiating research into

the likelihood that psychotropic drugs actually worsen, at

least in some cases, the progression of the illness which they

are supposed to treat. 38

In this editorial and several more articles that followed, Fava of¬

fered a biological explanation for what was going on with the anti¬

depressants. Like antipsychotics and benzodiazepines, these drugs

perturb neurotransmitter systems in the brain. This leads to com¬

pensatory "processes that oppose the initial acute effects of a

drug. . . . When drug treatment ends, these processes may operate

unopposed, resulting in appearance of withdrawal symptoms and

increased vulnerability to relapse,” he wrote. 35 Moreover, Fava

noted, pointing to Baldessarini's findings, it was evident that the

longer one stayed on antidepressants, the worse the problem.

"Whether one treats a depressed patient for three months, or three

years, it does not matter when one stops the drugs. A statistical

trend suggested that the longer the drug treatment, the higher the

likelihood of relapse." 40

But, Fava also wondered, what was the outcome for people who

stayed on antidepressants indefinitely? Weren't they also relapsing

I6o • ANATOMY OF AN EPIDEMIC

with great frequency? Perhaps the drugs cause "irreversible receptor

modifications," Fava said, and, as such, "sensitize” the brain to de¬

pression. This could explain the "bleak long term outcome of

depression." He summed up the problem in this way:

Antidepressant drugs in depression might be beneficial in the

short term, but worsen the progression of the disease in

the long term, by increasing the biochemical vulnerability to

depression. . . . Use of antidepressant drugs may propel the

illness to a more malignant and treatment unresponsive

course. 41

This possibility was now front and center in psychiatry. "His

question and the several related matters . . . are not pleasant to

contemplate and may seem paradoxical, but they now require open-

minded and serious clinical and research consideration,” Baldessarini

said. 42 Three physicians from the University of Louisville School of

Medicine echoed the sentiment. "Long-term antidepressant use may

be depressogenic,” they wrote, in a 1998 letter to the Journal of

Clinical Psychiatry. "It is possible that antidepressant agents modify

the hardwiring of neuronal synapses [which] not only render anti¬

depressants ineffective but also induce a resident, refractory depres¬

sive state." 43

It's the Disease, Not the Drug

Once again, psychiatry had reached a moment of crisis. The specter

of supersensitivity psychosis had stirred up a hornets' nest in the

early 1980s, and now, in the mid-1990s, a concern very similar in

kind had appeared. This time, the stakes were perhaps even higher.

Fava was raising this issue even as U.S. sales of SSRIs were soaring.

Prominent psychiatrists at the best medical schools in the United

States had told newspaper and magazine reporters of their wonders.

These drugs were now being prescribed to an ever-larger group of

people, including to more than a million American children. Could

AN EPISODIC ILLNESS TURNS CHRONIC

• 161

the field now confess that these medications might be making peo¬

ple chronically depressed? That they led to a "malignant" long-term

course? That they caused biological changes in the brain that "sen¬

sitized” a person to depression? And if that were so, how could they

possibly be prescribed to young children and teenagers? Why would

doctors do that to children? This concern of Fava's needed to be

hushed up, and hushed up fast. Early in 1994, after Fava first

broached the subject, Donald Klein from Columbia University told

Psychiatric News that this subject was not going to be investigated.

"The industry is not interested [in this question], the NIMF1 is

not interested, and the FDA is not interested," he said. "Nobody is

interested." 44

Indeed, by this time, leaders of American psychiatry were already

coming up with an alternative explanation for the "bleak" long¬

term outcomes, one that spared their drugs any blame. The old epi¬

demiological studies from the pre-antidepressant era, which had

shown that people regularly recovered from a severe depressive

episode and that a majority then stayed well, were "flawed.” A

panel of experts convened by the NIMH put it this way: "Improved

approaches to the description and classification of [mood] disorders

and new epidemiologic studies [have] demonstrated the recurrent

and chronic nature of these illnesses, and the extent to which they

represent a continual source of distress and dysfunction for affected

individuals." 45 Depression was at last being understood, that was

the story that psychiatry embraced, and textbooks were rewritten to

tell of this advance in knowledge. Not long ago, noted the 1999 edi¬

tion of the American Psychiatric Association's Textbook of Psychia¬

try, it was believed that "most patients would eventually recover

from a major depressive episode. However, more extensive studies

have disproved this assumption." 45 It was now known, the APA said,

that "depression is a highly recurrent and pernicious disorder.”

Depression, it seemed, had never been the relatively benign illness

described by Silverman and others at the NIMH in the late 1960s

and early 1970s. And with depression reconceived in this way, as a

chronic illness, psychiatry now had a rationale for long-term use

of antidepressants. The problem wasn't that exposure to an

antidepressant caused a biological change that made people more

162.

ANATOMY OF AN EPIDEMIC

vulnerable to depression; the problem was that once the drug was

withdrawn, the disease returned. Moreover, psychiatry did have

studies proving the merits of keeping people on antidepressants.

After all, relapse rates were higher for patients withdrawn from

the medications than for those maintained on the drugs. "Anti¬

depressants reduce the risk of relapse in depressive disorder, and

continued treatment with antidepressants would benefit many pa¬

tients with recurrent depressive disorder,” explained a group of

psychiatrists who reviewed this literature. 47

During the 1990s, psychiatrists in the United States and else¬

where fleshed out the spectrum of outcomes achieved with this new

paradigm of care, which emphasized "maintaining” people on the

medications. One-third of all unipolar patients, researchers con¬

cluded, are "non-responders” to antidepressants. Their symptoms

do not abate over the short term, and this group is said to have

a poor long-term outcome. Another third of unipolar patients

are "partial responders" to antidepressants, and in short-term trials,

they show up as being helped by the drugs. The problem, NIMH in¬

vestigators discovered, in a long-term study called the Collaborative

Program on the Psychobiology of Depression, was that these drug-

maintained patients fared poorly over the long term. "Resolution of

major depressive episode with residual subthreshold depressive

symptoms, even the first lifetime episode, appears to be the first step

of a more severe, relapsing, and chronic future course,” explained

Lewis Judd, a former director of the NIMH, in a 2000 report. 4 ' The

final third of patients see their symptoms remit over the short term,

but only about half of this group, when maintained on an antide¬

pressant, stay well for long periods of time. 49

In short, two-thirds of patients initially treated with an antide¬

pressant can expect to have recurrent bouts of depression, and only

a small percentage of people can be expected to recover and stay

well. "Only 15% of people with unipolar depression experience a

single bout of the illness," the APA's 1999 textbook noted, and for

the remaining 85 percent, with each new episode, remissions be¬

come "less complete and new recurrences develop with less provo¬

cation." 50 This outcomes data definitely told of a pernicious

disorder, but then John Rush, a prominent psychiatrist at Texas

AN EPISODIC

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• 163

Southwestern Medical Center in Dallas, suggested that "real-world

outcomes" were even worse. Those outcome statistics arose from

clinical trials that had cherry-picked patients most likely to respond

well to an antidepressant, he said. "Longer-term clinical outcomes

of representative outpatients with nonpsychotic major depressive

disorder treated in daily practice in either the private or public sec¬

tors are yet to be well defined." 51

In 2004, Rush and his colleagues filled in this gap in the medical

literature. They treated 118 "real world” patients with antidepres¬

sants and provided them with a wealth of emotional and clinical

support "specifically designed to maximize clinical outcomes." This

was the best care that modern psychiatry could provide, and here

were their real-world results: Only 26 percent of the patients even

responded to the antidepressant (meaning that their symptoms de¬

creased at least 50 percent on a rating scale), and only about half of

those who responded stayed better for any length of time. Most

startling of all, only 6 percent of the patients saw their depression

fully remit and stay away during the yearlong trial. These "findings

reveal remarkably low response and remission rates," Rush said. 52

This dismal picture of real-world outcomes was soon confirmed

by a large NIMH study known as the STAR*D trial, which Rush

helped direct. Most of the 4,041 real-world outpatients enrolled in

the trial were only moderately ill, and yet fewer than 20 percent re¬

mitted and stayed well for a year. "Most individuals with major de¬

pressive disorders have a chronic course, often with considerable

symptomatology and disability even between episodes,” the investi¬

gators concluded. 53

In the short span of forty years, depression had been utterly

transformed. Prior to the arrival of the drugs, it had been a fairly

rare disorder, and outcomes generally were good. Patients and their

families could be reassured that it was unlikely that the emotional

problem would turn chronic. It just took time —six to twelve

months or so —for the patient to recover. Today, the NIMH informs

the public that depressive disorders afflict one in ten Americans

every year, that depression is "appearing earlier in life” than it did

in the past, and that the long-term outlook for those it strikes is

glum. "An episode of major depression may occur only once in a

164

ANATOMY OF AN EPIDEMIC

person's lifetime, but more often, it recurs throughout a person's

life," the NIMH warns. 54

Unmedicated v. Medicated Depression

We've now arrived at an intellectual place similar to what we expe¬

rienced with the antipsychotics: Can it really be that antidepres¬

sants, which are so popular with the public, worsen long-term

outcomes? All of the data we've reviewed so far indicates that the

drugs do just that, but there is one piece of evidence that we are

still missing: What does unmedicated depression look like today?

Does it run a better long-term course? Unfortunately, as researchers

from the University of Ottawa discovered in 2008, there aren't

good-quality randomized trials comparing long-term outcomes in

antidepressant-treated and never-medicated patients. As such, they

concluded, randomized trials "provide no guidance for longer treat¬

ment." 55 However, we can search for "naturalistic" studies that

might help us answer this question.' 1 '

Researchers in the UK, the Netherlands, and Canada investigated

this question by looking back at case histories of depressed patients

whose medication use had been tracked. In a 1997 study of out¬

comes at a large inner-city facility, British scientists reported that

ninety-five never-medicated patients saw their symptoms decrease

by 62 percent in six months, whereas the fifty-three drug-treated pa¬

tients experienced only a 33 percent reduction in symptoms. The

medicated patients, they concluded, "continued to have depressive

symptoms throughout the six months." 56 Dutch investigators, in a

retrospective study of the ten-year outcomes of 222 people who had

* The caveat with the naturalistic studies is that the unmedicated cohort, at the

moment of initial diagnosis, may not be as depressed as those who go on drugs.

Furthermore, those who eschew drugs may also have a greater "inner re¬

silience." Even given these caveats, we should be able to gain a sense of the

course of unmedicated depression from the naturalistic studies, and see how it

compares to the course of depression treated with antidepressants.

AN EPISODIC

LLNESS TURNS CHRONIC

165

suffered a first episode of depression, found that 76 percent of those

not treated with an antidepressant recovered and never relapsed,

compared to 50 percent of those prescribed an antidepressant. 57

Finally, Scott Patten, from the University of Calgary, plumbed a

large Canadian health database to assess the five-year outcomes of

9,508 depressed patients, and he determined that the medicated pa¬

tients were depressed on average nineteen weeks each year, versus

eleven weeks for those not taking the drugs. These findings, Patten

wrote, were consistent with Giovanni Fava's hypothesis that "anti¬

depressant treatment may lead to a deterioration in the long-term

course of mood disorders." 58

A study conducted by the World Health Organization in fifteen

cities around the world to assess the value of screening for depres¬

sion led to similar results. The researchers looked for depression in

patients who showed up at health clinics for other complaints, and

then, in a fly-on-the-wall manner, followed those they had identified

as depressed for the next twelve months. They reasoned that the

general practitioners in the clinics would detect depression in some

of the patients but not all, and hypothesized that outcomes would

fall into four groups: those diagnosed and treated with antidepres¬

sants would fare the best, those diagnosed and treated with benzo¬

diazepines would fare the second best, those diagnosed and treated

without psychotropics the third best, and those undetected and un¬

treated the worst. Alas, the results were the opposite. Altogether,

the WHO investigators identified 740 people as depressed, and it

was the 484 who weren't exposed to psychotropic medications

(whether diagnosed or not) that had the best outcomes. They en¬

joyed much better "general health" at the end of one year, their de¬

pressive symptoms were much milder, and a lower percentage were

judged to still be "mentally ill." The group that suffered most from

"continued depression" were the patients treated with an antide¬

pressant. The "study does not support the view that failure to

recognize depression has serious adverse consequences," the investi¬

gators wrote. 59

Next, researchers in Canada and the United States studied

whether antidepressant use affected disability rates. In Canada,

Carolyn Dewa and her colleagues at the Centre for Addiction and

166

ANATOMY OF AN EPIDEMIC

One-Year Outcomes in WHO Screening Study for Depression

The WHO investigators reported that a higher percentage ofthe unmedicated group recovered,

and th at "conti n u i n g depression" was highest in those treated with an antidepressant. Source:

Goldberg, D.'The effects of detection and treatment of major depression in primary care." British

Journal of General Practice 48 (1 998): 1840-44.

Mental Health in Ontario identified 1,281 people who went on

short-term disability between 1996 and 1998 because they missed

ten consecutive days of work due to depression. The 564 people

who subsequently didn't fill a prescription for an antidepressant re¬

turned to work, on average, in 77 days, while the medicated group

took 105 days to get back on the job. More important, only 9 per¬

cent of the unmedicated group went on to long-term disability, com¬

pared to 19 percent of those who took an antidepressant. 51 * "Does

the lack of antidepressant use reflect a resistance to adopting a sick

role and consequently a more rapid return to work?" Dewa won-

* This study powerfully illustrates why we, as a society, may be deluded about

the merits of antidepressants. Seventy-three percent of those who took an anti¬

depressant returned to work (another 8 percent quit or retired), and undoubt¬

edly many in that group would tell of how the drug treatment helped them.

They would become societal voices attesting to the benefits of this paradigm of

care, and without a study of this kind, there would be no way to know that the

medications were, in fact, increasing the risk of long-term disability.

AN EPISODIC

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• 167

The Risk of Disability for Depressed Patients

0% 20% 40% 60% 80% 100%

This was a study of 1,281 employees in Canada who went on short-term disability due to

depression. Those who took an antidepressant were more than twice as likely to go on to long¬

term disability. Source: Dewa, C "Pattern of antidepressant use and duration of depression-

related absence from work." British Journal of Psychiatry 1 83 (2003): 507-1 3.

dered. 60 In a similar vein. University of Iowa psychiatrist William

Coryell and his NIMH-funded colleagues studied the six-year

"naturalistic" outcomes of 547 people who suffered a bout of de¬

pression, and they found those who were treated for the illness were

three times more likely than the untreated group to suffer a "cessa¬

tion" of their "principal social role” and nearly seven times more

likely to become "incapacitated.” Moreover, while many of the

treated patients saw their economic status markedly decline during

the six years, only 17 percent of the unmedicated group saw their

incomes drop, and 59 percent saw their incomes rise. "The un¬

treated individuals described here had milder and shorter-lived ill¬

nesses [than those who were treated], and, despite the absence of

treatment, did not show significant changes in socioeconomic status

in the long term," Coryell wrote. 61

Several countries also observed that following the arrival of the

SSRIs, the number of their citizens disabled by depression dramati¬

cally increased. In Britain, the "number of days of incapacity" due

to depression and neurotic disorders jumped from 38 million in

1984 to 117 million in 1999, a threefold increase. 62 Iceland re¬

ported that the percentage of its population disabled by depression

168 •

ANATOMY OF AN EPIDEMIC

NIMH's Study of Untreated Depression

In this study, the NIMH investigated the naturalistic outcomes of people diagnosed with major

depression who got treatment and those who did not. At the end of six years, the treated patients

were much more likely to have stopped functioning in their usual societal roles and to have

become incapacitated. Source: Coryell, W. "Characteristics and significance of untreated major

depressive disorder." American Journal of Psychiatry 152 (1995): 1124-29.

nearly doubled from 1976 to 2000. If antidepressants were truly

helpful, the Iceland investigators reasoned, then the use of these

drugs "might have been expected to have a public health impact

by reducing disability, morbidity, and mortality due to depressive

disorders." 63 In the United States, the percentage of working-age

Americans who said in health surveys that they were disabled by de¬

pression tripled during the 1990s.“

There is one final study we need to review. In 2006, Michael

Posternak, a psychiatrist at Brown University, confessed that "un¬

fortunately, we have little direct knowledge regarding the untreated

course of major depression." The poor long-term outcomes detailed

in APA textbooks and the NIMH studies told the story of medicated

depression, which might be a very different beast.,To study what

untreated depression might be like in modern times, Posternak and

his collaborators identified eighty-four patients enrolled in the

NIMH's Psychobiology of Depression program who, after recover¬

ing from an initial bout of depression, subsequently relapsed but did

not then go back on medication. Although these patients were not a

AN EPISODIC

LLNESS TURNS CHRONIC

• 169

"never-exposed” group, Posternak could still track their "un¬

treated” recovery from this second episode of depression. Here

were the results: Twenty-three percent recovered in one month, 67

percent in six months, and 85 percent within a year. Kraepelin,

Posternak noted, had said that untreated depressive episodes usu¬

ally cleared up within six to eight months, and these results pro¬

vided "perhaps the most methodologically rigorous confirmation of

this estimate." 65

The old epidemiological studies were apparently not so flawed

after all. This study also showed why six-week trials of the drugs

had led psychiatry astray. Although only 23 percent of the unmedi¬

cated patients were recovered after one month, spontaneous remis¬

sions continued after that at the rate of about 2 percent per week,

and thus at the end of six months, two-thirds were depression free.

It takes time for unmedicated depression to lift, and that is missed in

short-term trials. "If as many as 85% of depressed individuals who

go without somatic treatment spontaneously recover within one

year, it would be extremely difficult for any intervention to demon¬

strate a superior result to this," Posternak said. 66

It was just as Joseph Zubin had warned in 1955: "It would be

foolhardy to claim a definite advantage for a specified therapy with¬

out a two- to five-year follow-up." 67

Nine Million and Counting

We can now see how the antidepressant story all fits together, and

why the widespread use of these drugs would contribute to a rise in

the number of disabled mentally ill in the United States. Over the

short term, those who take an antidepressant will likely see their

symptoms lessen. They will see this as proof that the drugs work, as

will their doctors. However, this short-term amelioration of symp¬

toms is not markedly greater than what is seen in patients treated

with a placebo, and this initial use also puts them onto a problem¬

atic long-term course. If they stop taking the medication, they are at

high risk of relapsing. But if they stay on the drugs, they will also

1 7 0 •

ANATOMY OF AN EPIDEMIC

likely suffer recurrent episodes of depression, and this chronicity in¬

creases the risk that they will become disabled. The SSRIs, to a

certain extent, act like a trap in the same way that neuroleptics do.

We can also track the rise in the number of people disabled by de¬

pression during the antidepressant era. In 1955, there were 38,200

people in the nation's mental hospitals due to depression, a per-

capita disability rate of 1 in 4,345. Today, major depressive disorder

is the leading cause of disability in the United States for people ages

fifteen to forty-four. According to the NIMH, it affects 15 million

American adults, and researchers at Johns Hopkins School of Public

Health reported in 2008 that 58 percent of this group is "severely

impaired." 68 That means nearly nine million adults are now dis¬

abled, to some extent, by this condition.

It's also important to note that this disability doesn't arise solely

from the fact that people treated with antidepressants are at high

risk of suffering recurrent episodes of depression. SSRIs also cause a

multitude of troubling side effects. These include sexual dysfunc¬

tion, suppression of REM sleep, muscle tics, fatigue, emotional

blunting, and apathy. In addition, investigators have reported that

long-term use is associated with memory impairment, problem¬

solving difficulties, loss of creativity, and learning deficiencies. "Our

field," confessed Maurizio Fava and others at Massachusetts

General Hospital in 2006, "has not paid sufficient attention to the

presence of cognitive symptoms emerging or persisting during long¬

term antidepressant treatment. . . . These symptoms appear to be

quite common." 69

Animal studies have also produced alarming results. Rats fed

high doses of SSRIs for four days ended up with neurons that were

swollen and twisted like corkscrews. "We don't know if the cells are

dying,” the researchers from Jefferson Medical College in Philadel¬

phia wrote. "These effects may be transient and reversible. Or they

may be permanent." 70 Other reports have suggested.that the drugs

may reduce the density of synaptic connections in the brain, cause

cell death in the hippocampus, shrink the thalamus, and trigger ab¬

normalities in frontal-lobe function. None of these possibilities has

been well studied or documented, but something is clearly going

AN EPISODIC ILLNESS TURNS CHRONIC

171

amiss if symptoms of cognitive impairment in long-term users of

antidepressants are "quite common."

Melissa

I interviewed a number of people who receive SSI or SSDI due to de¬

pression, and many told stories similar to Melissa Sances's. They

first took an antidepressant when they were in their teens or early

twenties, and the drug worked for a time. But then their depression

returned, and they have struggled with depressive episodes ever

since. Their stories fit to a remarkable degree with the long-term

chronicity detailed in the scientific literature. I also caught up with

Melissa a second time, nine months after our first interview, and her

struggles remained much the same. In the fall of 2008, she started

taking a high dose of a monoamine oxidase inhibitor, which pro¬

vided a few weeks of relief, and then her depression returned with a

vengeance. She was now considering electroshock therapy, and as

we ate lunch at a Thai restaurant, she spoke, in a wistful manner, of

how she wished her treatment could have been different.

"I do wonder what might have happened if [at age sixteen] I

could have just talked to someone, and they could have helped me

learn about what I could do on my own to be a healthy person. I

never had a role model for that. They could have helped me with

my eating problems, and my diet and exercise, and helped me learn

how to take care of myself. Instead, it was you have this problem

with your neurotransmitters, and so here, take this pill Zoloft, and

when that didn't work, it was take this pill Prozac, and when that

didn't work, it was take this pill Effexor, and then when I started

having trouble sleeping, it was take this sleeping pill," she says, her

voice sounding more wistful than ever. "I am so tired of the pills."

The Bipolar Boom

"I would like to point out that in the history of

medicine, there are many examples of situations

where the vast majority of physicians did something

that turned out to be wrong. The best example is

bloodletting, which was the most common medical

practice from the first century A.D. until the

nineteenth century."

— NASSIR GHAEMI, TUFTS MEDICAL CENTER,

APA CONFERENCE (2008)

At the American Psychiatric Association's 2008 annual meeting in

Washington, D.C., there were press conferences each day, and dur¬

ing the presentations that told of the great advances that lay ahead,

the leaders of the APA regularly urged the reporters and science

writers in attendance to help "get out the message that [psychiatric]

treatment works and is effective, and that our diseases are real dis¬

eases just like cardiovascular diseases and cancer," said APA presi¬

dent Carolyn Robinowitz. "We need to work together as partners

so we can get the word out to patients and families." The press had

an important role to play, explained incoming president Nada

Logan Stotland, because "the public is vulnerable to misinforma¬

tion." She urged the reporters to "help us inform the public that

psychiatric illnesses are real, psychiatric treatments work, and that

our data is as solid as in other areas of medicine.”

I scribbled all of these quotes in my notebook, even though it

didn't seem that Anatomy of an Epidemic was going to quite fit the

partnership model that the APA had in mind, and then each day I

would go for a stroll in the great exhibit hall, which I always en¬

joyed. Eli Lilly, Pfizer, Bristol-Myers Squibb, and the other leading

vendors of psychiatric drugs all had huge welcoming centers, where,

THE BIPOLAR BOOM

• 173

if you were a doctor, you could collect various trinkets and gifts.

Pfizer's seemed to be the most popular, as the psychiatrists could

pick up a new personalized gift each day, their names printed on a

mini-flashlight one day and a mobile phone charger the next. They

could also win a gift by playing a video game called the Physician's

Race Challenge, the pace of their virtual self racing toward the fin¬

ish line governed by how well they answered questions about the

wonders of Geodon as a treatment for bipolar illness. After playing

that game, many lined up to have their photo taken and stamped on

a campaign button that said: "Best Doctor on Earth."

The best-attended events of the conference were the industry-

sponsored symposiums. At every breakfast, lunch, and dinner hour,

the doctors could enjoy a sumptuous free meal, which was then

followed by talks on the chosen topic. There were symposiums on

depression, ADHD, schizophrenia, and the prescribing of antipsy-

chotics to children and adolescents, and nearly all of the speakers

hailed from top academic schools. The fact that they all were being

paid by the drug companies was openly acknowledged, as the APA,

as part of a new disclosure policy, had published a chart listing all

the ways that pharmaceutical money flowed to these "thought lead¬

ers.” In addition to receiving research monies, most of the "experts"

served as consultants, on "advisory boards,” and as members of

"speakers' bureaus.” Thus, you could see that Joseph Biederman, a

psychiatrist at Massachusetts General Hospital in Boston who, dur¬

ing the 1990s, led the way in popularizing juvenile bipolar disorder,

received research grants from eight firms, acted as a "consultant" to

nine, and served as a "speaker” for eight. His long list of pharma¬

ceutical clients was not all that unusual, and at times, speakers had

to update their information in the disclosure guide when they strode

to the podium, as they had recently added yet another pharmaceuti¬

cal company to their list of clients. After Harvard Medical School's

Jean Frazier dutifully relayed such information, at a symposium de¬

voted to the merits of putting children on multiple psychiatric drugs,

she said, without any apparent hint of irony, "I hope you find my

presentation unbiased.”

The speakers put on very polished presentations, evidence of

the training in public speaking they had received from the

1 7 4 •

ANATOMY OF AN EPIDEMIC

pharmaceutical firms. They regularly opened with a joke before

moving on to their PowerPoint slides, which were splashed on ball¬

room screens larger than those found in most theaters. Often the

diners were given handheld remote devices to answer multiple-

choice questions during the presentations, with dramatic music

playing as they keyed in their responses, much as it might during

"Final Jeopardy," and when their collective wisdom was splashed

on the screens, most usually got the answer right. "You guys are so

smart,” one speaker said.

Patty Duke provided the 2008 APA meeting with its celebrity pa¬

tient story. AstraZeneca sponsored her talk, and the company

spokesman who introduced her, apparently worried that somehow

the audience might miss the point of what she had to say, informed

everyone that "the take-home message is that mental illness is diag-

nosable and recognizable, and that treatment works." Then the

Oscar-winning actress, clad in a pumpkin orange dress, told of

how she had suffered from undiagnosed bipolar illness for twenty

years, during which time she drank excessively and was sexually

promiscuous. Diagnosis and medication "made me marriage mate¬

rial," she said, and whenever she speaks to patient groups around

the country, she hammers this point home. "I tell them, 'Take your

medicines!' " she said. The drugs fix the disease "with very little

downside!" The audience clapped loudly at that, and then America's

favorite identical cousin offered the psychiatrists a final benediction:

"We are beyond blessed to have people like you who have chosen to

take care of us and to lead us to a balanced life. ... I get my infor¬

mation from you and NAMI [National Alliance on Mental Illness],

and if I resisted such information, I would deserve to have a net

thrown over me. When I hear someone say, at one of my talks, 'I

don't need the medication, I don't take it,' I tell them to 'sit down,

you are making a fool of yourself.'

That led to a standing ovation, and so, as I put away my note¬

book, it seemed certain that this was a meeting where the bottom-

line message, no matter where you went, would be quite well

controlled. Nearly everything was set up and organized in a way

that told of a profession quite confident in its therapeutics, and

while I knew that Martin Harrow would be giving a talk on his

THE BIPOLAR BOOM

175

long-term study of schizophrenia outcomes, he had been allotted

only twenty minutes, and his session had been assigned to one of the

convention center's smallest rooms. His presentation would be the

one exception to the rule, and so I didn't expect to hear anything

startling on the Tuesday afternoon that I squeezed my way into a

crowded, slightly larger room for a forum titled "Antidepressants in

Bipolar Disorder." I figured that the speakers would simply present

trial results that justified, in one way or another, the use of these

drugs, but soon I was writing furiously away. The discussion, which

was led by the top bipolar experts in the country, including the two

grand old men of biological psychiatry in the United States, Freder¬

ick Goodwin and Robert Post, focused on this question: Do anti¬

depressants worsen the long-term course of bipolar disorder? And

notably so?

"The illness has been altered," said Goodwin, who in 1990 coau¬

thored the first edition of his text Manic-Depressive Illness, which is

considered the bible in the field. Today "we have a lot more rapid

cycling than we described in the first edition, a lot more mixed

states than we described in the first edition, a lot more lithium re¬

sistance, and a lot more lithium treatment failure than there was in

the first edition. The illness is not what Kraepelin described any¬

more, and the biggest factor, I think, is that most patients who have

the illness get an antidepressant before they ever get exposed to a

mood stabilizer."

This was the opening salvo in what turned into an hour-long con¬

fessional. Although not all the speakers agreed that antidepressants

had been disastrous for bipolar patients, that was the general

theme, and nobody questioned Goodwin's bottom-line summary

that bipolar outcomes had noticeably worsened in the past twenty

years. Antidepressants, said Nassir Ghaemi, from Tufts Medical

Center, can cause manic switches and turn patients into "rapid

cyclers,” and may increase the amount of time they spend in depres¬

sive episodes. Rapid cycling, Post added, led to a very bad end.

"The number of episodes, and it's a very rich literature [docu¬

menting this], is associated with more cognitive deficits," he said.

"We are building more episodes, more treatment resistance, more

cognitive dysfunction, and there is data showing that if you have

1 7 6 •

ANATOMY OF AN EPIDEMIC

four depressive episodes, unipolar or bipolar, it doubles your late-

life risk of dementia. And guess what? That isn't even the half of

it. . . . In the United States, people with depression, bipolar, and

schizophrenia are losing twelve to twenty years in life expectancy

compared to people not in the mental health system.”

These were words that told of a paradigm of care that had

completely failed, of treatment that made patients constantly sympto¬

matic and cognitively impaired, and led to their early death as well.

"Now you just heard that one of the things we do doesn't work very

well in the long term," Post practically screamed. "So what the hell

should we be doing?"

The confessions came fast and furious. Psychiatry, of course, had

its "evidence base” for using antidepressants in bipolar disorder,

but, Post said, the clinical trials conducted by pharmaceutical com¬

panies "are virtually useless for us as clinicians. . . . They don't tell

us what we really need to know, what our patients are going to re¬

spond to, and if they don't respond to that first treatment, what

should be the next iteration, and how long they should stay on

things." Only a small percentage of people, he added, actually "re¬

spond to these crummy treatments, like antidepressants." As for

recent pharma-funded trials that had shown that bipolar patients

withdrawn from antipsychotic medications relapsed at high rates,

which theoretically served as evidence that patients needed to take

these drugs long-term, those studies "were designed to get relapse

[in the placebo group]," Goodwin said. "It isn't evidence that the

drug is still needed; it's evidence that if you suddenly change a brain

that has adapted to the drug, you are going to get relapse.” Added

Post: "Right now, fifty years after the advent of antidepressant

drugs, we still don't really know how to treat bipolar depression.

We need new treatment algorithms that aren't just made up.”

This was all much like the moment in The Wizard of Oz when

the curtain is pulled back and the mighty wizard is revealed as a

frail old man. For anyone in the audience who had spent his or her

morning in Pfizer’s welcoming center, answering video-game ques¬

tions about the wonders of Geodon for bipolar illness, it must have

been crushing. Thirty years earlier, Guy Chouinard and Barry Jones

had rattled the profession with their talks on drug-induced

THE BIPOLAR BOOM

• 177

"supersensitivity psychosis," and now the profession was being

asked to confront the fact that bipolar outcomes were worse today

than they had been thirty years earlier, and that antidepressants

were a likely culprit. Stimulants, it seemed, could make bipolar

patients worse too, and at last Ghaemi told the audience that psy¬

chiatry needed to adopt a "Hippocratic” approach to the use of

psychiatric medications, which would require them to stop prescrib¬

ing them unless they had good evidence they were truly beneficial

over the long term. "Diagnosis, not druggery," he said, and at one

point, several in the audience —which had grown increasingly agi¬

tated by this discussion —booed him.

"Can fifty thousand psychiatrists be wrong?" he asked, speaking

about the profession's use of antidepressants as a treatment for

bipolar disorder. "I think that the answer is yes, probably."

Bipolar Before Lithium

Readers of this book, having come this far in the text, cannot be

surprised to learn that outcomes for bipolar disorder have dramatic¬

ally worsened in the pharmacotherapy era. The only surprising

thing is that this failure was so openly discussed at the APA meeting.

Given what the scientific literature revealed about the long-term

outcomes of medicated schizophrenia, anxiety, and depression, it

stood to reason that the drug cocktails used to treat bipolar illness

were not going to produce good long-term results. The increased

chronicity, the functional decline, the cognitive impairment, and the

physical illness —all of these can be expected to show up in people

treated with a cocktail that often includes an antidepressant, an an¬

tipsychotic, a mood stabilizer, a benzodiazepine, and perhaps a

stimulant, too. This was a medical train wreck that could have been

anticipated, and unfortunately, as we trace the history of this story,

the details will seem all too familiar.

Although "bipolar” illness is a diagnosis of recent origin, first

showing up in the APA's Diagnostic and Statistical Manual in 1980

(DSM-III), medical texts dating back to Hippocrates contain

178 •

ANATOMY OF AN EPIDEMIC

descriptions of patients suffering from alternating episodes of mania

and melancholia. "Melancholia,” wrote German physician Chris¬

tian Vater in the seventeenth century, "often passes into mania and

vice versa. The melancholies now laugh, now are saddened, now ex¬

press numberless other absurd gestures and forms of behaviour.”

The English mad doctor John Haslam told of how "the most furi¬

ous maniacs suddenly sink into a profound melancholy, and the

most depressed and miserable objects become violent and raving.”

In 1854, a French asylum doctor, Jules Baillarger, dubbed this illness

la folk a double forme. It was an uncommon, but recognizable form

of insanity. 1

When Emil Kraepelin published his diagnostic texts, he put these

patients into his manic-depressive group. This diagnostic category

also included patients who suffered from depression or mania only

(as opposed to both), and Kraepelin reasoned that these varied emo¬

tional states all arose from the same underlying disease. The split¬

ting of manic-depressive disorder into separate unipolar and bipolar

factions got its start in 1957, when a German psychiatrist, Karl

Leonhard, determined that the manic form of the illness seemed to

run more in families than the depressive form did. He called the

manic patients "bipolar,” and other researchers then identified addi¬

tional differences between the unipolar and bipolar forms of manic-

depressive illness. Onset occurred earlier in bipolar patients, often

when they were in their twenties, and it also appeared that bipolar

patients were at somewhat higher risk of becoming chronically ill.

In his 1969 book, Manic Depressive Illness, George Winokur at

Washington University in St. Louis treated unipolar depression and

bipolar illness as separate entities, and with this distinction having

been made, he and others began reviewing the literature on manic-

depressive illness to isolate the data on the "bipolar" patients. On av¬

erage, in the older studies, about one-fourth of the manic-depressive

group had suffered from manic episodes and thus were "bipolar." By

all accounts, this was a rare disorder. There were perhaps 12,750

people hospitalized with bipolar illness in 1955, a disability rate of

one in every 13,000 people. 2 That year there were only about 2,400

"first admissions” for bipolar illness in the country's mental

hospitals. 3

THE BIPOLAR BOOM

• 179

As Winokur discovered, the long-term outcomes of the manic pa¬

tients in the pre-drug era had been pretty good. In his 1931 study,

Horatio Pollock reported that 50 percent of the patients admitted to

New York State mental hospitals for a first attack of mania never

suffered a second attack (during an eleven-year follow-up), and only

20 percent experienced three or more episodes. 1 F. I. Wertham, from

Johns Hopkins Medical School, in a 1929 study of two thousand

manic-depressive patients, determined that 80 percent of the manic

group recovered within a year, and that fewer than 1 percent re¬

quired long-term hospitalization. 5 In Gunnar Lundquist's study, 75

percent of the 103 manic patients recovered within ten months, and

during the following twenty years, half of the patients never had an¬

other attack, and only 8 percent developed a chronic course. Eighty-

five percent of the group "socially recovered” and resumed their

former positions. 6 Finally, Ming Tsuang, at the University of Iowa,

studied how eighty-six manic patients admitted to a psychiatric hos¬

pital between 1935 and 1944 fared over the next thirty years, and he

found that nearly 70 percent had good outcomes, which meant they

married, lived in their own homes, and worked. Half were asympto¬

matic during this lengthy follow-up. All in all, the manic patients

had fared as well as the unipolar patients in Tsuang's study. 7

These results, Winokur wrote, revealed that there "was no basis

to consider that manic depressive psychosis permanently affected

those who suffered from it. In this way it is, of course, different

from schizophrenia." While some people suffered multiple episodes

of mania and depression, each episode was usually only "a few

months in duration," and "in a significant number of patients, only

one episode of illness occurs." Most important of all, once patients

recovered from their bipolar episodes, they usually had "no diffi¬

culty resuming their usual occupations." 8

Gateways to Bipolar

Today, according to the NIMH, bipolar illness affects one in every

forty adults in the United States, and so, before we review the

l8o

ANATOMY OF AN EPIDEMIC

outcomes literature for this disorder, we need to try to understand

this astonishing increase in its prevalence.’ Although the quick-and-

easy explanation is that psychiatry has greatly expanded the diag¬

nostic boundaries, that is only part of the story. Psychotropic

drugs —both legal and illegal —have helped fuel the bipolar boom.

In studies of first-episode bipolar patients, investigators at

McLean Hospital, the University of Pittsburgh, and the University

of Cincinnati Hospital found that at least one-third had used mari¬

juana or some other illegal drug prior to their first manic or psy¬

chotic episode. 10 This substance abuse, the University of Cincinnati

investigators concluded, may "initiate progressively more severe af¬

fective responses, culminating in manic or depressive episodes, that

then become self-perpetuating.” 11 Even the one-third figure may be

low; in 2008, researchers at Mt. Sinai Medical School reported that

nearly two-thirds of the bipolar patients hospitalized at Silver Hill

Hospital in Connecticut in 2005 and 2006 experienced their first

bout of "mood instability" after they had abused illicit drugs. 12

Stimulants, cocaine, marijuana, and hallucinogens were common

culprits. In 2007, Dutch investigators reported that marijuana use

"is associated with a fivefold increase in the risk of a first diagnosis

of bipolar disorder" and that one-third of new bipolar cases in the

Netherlands resulted from it. 13

Antidepressants have also led many people into the bipolar

camp, and to understand why, all we have to do is return to the dis¬

covery of this class of drugs. We see tuberculosis patients treated

with iproniazid dancing in the wards, and while that magazine re¬

port was probably a bit exaggerated, it told of lethargic patients

suddenly behaving in a manic way. In 1956, George Crane pub¬

lished the first report of antidepressant-induced mania, and this

problem has remained present in the scientific literature ever since. 14

In 1985, Swiss investigators tracking changes in the patient mix at

Burgholzli psychiatric hospital in Zurich reported that the percent¬

age with manic symptoms jumped dramatically following the intro¬

duction of antidepressants. "Bipolar disorders increased; more

patients were admitted with frequent episodes,” they wrote. 15 In a

1993 practice guide to depression, the APA confessed that "all anti¬

depressant treatments, including ECT [electroconvulsive therapy],

THE BIPOLAR BOOM

• 181

may provoke manic or hypomanic episodes." 16 A few years later, re¬

searchers at Yale University School of Medicine quantified this risk.

They reviewed the records of 87,290 patients diagnosed with de¬

pression or anxiety between 1997 and 2001 and determined those

treated with antidepressants converted to bipolar at the rate of 7.7

percent per year, which was three times greater than for those not

exposed to the drugs. 17 As a result, over longer periods, 20 to 40

percent of all patients initially diagnosed with unipolar depression

today eventually convert to bipolar illness.” Indeed, in a recent sur¬

vey of members of the Depressive and Manic-Depressive Associa¬

tion, 60 percent of those with a bipolar diagnosis said they had

initially fallen ill with major depression and had turned bipolar

after exposure to an antidepressant. 19

This is data that tells of a process that routinely manufactures

bipolar patients. "If you create iatrogenically a bipolar patient,” ex¬

plained Fred Goodwin, in a 2005 interview in Primary Psychiatry,

"that patient is likely to have recurrences of bipolar illness even if

the offending antidepressant is discontinued. The evidence shows

that once a patient has had a manic episode, he or she is more likely

to have another one, even without the antidepressant stimula¬

tion." 20 Italy's Giovanni Fava put it this way: "Antidepressant-

induced mania is not simply a temporary and fully reversible

phenomenon, but may trigger complex biochemical mechanisms of

illness deterioration." 21

With illegal and legal drugs greasing the road to bipolar illness, it

is little wonder that a rare disorder in 1955 has become common¬

place today. SSRIs took the country by storm in the 1990s, and

from 1996 to 2004, the number of adults diagnosed with bipolar ill¬

ness rose 56 percent. At the same time, psychiatry's steady expan¬

sion of diagnostic boundaries over the past thirty-five years has

helped fuel the bipolar boom too.

When bipolar disorder was first separated from manic-depressive

illness, the diagnosis required a person to have suffered bouts of

mania and depression so severe that each type had resulted in hos¬

pitalization. Then, in 1976, Goodwin and others at the NIMH

suggested that if a person had been hospitalized for depression but

not for mania, and yet had experienced a mild episode of mania

1 8 2 •

ANATOMY OF AN EPIDEMIC

(hypomania), he or she could be diagnosed with bipolar II, a less

severe form of the disease. Then the bipolar II diagnosis was ex¬

panded so that it included people who had never been hospitalized

for either depression or mania, but simply had experienced episodes

of both. Next, in the 1990s, the psychiatric community decided that

a diagnosis of hypomania no longer required four days of "elevated,

expansive, or irritable mood,” but rather simply two days of such

moodiness. Bipolar illness was on the march, and with the diagnos¬

tic boundaries expanded in this way, researchers were suddenly an¬

nouncing that it affected up to 5 percent of the population. But even

that didn't end the bipolar boom: In 2003, former NIMH director

Lewis Judd and others argued that many people suffer "subthresh¬

old” symptoms of depression and mania, and thus could be diag¬

nosed with "bipolar spectrum disorder."” There was now bipolar I,

bipolar II, and a "bipolarity intermediate between bipolar disorder

and normality," one bipolar expert explained. 23 Judd calculated

that 6.4 percent of American adults suffer from bipolar symptoms;

others have argued that one in every four adults now falls into the

catchall bipolar bin, this once-rare illness apparently striking almost

as frequently as the common cold. 24

The Lithium Years

With the psychopharmacology revolution in full bloom during the

1960s, it seemed that every major psychiatric disorder should have

its own magic bullet, and once bipolar disorder was separated from

manic-depressive illness, psychiatry found a suitable candidate in

lithium. Salts made from this alkali metal had been hanging around

the fringes of medicine for more than 150 years, and then suddenly,

during the early 1970s, lithium was touted as a cure'of sorts for this

newly identified disease. "I have not found another treatment in

psychiatry that works so quickly, so specifically, and so permanently

as lithium for recurrent manic and depressive mood states," said

Columbia University psychiatrist Ronald Fieve, in his 1975 book,

Moodswing . 25

THE BIPOLAR BOOM

183

Nature's lightest metal, lithium was discovered in 1818, found in

rocks off the Swedish coast. It was reported to dissolve uric acid and

thus was marketed as a therapy that could break up kidney stones

and the uric crystals that gathered in the joints of people who suf¬

fered from gout. In the late 1800s and early 1900s, lithium became

a popular ingredient in elixirs and tonics, and it would even be

added to beers and other beverages. However, lithium was eventu¬

ally found to have no uric-acid-dissolving properties, and in 1949,

the FDA banned it after it was found to cause cardiovascular prob¬

lems. 26

Its revival as a psychiatric drug began in Australia, where the

physician John Cade fed it to guinea pigs and observed that it made

them docile. In 1949, he reported that he had successfully treated

ten manic patients with lithium; however, he neglected to mention

in his published article that the treatment killed one person and

made two others severely ill. As makers of lithium tonics had long

known, lithium can be toxic even in fairly small doses. Both intel¬

lectual function and motor movement may become impaired, and if

too high of a dose is given, a person may lapse into a coma and die.

As a group, psychiatrists in the United States showed little inter¬

est in lithium until bipolar made its appearance as a distinct illness.

Prior to that time, Thorazine and other neuroleptics were used to

curb manic episodes and thus there was no need for another drug

that seemed to have similar brain-dampening effects. But once

George Winokur published his book in 1969 dividing manic-

depressive illness into unipolar and bipolar forms, psychiatry had a

new disease in need of its own antidote.

Since no pharmaceutical company could patent lithium, the APA

took the lead in getting the FDA to approve it. Only a few placebo-

controlled trials of the drug were ever conducted. In 1985, UK re¬

searchers who scoured the scientific literature could only find four

of any merit. However, in those studies, lithium produced a good re¬

sponse in 75 percent of the patients, which was much higher than

the response rate in the placebo group. 27 The second part of the ev¬

idence base for lithium came, as usual, from withdrawal studies. In¬

vestigators who analyzed nineteen such trials in 1994 found that

53.5 percent of the patients withdrawn from lithium relapsed,

184

ANATOMY OF AN EPIDEMIC

versus 37.5 percent of the lithium-maintained patients. That was

taken as evidence that lithium prevented relapse, although the re¬

searchers noted that in the few studies where patients had been

gradually withdrawn from the drug, only 29 percent relapsed

(which was lower than the rate among the drug-maintained pa¬

tients). 28

All in all, this was not particularly robust evidence that lithium

benefited patients, and during the 1980s, several investigators began

raising concerns about its long-term effects. They noted that re¬

admission rates for mania in both the United States and the United

Kingdom had risen since lithium was introduced, and eventually it

became clear why bipolar patients were turning up at hospital emer¬

gency rooms with such great frequency.

Various studies found that more than 50 percent of lithium-

treated patients would quit taking the drug in fairly short order,

usually because they objected to how the drug dulled their minds

and slowed their physical movements, and when they did, they re¬

lapsed at astonishingly high rates. In 1999, Ross Baldessarini

reported that half of all patients relapsed within five months of quit¬

ting lithium, even though in the absence of exposure to the drug, it

took nearly three years for 50 percent of bipolar patients to relapse.

The time between episodes following lithium withdrawal was seven

times shorter than it was naturally. 29 "The risk of recurrence after

discontinuation of lithium therapy . . . especially of mania, is much

higher than predicted by a patient's course before treatment or

by general knowledge of the natural history of the illness,"

Baldessarini wrote. 30 Other investigators noted the same phenome¬

non: "Manic relapse is readily triggered [by lithium withdrawal],

probably by the release of supersensitized receptors or membrane

pathways," explained Jonathan Himmelhoch from the University of

Pittsburgh. 31

This meant that bipolar patients who were treated with lithium

and then stopped taking it ended up "worse than if they had never

had any drug treatment," wrote UK psychiatrist Joanna Mon-

crieff. 32 A Scottish psychiatrist, Guy Goodwin, concluded in 1993

that if patients were exposed to lithium and then quit taking it

within the first two years, the risk of relapse was so great that the

THE BIPOLAR BOOM

185

drug may be "harmful to bipolar patients." The higher hospitaliza¬

tion readmission rates for bipolar patients since the introduction of

lithium "could be explained entirely” by this drug-induced worsen¬

ing, he said. 33

Yet the patients who stayed on lithium weren't faring particularly

well either. Roughly 40 percent relapsed within two years of their

initial hospitalization, and by the end of five years, more than 60

percent fell sick again. 31 There was a core group of good, long-term

lithium responders —perhaps 20 percent of those initially treated

with the drug —but for the majority of patients, it provided little

long-term relief. In 1996, Martin Harrow and Joseph Goldberg,

from the University of Illinois, reported that at the end of 4.5 years,

41 percent of the patients on lithium had "poor outcomes," nearly

one-half had been rehospitalized, and as a group they weren't

"functioning” any better than those not taking the drug. 35 This was

a dismal finding, and then Michael Gitlin at UCLA reported similar

five-year results for his lithium-treated bipolar patients. "Even ag¬

gressive pharmacological maintenance treatment does not prevent

relatively poor outcome in a significant number of bipolar pa¬

tients,” he wrote. 36

Although lithium is still in use today, it lost its place as a first-line

therapy once "mood stabilizers" were brought to the market in the

late 1990s. As Moncrieff wrote in 1997, summing up lithium's

record of efficacy: "There are indications that it is ineffective in the

long-term outlook of bipolar disorders, and it is known to be associ¬

ated with various forms of harm." 37

Bipolar All the Time

There are really two narratives to be dug out of the scientific litera¬

ture regarding the treatment of bipolar illness with psychiatric

drugs. The first tells of lithium's rise and fall as a magic bullet for

the disorder. The second tells of how bipolar outcomes have dra¬

matically worsened during the psychopharmacology era, with

experts in the field documenting this at every turn.

l86

ANATOMY OF AN EPIDEMIC

As early as 1965, before lithium had made its triumphant entry

into American psychiatry, German psychiatrists were puzzling over

the change they were seeing in their manic-depressive patients.

Patients treated with antidepressants were relapsing frequently, the

drugs "transforming the illness from an episodic course with free in¬

tervals to a chronic course with continuous illness," they wrote. The

German physicians also noted that in some patients, "the drugs

produced a destabilization in which, for the first time, hypomania

was followed by continual cycling between hypomania and depres¬

sion." 38

This was obviously alarming, for the good outcomes in manic-

depressive patients arose from the fact that they spent a large part of

their lives in symptom-free intervals between episodes, during

which time they functioned well. Antidepressants were destroying

those asymptomatic interludes, or at least dramatically shortening

them. Prior to the drug era, Kraepelin and others reported that only

about one-third of manic patients suffered three or more episodes in

their lives. Yet studies of bipolar patients in the 1960s and 1970s

told of two-thirds who were becoming chronically ill. "The admin¬

istration of tricyclics may account for artificially high relapse rate

estimates," Fred Goodwin wrote in 1979. "Induction of mania,

breakdown of otherwise long episodes into multiple ones . . . induc¬

tion of rapid cycling . . . are some of the mechanisms by which the

administration of tricyclics may contribute to an increase in the

number of episodes." 39

Once again, it was becoming apparent that psychiatric medica¬

tions were worsening the course of a mental illness. In 1983,

Athanasious Koukopoulos, director of a mood disorders clinic in

Rome, said that he and his colleagues were observing the same thing

in their Italian patients. "The general impression of clinicians today

is that the course of recurrences of manic-depressive illness has

substantially changed in the last 20 years," he wrote. "The recur¬

rences of many patients have become more frequent. One sees more

manias and hypomanias . . . more rapid cyclers, and more chronic

depressions." Whereas in the pre-drug era rapid cyclers were un¬

known, 16 percent of Koukopoulos's manic-depressive patients were

now in this predicament, and they were suffering an astonishing 6.5

THE BIPOLAR BOOM

187

mood episodes annually, up from less than one episode a year prior

to being treated with an antidepressant. "It certainly seems para¬

doxical,” he admitted, "that a treatment that is therapeutic for

depression can worsen the further course of the disease." 40

In spite of such information, antidepressants continued to be pre¬

scribed to bipolar patients, and even today, 60 to 80 percent are

exposed to an SSRI or some other antidepressant. As a result, inves¬

tigators have continued to document the harm done. In 2000,

Nassir Ghaemi reported that in a study of thirty-eight bipolar pa¬

tients treated with an antidepressant, 55 percent developed mania

(or hypomania) and 23 percent turned into rapid cyclers. This

antidepressant-treated group also spent "significantly more time de¬

pressed" than a second group of bipolar patients who weren't ex¬

posed to this class of medication. 41 "There are significant risks of

mania and long-term worsening with antidepressants," Ghaemi

wrote a few years later, repeating a message that had been uttered

many times before. 42 At the University of Louisville, Rif El-Mallakh

similarly concluded that antidepressants may "destabilize the ill¬

ness, leading to an increase in the number of both manic and de¬

pressive episodes." The drugs, he added, "increase the likelihood of

a mixed state," in which feelings of depression and mania occur si¬

multaneously. 43

In 2003, Koukopoulos chimed in again, reporting that anti-

depressant-induced rapid cycling fully abates in only one-third of

patients over the long term (even after the offending antidepressant

is withdrawn), and that 40 percent of patients continue to "cycle rap¬

idly with unmodified severity" for years on end. 14 Soon, in 2005, El-

Mallakh pointed out yet another problem: Antidepressants could

induce a "chronic, dysphoric, irritable state” in bipolar patients,

meaning that they were almost continually depressed and miser¬

able. 45 Finally, in 2008, in a large NIMH study called the

Systematic Treatment Enhancement Program for Bipolar Disorder

(STEP-BD), "the major predictor of worse outcome was antidepres¬

sant use, which about 60 percent of patients received,” Ghaemi

noted. 46 The antidepressant users were nearly four times more likely

than the non-exposed patients to develop rapid cycling, and twice

as likely to have multiple manic or depressive episodes. 42 "This

188 •

ANATOMY OF AN EPIDEMIC

study," wrote Ghaemi, in an editorial that appeared in the Amer¬

ican journal of Psychiatry, "may be one more nail in the coffin of

antidepressant use in bipolar disorder."

During the past ten years, several large studies have documented

just how constantly symptomatic bipolar patients are today. In a

long-term follow-up of 146 bipolar I patients who enrolled in an

NIMH study in 1978-81, Lewis Judd found that they were de¬

pressed 32 percent of the time, manic or hypomanic 9 percent of the

time, and suffering from mixed symptoms 6 percent of the time. 48

The bipolar II patients in that study arguably fared even worse:

They were depressed 50 percent of the time. "The nature of this de¬

ceptively 'milder' form of manic-depressive illness is so chronic as to

seem to fill the entire life," Judd wrote. 45 Russell Joffe, at the New

Jersey Medical School, reported in 2004 that 33 percent of the bipo¬

lar I patients and 22 percent of the bipolar II patients he studied

were rapid cyclers, and both groups were symptomatic nearly half

of the time. 50 Meanwhile, Robert Post announced that nearly two-

thirds of the 258 bipolar patients he studied had four or more

episodes per year. 51

All of these studies showed the same bottom-line result: "It is

now well established that bipolar disorders are chronic, with a

course characterized by frequent affective episode recurrence," Judd

said. 52

The Harm Done

In a 2 000 paper published in the Psychiatric Quarterly, a Harvard

Medical School psychiatrist, Carlos Zarate, and a psychiatrist who

worked for Eli Lilly, Mauricio Tohen, opened up a new line of con¬

cern: Bipolar patients today aren't just much more symptomatic

than in the past, they also don't function as well. "In the era prior to

pharmacotherapy, poor outcome in mania was considered a rela¬

tively rare occurrence,” Zarate and Tohen wrote. "However, mod¬

ern outcome studies have found that a majority of bipolar patients

THE BIPOLAR BOOM

• 189

evidence high rates of functional impairment." What, they won¬

dered, could explain "these differences"? 53

The remarkable decline in the functional outcomes of bipolar pa¬

tients is easy to document. In the pre-lithium era, 85 percent of

mania patients would return to work or to their "pre-morbid" so¬

cial role (as a housewife, for example). As Winokur wrote in 1969,

most patients had "no difficulty resuming their usual occupations."

But then bipolar patients began cycling through emergency rooms

more frequently, employment rates began to decline, and soon in¬

vestigators were reporting that fewer than half of all bipolar pa¬

tients were employed or otherwise "functionally recovered.” In

1995, Michael Gitlin at UCLA reported that only 28 percent of his

bipolar patients had a "good occupational outcome” at the end of

five years. 54 Three years later, psychiatrists at the University of

Cincinnati announced that only 24 percent of their bipolar patients

were "functionally recovered” at the end of one year. 55 David

Kupfer at the University of Pittsburgh School of Medicine, in a

study of 2,839 bipolar patients, discovered that even though 60 per¬

cent had attended college and 30 percent had graduated, two-thirds

were unemployed. 56 "In summary," wrote Ross Baldessarini in a

2007 review article, "functional status is far more impaired in type

I bipolar patients than previously believed, [and] remarkably, there

is some evidence that functional outcome in type II bipolar patients

may be even worse than in type I." 57

The antidepressants, by increasing the frequency of episodes

that bipolar patients suffer, naturally reduce their ability to return

to work. But, as has become evident in recent years, the problem

runs much deeper than that. One of the hallmarks of manic-

depressive illness, dating back to Kraepelin, was that once people

recovered from their episodes of mania and depression, they were

as smart as they had been before they became ill. As Zarate and

Tohen noted in their 2000 paper, "studies conducted prior to 1975

found no consistent findings in cognitive deficits in bipolar

patients.” But lithium was known to slow thinking, and suddenly

researchers began reassessing this belief. In 1993, NIMH investiga¬

tors compared cognitive function in bipolar and schizophrenia

igo • ANATOMY OF AN EPIDEMIC

patients, and they concluded that while the bipolar patients

showed signs of impairment, the deficits were "more severe and

extensive in schizophrenia." 5 '

This was something of a glass-half-full finding. You could inter¬

pret it to mean that cognitive impairment was not that bad in

bipolar patients, or, if you remembered the pre-lithium days, you

might wonder why these patients were suddenly showing signs of

mental decline. But this was just the beginning salvo of a tragic

story. Once lithium monotherapy fell from favor, psychiatrists

began to turn to "drug cocktails" to treat their patients, and soon

investigators had this to report: "Cognitive impairments [that] exist

in schizophrenia and affective disorders . . . cannot be qualitatively

distinguished with sufficient reliability." 59 The degree of impairment

in these two illnesses was suddenly converging, and in 2 001, Faith

Dickerson at the Sheppard Pratt Health System in Baltimore pro¬

vided a more detailed picture of that convergence. She ran seventy-

four medicated schizophrenia patients and twenty-six medicated

bipolar patients through a series of tests that assessed forty-one cog¬

nitive and social-functioning variables, and found that the bipolar

patients were as impaired as the schizophrenia patients on thirty-six

of the forty-one measures. There was "a similar pattern of cognitive

functioning in patients with bipolar disorder as compared to those

with schizophrenia," she wrote. "On most measures of social func¬

tioning, our patients with bipolar disorder were not significantly

different from those in the schizophrenia group." 60

After that, reports of significant cognitive decline in bipolar

patients seemed to pour in from psychiatric researchers around

the globe —English, Swedish, German, Australian, and Spanish in¬

vestigators all told of it. The Australians reported in 2007 that even

when bipolar patients are only mildly symptomatic, they are

"neuropsychological scarred” —impaired in their decision-making

skills, their verbal fluency, and their ability to remember things. 61

Meanwhile, Spanish investigators, after noting that cognitive func¬

tion in their bipolar and schizophrenia patients "did not differ over

time in any test,” concluded that both groups suffered from dys¬

function in the "prefrontal cortex and temporolimbic structures."

They also observed that "the more medications the patients re-

THE BIPOLAR BOOM • lgi

ceived, the greater the psychosocial functioning impairment." 62 * Fi¬

nally, English researchers who looked at the daily lives of bipolar

patients found that more than two-thirds "rarely or never engaged

in social activities with friends,” their social lives nearly as impover¬

ished as those diagnosed with schizophrenia. 63

This was an astonishing convergence in long-term outcomes be¬

tween the two diagnostic groups, and while the psychiatrists in the

United States and abroad who documented it mostly tried, in their

discussion of the phenomenon, to ignore the medication elephant in

the room, several did confess that it was possible that psychiatric

drugs were to blame. Conventional antipsychotics, said Zarate in

one of his papers, "may have a negative impact on the overall

course of the illness." 64 Later, he and Tohen wrote that "medication

induced changes may be yet another factor in explaining the dis¬

crepancies in recovery rates between earlier and more recent stud¬

ies." The antidepressants, they noted, might cause a "worsening of

the course of illness,” while the antipsychotics might lead to more

"depressive episodes” and "lower functional recovery rates." Cog¬

nitive impairment was a primary reason that medicated schizophre¬

nia patients fared so poorly over the long term, they said, and "it

has been suggested that drug side effects may in part explain the

cognitive deficits in bipolar disorder patients." 65 Baldessarini, in his

2007 review, also acknowledged that "neuropharmacological-neuro-

toxic factors” might be causing "cognitive deficits in bipolar dis¬

order patients.” Finally, Kupfer threw one more concern into the

mix. He detailed all the physical illnesses that now struck bipolar

patients —cardiovascular problems, diabetes, obesity, thyroid dys¬

function, etc. —and wondered whether "treatment factors such as

toxicity from medications” could be causing these devastating ail¬

ments, or at least contributing to them. 66

All of these writers put their concerns into a conditional context,

* In this study, the investigators reported that cognitive impairment, from least

to most, was as follows, according to drug treatment received: lithium

monotherapy, untreated, neuroleptic monotherapy, and then combination drug

therapy. However, no details are given about the "untreated” group and

whether they had previous exposure to psychiatric medications.

192.

ANATOMY OF AN EPIDEMIC

stating that the drugs might be causing this mental and physical

deterioration in their patients. But it's easy to see that their hesi¬

tancy was scientifically unwarranted. Schizophrenia and manic-

depressive illness had been diagnostically born as distinct in kind

precisely because those with schizophrenia deteriorated cognitively

over time, into dementia, while the manic-depressive group did

not/' The convergence in outcomes developed once both groups

were treated with similar drug cocktails (which usually included an

antipsychotic). "The field is witnessing a convergence of pharmaco¬

logical approaches to the treatment of schizophrenia and bipolar

disorder," wrote Stephen Stahl, author of Antipsychotics and Mood

Stabilizers, in 2005. It was adopting "similar blended treatments for

these two disease states."” Psychiatric drugs, of course, perturb var¬

ious neurotransmitter pathways in the brain, and thus once schizo¬

phrenia and bipolar patients are on similar drug cocktails, they

suffer from similar abnormalities in brain function. The conver¬

gence of outcomes in the two groups reflects an iatrogenic process

at work: The two groups, apart from whatever "natural" problems

they may have, both end up suffering from what could be dubbed

"polypharmacy psychiatric drug illness.”

Today, bipolar illness is a far cry from what it once was. Prior to

the psychopharmacology era, it had been a rare disorder, affecting

perhaps one in ten thousand people. Now it affects one in forty (or

by some counts, one in twenty). And even though most patients

today —at initial diagnosis —are not nearly as ill as the hospitalized

patients of the past, their long-term outcomes are almost incompre¬

hensibly worse. In his 2007 review, Baldessarini even detailed, step

by step, this remarkable deterioration in outcomes. In the pre-drug

* The schizophrenia patients who routinely deteriorated into dementia were

Kraepelin's dementia praecox patients. That group of patients presented with

symptoms very different in kind from schizophrenia patients today, and as we

saw in Martin Harrow’s fifteen-year study, many unmedicated schizophrenia

patients recover. Courtenay Harding reported the same thing in her long-term

study —many of the unmedicated patients had completely recovered. So it's un¬

clear what percentage of people diagnosed with schizophrenia today, if not

continually medicated, would deteriorate cognitively over time.

THE BIPOLAR BOOM

193

The Transformation of Bipolar Disorder in the Modern Era

Pre-Lithium Bipolar

Medicated Bipolar Today

Prevalence

1 in 5,000 to 20,000

1 in 20 to 50

Good long-term

functional outcomes

7 5 % to 9 0%

3 3%

Symptom course

Time-limited acute episodes of

mania and major depression with

recovery to euthymia and a fav¬

orable functional adaptation

between episodes

Slow or incomplete recovery

from acute episodes, con¬

tinued risk of recurrences,

and sustained morbidity over

time

Cognitive function

No impairment between epi¬

sodes or long-term impairment

Impairment even between

episodes; long-term impair¬

ment in many cognitive

domains; impairment is

similar to what is observed in

medicated schizophrenia

This information is drawn from multiple sources. See in particular Huxley, N. "Disability and its

treatment in bipolar disorder patients." Bipolar Disorders 9 (2007): 18S-96.

era, there was "recovery to euthymia [no symptoms] and a favor¬

able functional adaptation between episodes." Now there is "slow

or incomplete recovery from acute episodes, continued risk of

recurrences, and sustained morbidity over time.” Before, 85 percent

of bipolar patients would regain complete "premorbid” functioning

and return to work. Now only a third achieve "full social and occu¬

pational functional recovery to their own premorbid levels." Before,

patients didn't show cognitive impairment over the long term. Now

they end up nearly as impaired as those with schizophrenia. This all

tells of an astonishing medical disaster, and then Baldessarini

penned what might be considered a fitting epitaph for the entire

psychopharmacology revolution:

Prognosis for bipolar disorder was once considered relatively

favorable, but contemporary findings suggest that disability

and poor outcomes are prevalent, despite major therapeutic

advances. 68

194

ANATOMY OF AN EPIDEMIC

The Graphic That Tells It All

We are now coming to the close of our examination of the outcomes

literature for the major psychiatric disorders (for adults), and a re¬

turn to Martin Harrow’s fifteen-year study on schizophrenia out¬

comes brings it to a climactic end. In addition to following

schizophrenia patients, Harrow studied a group of eighty-one pa¬

tients with "other psychotic disorders” that would have been

described by Kraepelin as a manic-depressive cohort. There were

thirty-seven bipolar and twenty-eight unipolar patients in this group,

and the remaining sixteen had various milder psychotic disorders.

Nearly half of this group stopped taking psychiatric medications

during the study, and thus Harrow really had four groups he

followed: schizophrenia patients on and off meds and manic-

depressive patients on and off meds. Before we review the results,

we can run a quick check of our own thoughts: How should we ex¬

pect the long-term outcomes of all four groups to stack up?

Go ahead —take out a pencil and jot down what you believe the

results will be.

Here are his findings. Over the long term, the manic-depressive

patients who stopped taking psychiatric drugs fared pretty well. But

their recovery took time. At the end of two years, they were still

struggling with their illness. Then they began to improve, and by the

end of the study their collective scores fell into the "recovered” cat¬

egory (a score of one or two on Harrow's global assessment scale).

The recovered patients were working at least part-time, they had

"acceptable" social functioning, and they were largely asympto¬

matic. Their outcomes fit with Kraepelin's understanding of manic-

depressive illness.

The manic-depressive patients who stayed on their psychiatric

medications did not fare so well. At the end of two years, they re¬

mained quite ill, so much so they were now a little bit worse than

the schizophrenia patients off meds. Then, over the next two-and-

one-half years, while the manic-depressive and schizophrenia pa¬

tients who were off meds improved, the manic-depressive patients

who kept taking their pills did not, such that by the end of 4.5

THE BIPOLAR BOOM

195

years, they were doing markedly worse than the schizophrenia off-

med group. That disparity remained through the rest of the study,

and thus here is how the long-term outcomes stacked up, from best

to worst: manic-depressive off meds, schizophrenia off meds,

manic-depressive on meds, and then schizophrenia on meds. 69

Schizophrenia, of course, has long been the psychiatric diagnosis

with the worst long-term prognosis. It is the most severe mental ill¬

ness that nature has to offer. But in this NIMH-funded study, two

groups of medicated patients fared worse than the unmedicated

schizophrenia patients. The results tell of a medical treatment gone

horribly awry, and yet they do not come as a surprise. Anyone who

knew the history of the outcomes literature in psychiatry, a history

that began to unfold more than fifty years ago, could have predicted

that the outcomes would stack up in this way.

In terms of contributing to our modern-day epidemic of disabling

mental illness, the bipolar numbers are staggering. In 1955, there

were about 12,750 people hospitalized with bipolar illness. Today,

according to the NIMH, there are nearly six million adults in the

15-Year Outcomes for Schizophrenia and Manic-Depressive Patients

Worst

outcomes

Follow-up Follow-up Follow-up Follow-up Follow-up

In this graphic, the group labeled "manic depressive" consisted of psychotic patients with bipolar

illness, unipolar depression, and milder psychotic disorders. Source: Harrow, M. "Factors involved

in outcome and recovery in schizophrenia patients not on antipsychotic medications." The Journal

of Nervous and Mental Disease, 195 (2 007): 406-14.

19 6

ANATOMY OF AN EPIDEMIC

United States with this diagnosis, and according to researchers at

the Johns Hopkins School of Public Health, 83 percent are "se¬

verely impaired” in some facet of their lives. 7 " Bipolar illness is now

said to be the sixth leading cause of medical-related disability in the

world, right behind schizophrenia, and in the near future, as more

and more people are diagnosed with this condition and put on drug

cocktails, we can expect that bipolar will climb past schizophrenia

and take its place behind major depression as the mental illness that

fells the most people in the United States. Such is the fruit, bitter in

kind, born from the psychopharmacology revolution.

Bipolar Narratives

I interviewed more than sixty people with psychiatric diagnoses for

this book, and roughly half at some point had been diagnosed as

bipolar. Yet of the thirty or so who got that diagnosis, only four suf¬

fered from what might be called "organic” bipolar illness, and that

is to say they were hospitalized for a manic episode and had no

prior exposure to illicit drugs or antidepressants. Now that we

know what science has to tell us about the modern bipolar boom,

we can revisit the stories of three people we met in Chapter 2, and

see how their stories fit into that story of science. Then we can hear

from two people diagnosed with bipolar who, if they had been

enrolled in Harrow's fifteen-year study, would have fallen into his

"off-meds" group.

Dorea Vierling-Clausen

If we look at Dorea Vierling-Clausen's story now, we can see that

she has good reason to believe that she should never have been di¬

agnosed with bipolar illness. She went to see a therapist in Denver

because she cried too much. She had no history of mania. But then

she was prescribed an antidepressant and starting having trouble

sleeping, and soon she had a bipolar diagnosis and a prescription

for a drug cocktail that included an antipsychotic. A bright teenager

THE BIPOLAR BOOM

197

had been turned into a mental patient, and Dorea would have con¬

tinued to be one for the rest of her life if she had not weaned herself

from the drugs. When I last spoke to her, in the spring of 2009, she

was aglow with the blush of motherhood, as she had recently given

birth to a son, Reuben. She and Angela were busily raising their

children, with Dorea planning shortly to resume her postdoctoral

research at Massachusetts General Hospital, the memory of her

"bipolar" days receding into an ever-more-distant past.

Monica Briggs

During the time that I worked on this book, Monica Briggs was the

one person who, after an initial interview, got off SSDI (or SSI). She

secured a full-time position with the Transformation Center, a peer-

run organization in Boston that focuses on helping people "re¬

cover" from mental illness, and if you parse her medical story, it's

easy to see that her return to work was related to a change in her

medication.

When we first met, I mentioned to Monica the risk of

antidepressant-induced mania, and as she remembered back to her

breakdown at Middlebury College, a light went on: "I got manic

within six weeks of being put on desipramine," she said. "I'm sure

that's what happened to me.” After that initial manic episode, she

was prescribed a drug cocktail that included an antidepressant, and

she spent the next twenty years cycling in and out of hospitals,

struggling constantly with depression, manic episodes, and suicidal

impulses. Psychiatrists put her on eight or nine different antidepres¬

sants, and she also went through a series of electroshock treatments.

None of this worked. Then, in 2006, she "casually" stopped taking

an antidepressant. For the first time, she was on lithium alone, and

bingo —the suicidal feelings went away, as did the depression and

mania. That symptom relief is what enabled her to work full-time,

and now, as she looks back on the horrible twenty years, she is

stunned by what she sees: "I have not yet recovered from the

immensity of the likelihood that my roulette game with antidepres¬

sants exacerbated my illness."

198

ANATOMY OF AN EPIDEMIC

Steve happen

Steve Lappen, who is a leader of the Depressive and Bipolar Support

Alliance in Boston, was diagnosed with manic-depressive illness in

1969, when he was nineteen years old. He was one of the four peo¬

ple I interviewed whose manic-depressive illness was "organic” in

kind, and on the first day we met, he was in something of a hyper

state, talking so fast that I quickly put my pen away and took out a

tape recorder instead. "OK,” I told him, "fire away."

Raised in Newton, Massachusetts, in a family he describes as

dysfunctional, Steve got tagged with the "bad apple" label early in

life, both by his teachers at school and his parents at home. "I was

disruptive in class,” he says. "Every day, during the pledge of alle¬

giance to the flag, I would go sharpen my pencil. I would also get up

without provocation and just spin around until I was overcome

with dizziness. I would announce that I was a tornado.” He strug¬

gled with mood swings even as a kid, and at age sixteen, while hos¬

pitalized for fainting spells, he jumped out of bed one night and

donned a white coat. "I went around to patient rooms and had

conversations as if I were a doctor. I was manic.”

During his first year at Boston College, he was hit by a bout of

severe depression. His was a classic case of true manic-depressive

illness, and Kraepelin would have recognized the course his illness

took over the next five years. "I didn't take medication," he ex¬

plains, and while he suffered several bouts of depression, he did well

in between those episodes, particularly when he was in a slightly hy-

pomanic state. "When I was feeling well, I would read more, and I

would write papers that weren't due for two or three months," he

says. "When you are hypomanic, your output is remarkable.” He

graduated with a double major in philosophy and English, with

nearly a straight-A average.

However, in his first year of graduate school at Stony Brook in

Long Island, he had a full-blown manic episode followed by a

plunge into depression that left him suicidal. It was then that he was

put on lithium and a tricyclic antidepressant for the first time. "I

didn't have mood swings after that, but instead of having a baseline

of functioning normally, I was depressed. I was in a state of depres-

THE BIPOLAR BOOM

199

sion the entire time I was on the medication. I stayed on it for a year

and said, 'No more.' "

Over the next two decades, Steve mostly stayed away from psy¬

chiatric medications. He married, had two sons, and divorced. He

worked, but skipped from job to job. His life was proceeding

down a chaotic path, a chaos that was clearly related to his manic-

depressive illness, and yet his life was not marked by vocational

disability— he always found work. In 1994, seeking relief from the

mood swings that plagued him, he began taking psychiatric

medications regularly. He cycled through an endless number of anti¬

depressants and mood stabilizers, none of which worked for long.

Those drug failures led to fourteen electroshock treatments, which

in turn left his memory so impaired that when he returned to his

job as a financial planner, "I could no longer recognize my best

client." In 1998, he was put on the tricyclic desipramine, which

promptly turned him into a rapid cycler. "I'd wake up and feel

great, completely emancipated from the demon of depression, and

then two days later, I am back into depression," he explains. "Two

days after that, I'm feeling well again. And there is nothing in my

external environment that would account for that change in

mood.”

He has been on SSDI ever since. The good news is that he hasn't

been hospitalized since 2000, and, as he rightly points out, in spite

of his constant battle with bipolar symptoms, he leads a productive

life. Remarried now, he volunteers as a "reader” for people who are

physically disabled, gives talks about bipolar illness to community

groups, and is one of the leaders of DBSA Boston. He also has pub¬

lished essays and poetry in various small publications. But when I

last spoke to him, in the spring of 2009, he was cycling through

multiple mood swings every day, his symptoms apparently continu¬

ing to worsen.

"I would say in the main, I have been worse when taking med¬

ication. The medication I am taking now is neutral at best. I wish I

could clone myself. I could be my own control group in a trial. I'd

like to know if I'd be better, the same, or worse without it."

200

ANATOMY OF AN EPIDEMIC

Brandon Banks

Brandon Banks can identify the precise moment he became "bipo¬

lar," and while it did involve an antidepressant, there was a series of

life events that led up to it. He grew up poor in Elizabethtown, Ken¬

tucky, without a father at home, and he has painful memories of

sexual abuse, physical abuse, and of a horrible car wreck that killed

his aunt, uncle, and another relative. At school, other kids regularly

taunted him about a facial birthmark, which so traumatized him

that he began wearing a hat pulled low on his head to cover it up.

After graduating from high school in 2000, he moved to Louisville,

where he went to college part-time and worked nights at United

Parcel Service. Soon he noticed that he "wasn't feeling right," and

when he went back home, his family doctor diagnosed him with

"moderate depression" and prescribed an antidepressant. "I went

manic in three days," Brandon says. "It was fast."

His doctor explained that since he'd had that reaction to the

drug, he must be bipolar, rather than just depressed. The drug had

"unmasked” the illness, which Brandon took as a positive thing.

"I'm thinking, This isn't so bad, I could have stayed in the system a

long time without getting immediate confirmation that I'm bipolar

like that.” He was put on a cocktail composed of a mood stabilizer,

an antidepressant, and an antipsychotic, and then it hit him. "This

was a serious shove into seriousness."

Over the next four years, his psychiatrists constantly changed his

prescriptions. "It was like musical chairs with the cocktails," he

says. "They would tell me, 'Let’s take this drug out and put this one

in.' " He took Depakote, Neurontin, Risperdal, Zyprexa, Seroquel,

Haldol, Thorazine, lithium, and an endless succession of antidepres¬

sants, and as time went on he became a rapid cycler who suffered

from mixed states. His medical records also document the develop¬

ment of new psychiatric symptoms: worsening anxiety, panic at¬

tacks, obsessive-compulsive behaviors, voices, hallucinations. He

was hospitalized several times, and at one point he climbed up on

top of a parking garage and threatened to jump off. His ability to

concentrate declined so severely that Kentucky took away his dri¬

ver's license. "What my life became was staying at home all day, get-

THE BIPOLAR BOOM

201

ting up in the morning and laying my pills out on the counter, tak¬

ing them, and then going back to sleep because I couldn't stay

awake if I tried. Then I would get up, play some video games, and

hang out with my family."

Twenty-four years old, he felt like a total failure, and one day,

after a fight with his mother, he moved out and stopped taking his

meds. "I deteriorated badly,” he recalls. "I wasn't bathing and I

wasn't eating.” However, as the weeks turned into months, his

bipolar symptoms lessened, and "I began to think that it's more like

I'm just fucked up," he says. This was a thought that gave him

hope, because now there was the possibility of change, and he took

off traveling around the South. "I might as well be homeless," he

told himself, and that journey ultimately turned into a transforma¬

tive experience. By the time he returned home, he had sworn off eat¬

ing meat and drinking alcohol, on his way to becoming a "health

freak" who practices yoga. "I came back from that trip, and man, I

was on top of it. I felt like a million dollars, and everyone in my

family— cousins, relatives, aunts and uncles —said that they hadn't

seen me glow like this since I was a kid.”

Since then, Brandon has stayed off psychiatric medications. But it

hasn't been easy, and the up-and-down nature of his life came into

sharp relief during his 2008-2009 year at Elizabethtown Commu¬

nity and Technical College. He enrolled there in January of 2008

with dreams of becoming a journalist and a writer, and in the fall,

he became managing editor of the school's newspaper. Under his

leadership, the newspaper won twenty-four awards from the Ken¬

tucky Intercollegiate Press Association during the 2008-2009 year,

and Brandon personally garnered ten such honors for the articles

he'd written, including first place in a deadline-writing competition.

Incredibly, during those nine months, Brandon racked up other suc¬

cesses too. One of his short stories won second place in a competi¬

tion and was published in a Louisville weekly; one of his photos was

picked as cover art for a literary journal; a short film he shot was

nominated for a best documentary award in a local film festival. In

May of 2009, his school honored him with its "outstanding sopho¬

more” award. Yet, even during this season of remarkable accom¬

plishment, Brandon suffered several hypomanic and depressive

202

ANATOMY OF AN EPIDEMIC

episodes that left him feeling deeply suicidal. "I spent several week¬

ends reading depressive authors with a gun in my hand,” he says.

"My accomplishments at these moments just seem to make every¬

thing worse. It never seems like enough.”

That is where matters stood in his life in the summer of 2009. He

was thriving and struggling at the same time, and his struggles were

such that if psychiatric medications had worked for him the first

time, he would gladly have turned to them for relief. "I'm still pretty

isolated from other people," he explains. "I stick out because of the

birthmark. I'm different. I can't blend in. It becomes an issue with

people. But I'm trying to integrate myself more into life. I have more

people in my life now than I have had in a long time. I'm starting to

make more contacts. I had lunch with a friend the other day. Doing

this is hard for me, and that's because it's just not easy for me to

deal with people and deal with my emotions. I am trying to get

better at it.”

Greg

A math and science whiz, Greg, who asked that I not use his last

name, was the sort of child who, when he was in junior high, built

a Van de Graaff generator from scrounged parts (which included a

vacuum cleaner and a salad bowl, to be precise). However, he had a

troubled relationship with his parents, and at the start of his senior

year, he began to slide into a mad state (and without having used il¬

legal drugs). "I was delusional, very paranoid, and full of anxiety,"

he says. "I was convinced that my parents were trying to kill me.”

Hospitalized for six weeks, Greg was told he was schizoaffective

with bipolar tendencies (a "manic-depressive” type diagnosis), and

he was discharged on a cocktail composed of two antipsychotics

and an antidepressant. But the drugs didn't chase away his paranoid

thoughts, and after he was hospitalized a second time, his psychia¬

trists added a mood stabilizer and a benzodiazepine to the cocktail

and told him he needed to give up his scholastic dreams. "They told

me I would be on medication for the rest of my life, and that I

would probably be a ward of the state, and that maybe, by the time

I was twenty-five or thirty, I could think about getting a part-time

THE BIPOLAR BOOM

203

job. And I believed it, and so I began trying to figure out how to live

with the crushing hopelessness that they are telling you is going to

be your life.”

The next five years passed pretty much as his psychiatrists had

predicted. Although Greg entered Worcester Polytechnic Institute

(WPI) in Massachusetts, he was so heavily medicated that, he says,

"I was living in a haze most of the time. Your mind is just a bag of

sand. And so I did really poorly in school. I rarely even left my

room, and I was kind of out of touch with reality.” He petered

along in school for a couple of years, not really making much

progress, and then, from 2004 to 2006, he dropped out and mostly

stayed in his apartment, smoking marijuana constantly, as "it

helped me accept the condition I was forced into." Six feet, five

inches tall, Greg's weight went from 255 pounds to nearly 500

pounds. "Finally, I said to myself, this is ridiculous. I'd rather be

crazy and have a life than not be crazy and not have a life.”

He went for a medical checkup, thinking this would be a first step

toward reducing his medications, only to be informed that he

needed to stop taking Depakote and Geodon right away, as his liver

was shutting down. The abrupt withdrawal induced such physical

pain — "sweats, joint and muscle pain, nausea, dizziness," he says —

that he didn't even pay attention to whether his paranoia was com¬

ing back. But in very short order, he was off all of his psychiatric

drugs, except for occasional use of a stimulant, and he had also

stopped smoking marijuana. "Honestly, it felt like I was waking up

for the first time in five years," he says. "It felt like I had been

turned off all those years and had just been rolling through life and

I was being pushed around in a wheelchair and finally I had woken

up and had gotten back to being myself again. I felt like the drugs

took away everything that was me, and then when I went off the

drugs, my brain woke up and started working again."

In late 2007, Greg went back to school. We met in the spring of

2009, and after he had told me the story of his bout with mental ill¬

ness, he showed me around his research laboratory at WPI, where

he now spent eighty hours a week, designing and constructing a

robot capable of conducting brain surgery inside an MRI. In a few

weeks, he would receive an undergraduate degree in mechanical en-

204

ANATOMY OF AN EPIDEMIC

gineering, and since he'd entered a master's program while still

doing undergraduate work, later that summer he would receive a

master's degree in mechatronics, which is a fusion of mechanical

and electrical engineering. The day before my visit, his robotics

research had won second prize in a competition that featured 187

entries by graduate students at WPI. Already he had published three

papers in academic journals on his project, and in a few weeks he

was scheduled to fly to Japan to give a talk about it. He was doing

this project under the guidance of a WPI professor, and they ex¬

pected to conduct animal and cadaver trials with the robot in the

fall of 2009. If all went well, clinical trials with humans would

begin in two years.

While in his laboratory, Greg showed me the robot and the

computer drawings of its circuit boards, which seemed impossibly

complex. Naturally, I thought of John Nash, the Princeton mathe¬

matician whose inspiring story of recovering from schizophrenia,

and doing so while off medication, was told in the book A Beautiful

Mind. "I still feel that I have some bad habits to get out of and some

better habits to get into before I get into the professional life, but I

really do feel that I have left that [mentally ill] part of my life

behind,” says Greg, who has lost more than one hundred pounds.

"Honestly, I almost never think of it. I now think of myself as a per¬

son who is susceptible to building anxiety, but when I start feeling

this anxiety, or start feeling negative about things, I stop and say to

myself, 'Are these really reasonable feelings to feel, or is it just inse¬

curity?' I just have to take the time to check myself.” He is, he

concluded, "pretty optimistic about my future now.”

An Epidemic Explained

"With psychiatric medications, you solve one

problem for a period of time, but the next thing you

know you end up with two problems. The treatment

turns a period of crisis into a chronic mental illness."

— AMY UPHAM (2009)

There is a famous optical illusion called the young lady and the old

hag, and depending on how you look at it, you see either a beautiful

young woman or an old witch. The drawing illustrates how one's

perception of an object can suddenly flip, and in a sense, the dueling

histories that we have fleshed out in this book have that same curi¬

ous quality. There is the "young woman" picture of the psycho¬

pharmacology era that most of American society believes in, which

tells of a revolutionary advance in the treatment of mental disor¬

ders, and then there is the "old hag” picture that we have sketched

out in this book, which tells of a form of care that has led to an

epidemic of disabling mental illness.

The young-lady picture of the psychopharmacology era arises

from a powerful combination of history, language, science, and clin¬

ical experience. Prior to 1955, history tells us, the state mental hos¬

pitals were bulging with raving lunatics. But then researchers

discovered an antipsychotic medication, Thorazine, and that drug

made it possible for the states to close their decrepit hospitals and

to treat schizophrenics in the community. Next, psychiatric re¬

searchers discovered anti-anxiety agents, antidepressants, and a

magic bullet —lithium —for bipolar disorder. Science then proved

that the drugs worked: In clinical trials, the drugs were found to

206

ANATOMY OF AN EPIDEMIC

Young or old woman? If you shift your eyes slightly, your perception of the

image will change from one to the other. Courtesy of Exploratorium.

ameliorate a target symptom over the short term better than

placebo. Finally, psychiatrists regularly saw that their drugs were

effective. They gave them to their distressed patients, and their

symptoms often abated. If their patients stopped taking the drugs,

their symptoms frequently returned. This clinical course —initial

symptom reduction and relapse upon drug withdrawal —also gave

patients reason to say: "I need my medication. I can't do well with¬

out it.”

The old-hag picture of the psychopharmacology era arises from a

more careful reading of history and a more thorough review of the

science. When we reviewed the history of deinstitutionalization, we

found that the discharge of chronic schizophrenia patients resulted

from the enactment of Medicare and Medicaid legislation in the

mid-1960s, as opposed to from Thorazine's arrival in asylum medi¬

cine. As for the drugs, we discovered that there was no scientific

breakthrough that led to the introduction of Thorazine and other

first-generation psychiatric medications. Instead, scientists studying

compounds for use as anesthetics and as magic bullets for infectious

AN EPIDEMIC EXPLAINED

207

diseases stumbled upon several agents that had novel side effects.

Then, over the course of the next thirty years, researchers deter¬

mined that the drugs work by perturbing the normal functioning of

neuronal pathways in the brain. In response, the brain undergoes

"compensatory adaptations” to cope with the drug's mucking up of

its messaging system, and this leaves the brain functioning in an

"abnormal" manner. Rather than fix chemical imbalances in the

brain, the drugs create them. We then combed through the out¬

comes literature, and we found that these pills worsen long-term

outcomes, at least in the aggregate. Researchers even put together

biological explanations for why the drugs had this paradoxical

long-term effect.

Those are the dueling visions of the psychopharmacology era. If

you think of the drugs as "anti-disease” agents and focus on short¬

term outcomes, the young lady springs into sight. If you think of the

drugs as "chemical imbalancers" and focus on long-term outcomes,

the old hag appears. You can see either image, depending on where

you direct your gaze.

A Quick Thought Experiment

Just for a moment, before we examine whether we have solved the

puzzle that we set forth in the opening of this book, here is a quick

way to see the old-hag picture a bit more clearly. Imagine that a

virus suddenly appears in our society that makes people sleep

twelve, fourteen hours a day. Those infected with it move about

somewhat slowly and seem emotionally disengaged. Many gain

huge amounts of weight —twenty, forty, sixty, and even one hun¬

dred pounds. Often, their blood sugar levels soar, and so do their

cholesterol levels. A number of those struck by the mysterious ill¬

ness-including young children and teenagers —become diabetic in

fairly short order. Reports of patients occasionally dying from pan¬

creatitis appear in the medical literature. Newspapers and maga¬

zines fill their pages with accounts of this new scourge, which is

dubbed metabolic dysfunction illness, and parents are in a panic

208

ANATOMY OF AN EPIDEMIC

over the thought that their children might contract this horrible

disease. The federal government gives hundreds of millions of

dollars to scientists at the best universities to decipher the inner

workings of this virus, and they report that the reason it causes such

global dysfunction is that it blocks a multitude of neurotransmitter

receptors in the brain —dopaminergic, serotoninergic, muscarinic,

adrenergic, and histaminergic. All of those neuronal pathways in

the brain are compromised. Meanwhile, MRI studies find that over

a period of several years, the virus shrinks the cerebral cortex, and

this shrinkage is tied to cognitive decline. A terrified public clamors

for a cure.

Now such an illness has in fact hit millions of American children

and adults. We have just described the effects of Eli Lilly's best¬

selling antipsychotic, Zyprexa.

A Mystery Solved

We began this book by raising a question: Why have we seen such a

sharp increase in the number of disabled mentally ill in the United

States since the "discovery” of psychotropic medications? At the

very least, I think we have identified one major cause. In large part,

this epidemic is iatrogenic in kind.

Now there may be a number of social factors contributing to the

epidemic. Our society may be organized in a way today that leads to

a great degree of stress and emotional turmoil. For instance, we may

lack the close-knit neighborhoods that help people stay well. Rela¬

tionships are the foundation of human happiness, or so it seems,

and as Robert Putnam wrote in 2000, we spend too much time

"bowling alone.” We also may watch too much television and get

too little exercise, a combination that is known to be a prescription

for becoming depressed. The food we eat —more processed foods

and so on —might be playing a role too. And the common use of

illicit drugs —marijuana, cocaine, and hallucinogens —has clearly

contributed to the epidemic. Finally, once a person goes on SSI or

SSDI, there is a tremendous financial disincentive to return to work.

AN EPIDEMIC EXPLAINED

209

People on disability call it the "entitlement trap.” Unless they can

get a job that pays health insurance, they will lose that safety net if

they go back to work, and once they start working, they may lose

their rent subsidy, too.

However, in this book, we have been focusing on the role that

psychiatry and its medications may be playing in this epidemic, and

the evidence is quite clear. First, by greatly expanding diagnostic

boundaries, psychiatry is inviting an ever-greater number of chil¬

dren and adults into the mental illness camp. Second, those so diag¬

nosed are then treated with psychiatric medications that increase

the likelihood they will become chronically ill. Many treated with

psychotropics end up with new and more severe psychiatric symp¬

toms, physically unwell, and cognitively impaired. That is the tragic

story writ large in five decades of scientific literature.

The record of disability produced by psychiatric medications can

be easily summarized. With schizophrenia, in the decade prior to

the introduction of Thorazine, roughly 70 percent of people suffer¬

ing a first episode of psychosis were discharged from the hospital

within eighteen months, and the majority didn't return to the hospi¬

tal during fairly lengthy follow-up periods. Researchers in the post-

Thorazine era reported similar results for unmedicated patients.

Rappaport, Carpenter, and Mosher all found that perhaps half of

those diagnosed with schizophrenia would do fairly well if they

were not continuously medicated. But that is now the standard of

care, and as Harrow's study showed, only 5 percent of medicated

patients recover over the long term. Today, there are an estimated 2

million adults disabled by schizophrenia in the United States, and

this disability number could perhaps be halved if we adopted a

paradigm of care that employed antipsychotic medications in a

selective, cautious manner.

With the affective disorders, the iatrogenic effects of our drug-

based paradigm of care are even more apparent. Anxiety used to be

viewed as a mild disorder, one that rarely required hospitalization.

Today, 8 percent of the younger adults on the SSI and SSDI roles

due to a psychiatric disability have anxiety as a primary diagnosis.

Similarly, outcomes for major depression used to be good. In 1955,

there were only thirty-eight thousand people hospitalized with de-

210

ANATOMY OF AN EPIDEMIC

pression, and the illness could be expected to remit. Today, major

depression is the leading cause of disability in the United States for

people fifteen to forty-four years old. It is said to strike 15 million

adults, and according to researchers at Johns Hopkins School of

Public Health, 60 percent are "severely impaired.” As for bipolar

disorder, an extremely rare illness has become a common one.

According to the NIMH, nearly 6 million adults suffer from it

today. Whereas 85 percent of those struck by it used to recover and

go back to work, now only about a third of bipolar patients func¬

tion this well, and over the long term those bipolar patients who

reliably take their medications end up nearly as impaired as those

with schizophrenia who stay on neuroleptics. The Johns Hopkins

investigators concluded that 83 percent are "severely impaired.”

In sum, there were fifty-six thousand people hospitalized with

anxiety and manic-depressive illness in 1955. Today, according to

the NIMH, at least 40 million adults suffer from one of these affec¬

tive disorders. More than 1.5 million people are on SSI or SSDI

because they are disabled by anxiety, depression, or bipolar illness,

and, according to the Johns Hopkins data, more than 14 million

people who have these diagnoses are "severely impaired” in their

ability to function in society. That is the astonishing bottom-line

result produced by a medical specialty that has dramatically ex¬

panded diagnostic boundaries in the past fifty years and treated its

patients with drugs that perturb normal brain function.

Moreover, the epidemic continues its march. In the eighteen

months it took me to research and write this book, the Social Secu¬

rity Administration released its 2007 reports for its SSI and SSDI

programs, and the numbers were as expected. There were 401,255

children and adults under sixty-five years old added to the SSI and

SSDI rolls in 2007 because of a psychiatric disability. Imagine a

large auditorium filling up every day with 250 children and 850

adults newly disabled by mental illness, and you get a visual sense of

the horrible toll exacted by this epidemic.

AN EPIDEMIC EXPLAINED

211

Physical Illness, Cognitive Impairment,

and Early Death

Fleshing out the nature of a disease usually involves identifying all

the symptoms that may develop, and then following their course

over time. In the previous chapters, we mostly focused on studies

that showed that psychiatric medications worsen target symptoms

over the long run, and only briefly noted that the drugs may cause

physical problems, emotional numbing, and cognitive impairment.

This is also a form of care that leads to early death. The seriously

mentally ill are now dying fifteen to twenty-five years earlier than

normal, with this problem of early death having become much more

pronounced in the past fifteen years. 2 They are dying from cardio¬

vascular ailments, respiratory problems, metabolic illnesses, dia¬

betes, kidney failure, and so forth —the physical ailments tend to

pile up as people stay on antipsychotics (or drug cocktails) for years

on end. 2

Here are three stories that bear witness to these various long¬

term risks.

Amy Up ham

Amy Upham lives in a small one-bedroom apartment in Buffalo,

and as I enter the living room, she points to a table cluttered with

papers. "This is me on psychiatric drugs," she says and hands me a

stack of medical documents. They tell of a drug-induced swelling of

the brain, faltering kidneys, a swollen liver, a swollen gallbladder,

thyroid problems, gastritis, and cognitive abnormalities. A little

over five feet tall, with frizzy reddish brown hair, Amy, who is thirty

years old, weighs ninety pounds. She squeezes a fold of loose skin

near her elbow, the muscle underneath having wasted away. "This

is like what you see with heroin users."

Amy first took a psychiatric medication at age sixteen when she

contracted Lyme disease and suffered a bout of depression. Twelve

years later, she was still on antidepressants, and as she reviews

that history, she identifies several instances when the drugs stirred

212

ANATOMY OF AN EPIDEMIC

hypomanic episodes and worsened her obsessive-compulsive behav¬

iors. Finally, in 2007, she decided to gradually wean herself from

the two-drug combo she was taking, and at first, it went well. How¬

ever, at the time, she was working for the county mental health

department as an advocate for the mentally ill, and eventually

someone anonymously informed her bosses that she was going off

her medication. This went against what the agency preached, and it

all ended with Amy out of a job and paranoid that someone was

stalking her. "I had a nervous breakdown," she says. "I went into

the hospital to hide.”

This was the first time Amy had ever been hospitalized, and she

was immediately put on a cocktail that included lithium. Within a

few months, her endocrine system began to fail. Her menstrual cycle

ceased, her thyroid went haywire, and an EEG revealed that her

brain was swollen. Then her kidneys started shutting down. She had

to abruptly stop taking the lithium, and that triggered a manic

episode. Doctors put her on Ativan to counter the mania, but that

drug stirred feelings of horrible rage and left her feeling suicidal.

Months passed, and in December 2008, she checked herself into a

psych hospital, where she was diagnosed with Ativan toxicity. "I've

never seen a drug fuck up a person like Ativan fucks you up,” a

nurse told her. The hospital switched her from Ativan to Klonopin

and prescribed Ability, which triggered a seizure. Next a doctor dis¬

covered something wrong with her heart, which appeared to be re¬

lated to the Klonopin, and so Amy was put back on Ativan. "Now I

start hallucinating for the first time in my life," she says. "I was pac¬

ing uncontrollably and crawling out of my skin." Other drug-related

complications ensued, and on February 24, 2009, Amy moved into a

shelter on the hospital grounds, her thoughts now so scattered that a

nurse wondered "if early Alzheimer's runs in the family."

Remarkably, much of that story is documented in the sheaf of pa¬

pers that Amy has given me. She spent the last four months trying to

get off the Ativan, but every time she dropped to a lower dose, she

suffered fits of rage and something akin to delirium. "I am feeling

scared," she says, as I hand the papers back to her. "The with¬

drawals are really bad and I live alone. I'm in a constant state of

panic, anxiety, and I have some agoraphobia. It's not safe.”

AN EPIDEMIC EXPLAINED

213

Rachel Klein

When I first met Rachel Klein in the spring of 2008, she hobbled

into my office with a cane and a service dog by her side, which

flopped by her feet while we spoke. She was not yet forty years old,

but very quickly she rewound the clock for me, and soon she was

telling of a bright fall day in 1984. Only sixteen years old, she was

entering the Massachusetts Institute of Technology, a child prodigy

with an IQ of 173 and her ears ringing with predictions that one

day she would win a Nobel Prize. "I arrived on campus with a

teddy bear sticking out of my backpack," she says, smiling slightly

at the memory. "That's how ill-equipped emotionally I was."

Rachel's emotional crash at MIT got under way at the end of her

sophomore year, when she became involved with an older student

who was "totally psychotic” and she began using illicit drugs —

Ecstasy, acid, mushrooms, and nitrous oxide. Her sense of self

began to crumble, and after a summer of talk therapy left her more

confused than ever, she was hospitalized for psychotic depression.

When she was released, she had prescriptions for an antipsychotic,

an antidepressant, and a benzodiazepine (Xanax). "None of those

drugs helped me," she says. "They numbed me out, and trying to

get off Xanax was a disaster. That is the evilest drug ever. It is so ad¬

dictive, and all of the symptoms that caused you to go into the hos¬

pital in the first place get one thousand times worse when you try to

go off it."

Although Rachel eventually graduated from MIT and was ac¬

cepted into an M.D.-Ph.D. program at the University of Colorado,

she began cycling in and out of hospitals; her crash at MIT trans¬

formed into a case of chronic mental illness. "They told me I was

hopeless, and that I would never get better," she recalls. She enjoyed

a period of stability from 1995 to 2001, when she worked as an as¬

sistant house manager at a group home in Boston, but then her

brother died suddenly and her psychological problems flared up

anew. Her psychiatrist took her off Risperdal and switched her to

high doses of Geodon and Effexor, and he gave her an injection of

another psychiatric medication as well.

"I had a severe serotonergic reaction, a toxic reaction," Rachel

2 14

ANATOMY OF AN EPIDEMIC

says, shaking her head at the memory. "It caused vasoconstriction

in my brain, and this caused brain damage. I ended up in a wheel¬

chair, and I couldn't think, speak, or walk. Those centers of the

brain need a lot of juice."

Since then, her life has had its ups and downs. She takes comfort

in her volunteer work with M-Power, the Boston peer advocacy

group, and in the spring of 2008, she was working sixteen hours a

week for Advocates, Inc., which provides services to the deaf. But

she also has battled ovarian cancer, and it's possible that illness was

related to the psychiatric medications. She does find such drugs use¬

ful today, but when she looks back at her life, she sees a paradigm of

care that utterly failed her. "It's really a travesty," she says.

Scott Sexton

In the spring of 2005, Scott Sexton received his MBA from Rice

University. A bright future lay ahead at that moment, but then he

broke up with the woman he had intended to marry, and he was

hospitalized for depression. This was his second bout of major de¬

pression (he'd suffered a first episode five years earlier, when his par¬

ents divorced), and since Scott's father had suffered from bipolar

illness, he was now diagnosed with that disorder. He was put on a

cocktail that included Zyprexa.

That fall, he began working as a consultant for Deloitte, the big

accounting firm. Although his first few months on the job went fine,

by early 2006 he was sleeping twelve to sixteen hours a day, zonked

out by the Zyprexa. He soon needed another pill to get up in the

morning, and he began "putting on weight like gangbusters,” his

mother, Kaye, recalls. "He was five feet, ten inches tall and he went

from 185 pounds to 250 pounds. He had a beer belly, and his

cheeks looked like he was a chipmunk. We knew that Zyprexa

caused weight gain, and he was alarmed, and so was I."

By the fall of 2006, Scott was sleeping so much that on weekends

he wouldn't get up until the afternoon. He stopped going into

the office and told Deloitte he was working from home. On Thanks¬

giving, he called his mother to tell her that he was suffering severe

stomach pains, and the next day he was admitted to St. Luke's

AN EPIDEMIC EXPLAINED

215

Episcopal Hospital in Houston. His mother flew in from Midland.

"Scott is beet red, he's sweating, and his hands are so swollen that

they have trouble getting his ring off. He is burning up, and his [lab¬

oratory] tests are wacko. They are off the wall. His cholesterol is

sky-high. His triglycerides are off the charts."

Scott's pancreas was shutting down. Zyprexa was known to

cause pancreatitis, but the doctors at St. Luke's didn't connect the

dots. They kept Scott on that drug until his death on December 7. "I

had always told him to take his meds," his mother says. "I said,

'Scott, if I ever find out you are off your meds, I will come to Hous¬

ton and shoot you.' That's what I said to him. And here he is doing

everything he thinks he needs to do to be functional in our society,

to be a productive member of society, and it kills him.”

The Epidemic Spreads to Children

"For many parents and families, the experience (of

having a child diagnosed with a mental illness] can be

a disaster; we must say that.

-E. JANE COSTELLO, PROFESSOR OF PSYCHIATRY AT

DUKE UNIVERSITY ( 2 0 0 6 )'

The prescribing of psychiatric drugs to children and adolescents is a

recent phenomenon, as relatively few youth were medicated prior to

1980, and so as we investigate this story, we have an opportunity to

put the thesis of this book to a second test. Do we find, in the scien¬

tific literature and in societal data, that the medicating of children and

teenagers is doing more harm than good? Is it putting many children,

who initially may be struggling with a relatively minor problem —a

disinterest in school, or a bout of sadness —onto a path that leads to

lifelong disability? One of the principles of science is that the re¬

sults from an experiment should be replicable, and in essence the

medicating of children makes for a second experiment. First we

medicated adults diagnosed with mental illness, and as we saw in the

previous chapters, that did not lead to good long-term outcomes.

Next, over the past thirty years, we diagnosed children and adoles¬

cents with various disorders and put them on psychiatric drugs, and

now we can see if the results this second time around are the same.

I realize that this frames our investigation of the medicating

of children in a rather cold, analytical way, given the frightening

possibility at stake here. If the outcomes are the same in children

and teenagers as in adults, then the prescribing of psychiatric drugs

to millions of American youth is causing harm on an almost

THE EPIDEMIC SPREADS TO CHILDREN

2ly

unfathomable scale. But that possibility lends itself to an emotional

review of the medical literature, which is precisely why we are going

to conduct our inquiry in the most dispassionate manner possible.

We need the facts to speak for themselves.

The story of progress that psychiatry tells about the medicating

of children is slightly different in kind from the one it tells about its

advances in care for adults. In 1955, when Thorazine arrived, there

were hundreds of thousands of adults in mental hospitals, and they

were diagnosed with illnesses that had a recognizable past. But

when the psychopharmacology era began, very few children were

diagnosed as "mentally ill." There were bullies and goof-offs in ele¬

mentary schools, but they were not diagnosed with attention-deficit/

hyperactivity disorder (ADHD), as that diagnosis had yet to be

born. There were moody and emotionally volatile teenagers, but so¬

ciety's expectation was that they would grow up into more-or-less

normal adults. However, once psychiatry began treating children

with psychotropic medications, it rethought that view of childhood.

The story that psychiatry now tells is that during the past fifty years

it discovered that children regularly suffer from mental illnesses,

which are said to be biological in kind. First psychiatry fleshed out

ADHD as an identifiable disease, and then it determined that major

depression and bipolar illness regularly struck children and adoles¬

cents. Here's how Harvard Medical School psychiatrist Ronald

Kessler summed up this "history" in 2 001:

Although epidemiological studies of child and adolescent

mood disorders have been carried out for many years,

progress long was hampered by two misconceptions: that

mood disorders are rare before adulthood and that mood dis¬

turbance is a normative and self-limiting aspect of child and

adolescent development. Research now makes it clear that

neither of these beliefs is true. Depression, mania, and mania¬

like symptoms are all comparatively common among children

and adolescents in the general population." 2

Illnesses that used to go undetected, it seems, have now been

identified. The second part of this story of scientific progress tells of

2 1 8 •

ANATOMY OF AN EPIDEMIC

how psychiatric medications are both helpful and necessary.

Millions of children who used to suffer in silence are now getting

treatment that helps them thrive. Indeed, the story now emerging in

pediatric psychiatry is that psychotropic medications help create

healthy brains. In his 2006 book Child and Adolescent Psycho-

pharmacology Made Simple, psychiatrist John O'Neal explained to

readers why it was so essential that children with mental illness be

treated with medication:

Increasing evidence shows that some psychiatric disorders are

subject to progressive neurobiological impairment if they go

untreated. . . . Toxic levels of neurotransmitters, such as gluta¬

mates, or stress hormones, such as Cortisol, may damage neural

tissue or interfere with normal pathways of neuromaturation.

Pharmacological treatment of those disorders may be not only

successful in improving symptoms, but also neuroprotective (in

other words, medical treatments may either protect against

brain damage or promote normal neuromaturation)." 3

If this is true, psychiatry has indeed made a great leap ahead

in the past thirty years. The field has learned to diagnose brain

illnesses in children that used to go unnoticed, and its "neuro¬

protective" drugs now turn them into normal adults.

The Rise of ADHD

Although attention-deficit disorder did not show up in psychiatry's

Diagnostic and Statistical Manual until 1980, the field likes to point

out that it didn't just appear out of thin air. This is a disorder that

traces its medical roots back to 1902. That year, Sir George Freder¬

ick Still, a British pediatrician, published a series of lectures on

twenty children who were of normal intelligence but "exhibited vio¬

lent outbursts, wanton mischievousness, destructiveness, and a lack

of responsiveness to punishment." 4 Moreover, he reasoned that

their bad behavior arose from a biological problem (as opposed to

THE EPIDEMIC SPREADS TO CHILDREN

219

bad parenting). Children with known diseases —epilepsy, brain tu¬

mors, or meningitis —were often aggressively defiant, and thus Still

figured that these twenty children suffered from "minimal brain

dysfunction,” even though there was no obvious illness or trauma

that had caused it.

Over the next fifty years, a handful of others advanced the notion

that hyperactivity was a marker for brain injury. Children who re¬

covered from encephalitis lethargica, a viral epidemic that swept

around the globe from 1917 to 1928, often exhibited antisocial be¬

haviors and severe emotional swings, leading pediatricians to con¬

clude that the illness had caused mild brain damage, even though

the nature of that damage couldn't be identified. In 1947, Alfred

Strauss, who was the director of a school for disturbed youth in

Racine, Wisconsin, called his extremely hyperactive students "nor¬

mal brain injured children." 5 Psychiatry's first Diagnostic and Sta¬

tistical Manual, published in 1952, said such children suffered from

an "organic brain syndrome.”

The notion that stimulants might be beneficial for such children

arose in 1937, when Charles Bradley gave a newly synthesized am¬

phetamine, Benzedrine, to hyperactive children who complained of

headaches. Although the drug didn't cure their head pain, Bradley

reported that it "subdued” the children and helped them concen¬

trate better on their schoolwork. The children dubbed Benzedrine

the "arithmetic pill."" Although his report was mostly forgotten

for the next twenty years, in 1956 Ciba-Geigy brought Ritalin

(methylphenidate) to market as a treatment for narcolepsy, touting

it as a "safe” alternative to amphetamines, and physicians at Johns

Hopkins University School of Medicine, who were aware of

Bradley's findings, soon deemed this new drug useful for quieting

"disturbed" children who were thought to be suffering from a

"brain damage syndrome." 7

There was no great rush by psychiatrists during the 1960s to pre¬

scribe Ritalin to fidgety children who went to regular schools. At

that time, there was a sense that psychoactive drugs, because of

their many risks, should be administered only to hospitalized chil¬

dren, or children in residential facilities. The population of children

so hyperactive that they might be diagnosed with "organic brain

220

ANATOMY OF AN EPIDEMIC

dysfunction" was small. However, psychiatry's use of Ritalin slowly

began to climb during the 1970s, such that by the end of the decade

perhaps 150,000 children in the United States were taking the drug.

Then, in 1980, the field published a third edition of its Diagnostic

and Statistical Manual (DSM-III), and it identified "attention-deficit

disorder" as a disease for the first time. The cardinal symptoms were

"hyperactivity,” "inattention," and "impulsivity," and given that

many children fidget in their seats and have trouble paying attention

in school, the diagnosis of ADD began to take off. In 1987, psy¬

chiatry further loosened the diagnostic boundaries, renaming it

attention-deficit/hyperactivity disorder in a revised edition of DSM-

III. Next, Ciba-Geigy helped fund Children and Adults with Atten¬

tion Deficit Hyperactivity Disorder (CHADD), a "patient-support

group” that immediately began promoting public awareness of this

"disease.” Finally, in 1991, CHADD successfully lobbied Congress

to include ADHD as a disability that would be covered by the Indi¬

viduals with Disabilities Education Act. Children diagnosed with

ADHD were now eligible for special services, which were to be

funded with federal money, and schools regularly began identifying

children who seemed to have this condition. As the Harvard Review

of Psychiatry noted in 2009, even today the diagnosis of ADHD

arises primarily from teacher complaints, as "only a minority of

children with the disorder exhibit symptoms during a physician's

office visit." 8

Suddenly, ADHD children could be found in every classroom.

The number of children so diagnosed rose to nearly 1 million in

1990, and more than doubled over the next five years. Today,

perhaps 3.5 million American children take a stimulant for ADHD,

with the Centers for Disease Control reporting in 2 007 that one

in every twenty-three American children four to seventeen years

old is so medicated. This prescribing practice is mostly a U.S.

phenomenon —children here consume three times the quantity of

stimulants consumed by the rest of the world's children combined.

Although the public often hears that research has shown that

ADHD is a "brain disease,” the truth is that its etiology remains

unknown. "Attempts to define a biological basis for ADHD have

been consistently unsuccessful," wrote pediatric neurologist Gerald

THE EPIDEMIC SPREADS TO CHILDREN

221

Golden in 1991. "The neuroanatomy of the brain, as demonstrated

by imaging studies, is normal. No neuropathologic substrate has

been demonstrated." 9 Seven years later, a panel of experts convened

by the National Institutes of Health reiterated this same point:

"After years of clinical research and experience with ADHD, our

knowledge about the cause or causes of ADHD remains largely

speculative." 10 During the 1990s, CHADD advised the public that

children with ADHD suffered from a chemical imbalance, charac¬

terized by an underactive dopamine system, but that was simply

a drug-marketing claim. Ritalin and other stimulants increase

dopamine levels in the synaptic cleft, and thus CHADD was at¬

tempting to make it seem that such drugs "normalized" brain

chemistry, but, as the American Psychiatric Press's 1997 Textbook of

Neuropsychiatry confessed, "efforts to identify a selective neuro¬

chemical imbalance [in ADHD children] have been disappointing.” 11

So we see in this history that nothing new was discovered that

told of a "mental illness" called ADHD. There was a long record of

speculation within medicine that extremely hyperactive children suf¬

fered from brain dysfunction of some kind, which was certainly a

reasonable thought, but the nature of that dysfunction was never dis¬

cerned, and then, in 1980, psychiatry simply created, with a stroke of

its pen in DSM-III, a dramatically expanded definition of "hyperac¬

tivity.” The fidgety seven-year-old boy who might have been dubbed

a "goof-off" in 1970 was now suffering from a psychiatric disorder.

Given that the biology of ADHD remains unknown, it is fair to

say that Ritalin and other ADHD drugs "work” by perturbing

neurotransmitter systems. Ritalin could best be described as a

dopamine reuptake inhibitor. At a therapeutic dose, it blocks 70

percent of the "transporters" that remove dopamine from the

synaptic cleft and bring it back into the presynaptic neuron. Co¬

caine acts on the brain in the same way. However, methylphenidate

clears much more slowly from the brain than cocaine does, and thus

it blocks dopamine reuptake for hours, as opposed to cocaine's rel¬

atively brief disruption of this function. 10

* The fact that cocaine is so short-acting is why it is more addictive than

methylphenidate, for as soon as it leaves the brain, the addict may want to

222

ANATOMY OF AN EPIDEMIC

In response to methylphenidate, the child's brain goes through a

series of compensatory adaptations. Dopamine is now remaining in

the synaptic cleft too long, and so the child's brain dials down its

dopamine machinery. The density of dopamine receptors on the

postsynaptic neurons declines. At the same time, the amount of

dopamine metabolites in the cerebrospinal fluid drops, evidence that

the presynaptic neurons are releasing less of it. Ritalin also acts on

serotonin and norepinephrine neurons, and that causes similar com¬

pensatory changes in those two pathways. Receptor densities for

serotonin and norepinephrine decline, and the output of those two

chemicals by presynaptic neurons is altered as well. The child's brain

is now operating, as Steven Hyman said, in a manner that is "quali¬

tatively as well as quantitatively different from the normal state." 12

Now we can turn our attention to the outcomes data. Does this

treatment help children diagnosed with ADHD over the long term?

What does the scientific literature show?

Passive, Sitting Still, and Alone

Ritalin and other ADHD drugs do reliably change a child's behav¬

ior, and in his 1937 report, Charles Bradley set the stage for the effi¬

cacy story that eventually emerged: "Fifteen of the thirty children

responded to Benzedrine by becoming distinctly subdued in their

emotional responses. Clinically in all cases this was an improvement

from the social viewpoint." 15 Ritalin, which the FDA approved for

use in children in 1961, was found to have a similar subduing effect.

In a 1978 double-blind study, Ohio State University psychologist

Herbert Rie studied twenty-eight "hyperactive" children for three

months, half of whom were prescribed methylphenidate. Here is

what he wrote:

experience again the "rush" that comes when dopaminergic pathways are first

sent into a hyperactive state.

THE EPIDEMIC SPREADS TO CHILDREN

223

Children who were retrospectively confirmed to have been on

active drug treatment appeared, at the times of evaluation,

distinctly more bland or "flat” emotionally, lacking both the

age-typical variety and frequency of emotional expression.

They responded less, exhibited little or no initiative or spon¬

taneity, offered little indication of either interest or aversion,

showed virtually no curiosity, surprise, or pleasure, and

seemed devoid of humor. Jocular comments and humorous

situations passed unnoticed. In short, while on active drug

treatment, the children were relatively but unmistakably

affectless, humorless, and apathetic. 11

Numerous investigators reported similar observations. Children

on Ritalin show "a marked drug-related increase in solitary play

and a corresponding reduction in their initiation of social interac¬

tions,” announced Russell Barkley, a psychologist at the Medical

College of Wisconsin, in 1978.” This drug, observed Bowling

Green State University psychologist Nancy Fiedler, reduced a child's

"curiosity about the environment." 16 At times, the medicated child

"loses his sparkle," wrote Canadian pediatrician Till Davy in

1989. 17 Children treated with a stimulant, concluded a team of

UCLA psychologists in 1993, often become "passive, submissive”

and "socially withdrawn." 18 Some children on the drug "seem

zombie-like,” noted psychologist James Swanson, director of an

ADHD center at the University of California, Irvine.' 9 Stimulants,

explained the editors of the Oxford Textbook of Clinical Psycho-

phamacology and Drug Therapy, curb hyperactivity by "reducing

the number of behavioral responses." 10

All of these reports told the same story. On Ritalin, a student

who previously had been an annoyance in the classroom, fidgeting

too much in his or her chair or talking to a nearby classmate while

the teacher scribbled on the blackboard, would be stilled. The stu¬

dent wouldn't move around as much and wouldn't engage as much

socially with his or her peers. If given a task like answering arith¬

metic problems, the student might focus intently on it. Charles

Bradley thought this change in behavior was "an improvement

from the social viewpoint," and it is that perspective that shows up

224

ANATOMY OF AN EPIDEMIC

in efficacy trials of Ritalin and other ADHD drugs. Teachers and

other observers fill out rating instruments that view a reduction in

the child's movements and engagement with others as positive, and

when the results are tabulated, 70 to 90 percent of the children are

reported to be "good responders" to ADHD medications. These

drugs, NIMH investigators wrote in 1995, are highly effective in

"dramatically reducing a range of core ADHD symptoms such as

task-irrelevant activity (e.g., finger tapping, fidgetiness, fine motor

movement, off-task [behavior] during direct observation) and class¬

room disturbance." 21 ADHD experts at Massachusetts General

Hospital summed up the scientific literature in a similar way: "The

extant literature clearly documents that stimulants diminish behav¬

iors prototypical of ADHD, including motoric overactivity, impul-

sivity, and inattentiveness."”

However, none of this tells of drug treatment that benefits the

child. Stimulants work for the teacher, but do they help the child?

Here, right from the start, researchers ran into a wall. "Above all

else,” wrote Esther Sleator, a physician at the University of Illinois

who asked fifty-two children what they thought of Ritalin, "we

found a pervasive dislike among hyperactive children for taking

stimulants." 2 ' Children on Ritalin, University of Texas psychologist

Deborah Jacobvitz reported in 1990, rated themselves as "less

happy and [less] pleased with themselves and more dysphoric."

When it came to helping a child make friends and sustain friend¬

ships, stimulants produced "few significant positive effects and a

high incidence of negative effects," Jacobvitz said. 24 Other re¬

searchers detailed how Ritalin harmed a child's self-esteem, as the

children felt they must be "bad” or "dumb" if they had to take such

a pill. "The child comes to believe not in the soundness of his own

brain and body, not in his own growing ability to learn and to con¬

trol his behavior, but in 'my magic pills that make me into a good

boy,' " said University of Minnesota psychologist Alan Sroufe. 25

All of this told of harm done, of a drug that made a child de¬

pressed, lonely, and filled with a sense of inadequacy, and when

researchers looked at whether Ritalin at least helped hyperactive

children fare well academically, to get good grades and thus succeed

as students, they found that it wasn't so. Being able to focus intently

THE EPIDEMIC SPREADS TO CHILDREN

225

on a math test, it turned out, didn't translate into long-term aca¬

demic achievement. This drug, Sroufe explained in 1973, enhances

performance on "repetitive, routinized tasks that require sustained

attention," but "reasoning, problem solving and learning do not

seem to be [positively] affected." 26 Five years later, Herbert Rie was

much more negative. He reported that Ritalin did not produce any

benefit on the students' "vocabulary, reading, spelling, or math,"

and hindered their ability to solve problems. "The reactions of the

children strongly suggest a reduction in commitment of the sort that

would seem critical for learning." 22 That same year, Russell Barkley

at the Medical College of Wisconsin reviewed the relevant scientific

literature and concluded "the major effect of stimulants appears to

be an improvement in classroom manageability rather than aca¬

demic performance." 28 Next it was James Swanson's turn to weigh

in. The fact that the drugs often left children "isolated, withdrawn

and overfocused” could "impair rather than improve learning," he

said. 29 Carol Whalen, a psychologist from the University of Califor¬

nia at Irvine, noted in 1997 that "especially worrisome has been the

suggestion that the unsalutary effects [of Ritalin] occur in the realm

of complex, high-order cognitive functions such as flexible problem¬

solving or divergent thinking.'" 0 Finally, in 2002, Canadian inves¬

tigators conducted a meta-analysis of the literature, reviewing

fourteen studies involving 1,379 youths that had lasted at least

three months, and they determined that there was "little evidence

for improved academic performance.””

There was one other disappointment with Ritalin. When re¬

searchers looked at whether stimulants improved a child’s behavior

over the long term, they couldn't find any benefit. When a child

stopped taking Ritalin, ADHD behaviors regularly flared up, the

"excitability, impulsivity, or talkativeness" worse than ever. "It is

often disheartening to observe how rapidly behavior deteriorates

when medication is discontinued," Whalen confessed. 32 Nor was

there evidence that staying on a stimulant led to a sustained im¬

provement in behavior. "Teachers and parents should not expect

long-term improvement in academic achievement or reduced anti¬

social behavior," Swanson wrote in 1993." The 1994 edition of the

APA's Textbook of Psychiatry admitted to the same bottom-line

226

ANATOMY OF AN EPIDEMIC

conclusion: "Stimulants do not produce lasting improvements in

aggressivity, conduct disorder, criminality, education achievement,

job functioning, marital relationships, or long-term adjustment." 34

Thirty years of research had failed to provide any good-quality evi¬

dence that stimulants helped "hyperactive” children thrive, and in

the early 1990s, a team of prominent ADHD experts picked to lead

a long-term NIMH study, known as the Multisite Multimodal Treat¬

ment Study of Children with ADHD, acknowledged that this was so.

"The long-term efficacy of stimulant medication has not been

demonstrated for any domain of child functioning,” they wrote. 35

Stimulants Flunk Out

The NIMH touted its ADHD study as "the first major clinical trial”

the institute had ever conducted of "a childhood mental disorder.”

However, it was a rather flawed intellectual exercise right from the

start. Although the investigators, led by Peter Jensen, associate di¬

rector of child and adolescent research at the NIMH, acknowledged

during the planning stages that there was no evidence in the scien¬

tific literature that stimulants improved long-term outcomes, they

did not include a placebo control in the study, reasoning that it

would have been "unethical" to withhold "treatment of known effi¬

cacy” for an extended period. The study basically compared drug

treatment to behavioral therapy, but in that latter group, 20 percent

were on a stimulant at the start of the trial, and there never was a

time during the fourteen months that all of the children in that

group were off such medication. 36

Despite this obvious design flaw, the NIMH-funded investigators

declared victory for the stimulants at the end of fourteen months.

"Carefully crafted medication management" had proven to be "su¬

perior" to behavioral treatment in terms of reducing core ADHD

symptoms. There was also a hint that the medicated children had

fared better on reading tests (although not in other academic sub¬

jects), and as a result, psychiatry now had a long-term study that

documented the continuing benefits of stimulants. "Since ADHD is

THE EPIDEMIC SPREADS TO CHILDREN

227

now regarded by most experts as a chronic disorder, ongoing treat¬

ment often seems necessary,” the researchers concluded. 37

After that initial fourteen-month period of treatment, the investi¬

gators followed up periodically with the students, assessing how

they were doing and whether they were taking an ADHD medica¬

tion. This was now a naturalistic study much like the one that Mar¬

tin Harrow had conducted of schizophrenia outcomes, and readers

of this book, having become familiar with the scientific literature,

can easily guess what is coming next. At the end of three years,

Jensen and the others discovered that "medication use was a signifi¬

cant marker not of beneficial outcome, but of deterioration. That is,

participants using medication in the 24-to-36 month period actually

showed increased symptomatology during that interval relative to

those not taking medication." 38

In other words, those on medications saw their core ADHD symp¬

toms—the impulsiveness, the inattentiveness, the hyperactivity —

worsen, at least in comparison to those not on drugs. In addition,

those on meds had higher "delinquency scores" at the end of three

years, which meant they were more likely to get into trouble in

school and with the police." They were also now shorter and

weighed less than their off-med counterparts, evidence that the

drugs suppressed growth. These results told of a drug therapy

causing long-term harm, and when the NIMH-funded investigators

reported on six-year outcomes, the findings remained the same. Med¬

ication use was "associated with worse hyperactivity-impulsivity and

oppositional defiant disorder symptoms" and with greater "overall

functional impairment." 40

Controversy has long raged over whether ADHD is a "real" dis¬

ease, but this study showed that when it comes to using stimulants to

treat it, the controversy is moot. Even if ADHD is real, stimulants

aren't going to provide long-term help. "We had thought that chil¬

dren medicated longer would have better outcomes. That didn't hap¬

pen to be the case," said William Pelham from the State University of

New York at Buffalo, who was one of the principal investigators.

"There were no beneficial effects, none. In the short term, I medica¬

tion] will help the child behave better, in the long run it won't. And

that information should be made very clear to parents.” 41

228

ANATOMY OF AN EPIDEMIC

Tallying Up the Harm

With any medication, there is a benefit-risk assessment to be made,

and the expectation is that the benefit will outweigh the risks. But in

this case, the NIMH found that over the long term there was noth¬

ing to be entered on the benefit side of the ledger. That leaves only

risks to be tallied up, and so now we need to look at all the ways

that stimulants can harm children.

Ritalin and the other ADHD medications cause a long list of

physical, emotional, and psychiatric adverse effects. The physical

problems include drowsiness, appetite loss, lethargy, insomnia,

headaches, abdominal pain, motor abnormalities, facial and vocal

tics, jaw clenching, skin problems, liver disorders, weight loss,

growth suppression, hypertension, and sudden cardiac death. The

emotional difficulties include depression, apathy, a general dullness,

mood swings, crying jags, irritability, anxiety, and a sense of hostil¬

ity toward the world. The psychiatric problems include obsessive-

compulsive symptoms, mania, paranoia, psychotic episodes, and

hallucinations. Methylphenidate also reduces blood flow and glu¬

cose metabolism in the brain, changes that usually are associated

with "neuropathologic states." 42

Animal studies of stimulants are also cause for alarm. Repeated

exposure to amphetamines, scientists at the Yale School of Medicine

reported in 1999, caused monkeys to exhibit "aberrant behaviors"

that remained long after the drug exposure had stopped. 43 Various

rat studies suggested that lengthy exposure to methylphenidate

might cause dopaminergic pathways to become permanently desen¬

sitized, and since dopamine is the brain's "reward system," med¬

icating the child may produce an adult with a "reduced ability to

experience pleasure.Scientists at Texas Southwestern Medical

Center in Dallas found that "preadolescent” rats exposed to

methylphenidate for fifteen days turned into anxious, depressed

"adult" rats. The adult rats moved around less, were less responsive

to novel environments, and showed a "deficit in sexual behavior.”

They concluded that "administration of methylphenidate” while

THE EPIDEMIC SPREADS TO CHILDREN

229

the brain is still developing "results in aberrant behavioral adapta¬

tions during adulthood." 45

Such is the outcomes literature for Ritalin and other ADHD

medications. The drugs alter a hyperactive child's behavior over the

short term in a manner that teachers and some parents find helpful,

but other than that, the medications diminish a child's life in many

ways, and they may turn a child into an adult with a reduced phys¬

iological capacity to experience joy. And, as we'll see later in this

chapter, there is one other heartbreaking risk with stimulants that

remains to be explored.

Depressing Results

As recently as 1988, the year that Prozac came to market, only one

in 250 children under nineteen years of age in the United States was

taking an antidepressant. 46 That was partly due to a cultural belief

that youth were naturally moody and recovered quickly from de¬

pressive episodes, and partly because study after study had shown

that tricyclics worked no better than placebo in this age group.

"There is no escaping the fact that research studies certainly have

not supported the efficacy of tricyclic antidepressants in treated

depressed adolescents," a Journal of Child and Adolescent Psycho¬

pharmacology editorial acknowledged in 1992. 47

However, when Prozac and other SSRIs were brought to market

and touted as wonder drugs, the prescribing of antidepressants to

children took off. The percentage of children so medicated tripled

between 1988 and 1994, and by 2002 one in every forty children

under nineteen years of age in the United States was taking an anti¬

depressant. 48 Presumably these drugs provide a short-term benefit to

children and adolescents that the tricyclics fail to provide, but unfor¬

tunately, we can't review the scientific literature to see if that is true

because, as is widely acknowledged today, the literature is hopelessly

poisoned. The trials were biased by design; the results that were

published in the scientific journals didn't square with the actual

230

ANATOMY OF AN EPIDEMIC

data; adverse events were downplayed or omitted; and negative

studies went unpublished or were spun into positive ones. "The

story of research into selective serotonin reuptake inhibitor use in

childhood depression is one of confusion, manipulation, and institu¬

tional failure,” the Lancet wrote in a 2004 editorial. The fact that

psychiatrists at leading medical schools had participated in this

scientific fraud constituted an "abuse of the trust patients place in

their physicians." 49

However, a somewhat accurate picture of the merits of the drugs'

efficacy in children has emerged through a roundabout process. Dur¬

ing the course of SSRI-related lawsuits, expert witnesses for the

plaintiffs —most notably David Healy in England and Peter Breggin

in the United States —got a look at some of the trial data, and they

observed that the drugs increased the suicide risk. They spoke out

about what they had found, and with an increasing number of an¬

guished parents telling of how their children had killed themselves

after going on an SSRI, the FDA was forced to hold a hearing in

2004 on this risk. That, in turn, led to a stunning admission by the

FDA's Thomas Laughren about the drugs' efficacy in children.

Twelve of the fifteen pediatric antidepressant trials that had been

conducted had failed. The FDA, in fact, had rejected the applications

of six manufacturers seeking approval to sell their antidepressants to

children. "These are sobering findings," Laughren confessed. 50

The FDA did approve Prozac for use in children, as two of the

three positive studies reviewed by Laughren had come from trials of

this drug. But, as many critics have pointed out, from a scientific

perspective, there is no reason to think that Prozac is any better

than the other SSRIs. The percentage of children who responded to

Prozac in the two positive trials was similar to the drug response

rate in the twelve failed trials; Eli Lilly simply had been better at

using biased trial designs to make it appear that its drug worked.

For example, in one of the two Prozac trials, all of the children were

initially put on placebo for one week, and if they got better during

that period, they were excluded from the study. This helped knock

down the placebo response rate. Next, the children who were ran¬

domized onto Prozac were evaluated for a week, and only those

"who adapted well" to the drug were then enrolled in the study.

THE EPIDEMIC SPREADS TO CHILDREN

231

This helped increase the drug response rate. "Before the study even

started,” explained Jonathan Leo, editor in chief of the journal Eth¬

ical Human Psychology and Psychiatry, "there was a mechanism in

place to maximize any difference between the drug and placebo

groups —the placebo group was preselected for nonresponders,

while the drug group was preselected for responders Yet, even

with this extremely biased trial design, the Prozac-treated children

still fared no better than the placebo group on self-rating scales or

ratings by their parents. In addition, the trial failed to show efficacy

for fluoxetine on its "primary endpoint,” and thus efficacy arose en¬

tirely from a secondary "improvement" scale filled out by the psy¬

chiatrists paid by Eli Lilly to run the trial.

Such was the record of efficacy produced by the SSRIs in pedi¬

atric trials for depression. Most trials failed to show any benefit,

and Eli Lilly had to use a grossly biased trial design to make Prozac

appear effective. In 2003, the Medicines and Healthcare Regulatory

Agency (MHRA) in the United Kingdom essentially banned the use

of SSRIs, except for fluoxetine, in patients under eighteen years old.

English scientists then reviewed all the relevant data and reported in

the Lancet that they supported "the conclusions reached by the

MHRA." 52 The truth, explained the Lancet editors in an accompa¬

nying editorial, was that these drugs "were both ineffective and

harmful in children." 53 Australian scientists chimed in with a simi¬

lar review in the British Medical journal, their article enlivened by

descriptions of the shenanigans that American psychiatrists had

employed to make the SSRIs look beneficial in the first place. The

authors of the positive studies, they said, had "exaggerated the

benefits, downplayed the harms, or both.” The Australians also re¬

viewed Lilly's fluoxetine trials in children and determined that the

"evidence for efficacy is not convincing.” As such, they concluded

that "recommending [any antidepressant] as a treatment option, let

alone as first line treatment, would be inappropriate." 54

In the absence of any efficacy benefit, we are now left with

the unhappy task of tallying up the harm done by the prescribing

of antidepressants to children and teenagers. We can start with

the physical problems. SSRIs may cause insomnia, sexual dysfunc¬

tion, headaches, gastrointestinal problems, dizziness, tremors, ner-

232

ANATOMY OF AN EPIDEMIC

vousness, muscle cramps, muscle weakness, seizures, and a severe

inner agitation known as akathisia, which is associated with an in¬

creased risk of violence and suicide. The psychiatric problems they

can trigger are even more problematic. Timothy Wilens and Joseph

Biederman at Massachusetts General Hospital conducted a chart re¬

view of eighty-two children treated with SSRIs, and determined that

22 percent of the children had suffered an adverse psychiatric event.

Ten percent had become psychotic, and another 6 percent manic.

"One of the most disturbing adverse outcomes is a worsening of

emotional, cognitive or behavioral symptoms,” they wrote. "These

psychiatric adverse events to medication can be significantly impair¬

ing." 55 North Carolina psychiatrist Thomas Gualtieri determined

that 28 percent of the 128 children and adolescents he treated with

SSRIs developed some type of "behavioral toxicity." 56 Other physi¬

cians have told of their SSRI-treated younger patients suffering

panic attacks, anxiety, nervousness, and hallucinations.

Those findings tell of children and adolescents being made sick by

SSRIs, and that is over the short term. To appreciate the long-term

risks, we can look at the problems that have cropped up in adults

and in animal studies. If the children go off the medication, they can

expect to suffer withdrawal symptoms, both physical and mental.

Should they remain on the drugs for years, they are at high risk of

becoming chronically depressed. They may also develop —as the

American Psychiatric Association warns in one of its textbooks —an

"apathy syndrome,” which "is characterized by a loss of motivation,

increased passivity, and often feelings of lethargy and 'flatness.' " S7

There is also memory loss and cognitive decline to worry about, and,

as we saw earlier, animal studies suggest that the drugs may cause

serotonergic neurons to become swollen and misshapen.

Yet Another Illness Appears

First there was the ADHD explosion, and then came the news that

childhood depression was rampant, and not long after that, in the

late 1990s, juvenile bipolar disorder burst into public view. News-

THE EPIDEMIC SPREADS TO CHILDREN

233

papers and magazines ran features on this phenomenon, and once

more psychiatry explained its appearance with a story of scientific

discovery. "It has long been thought in the psychiatric community

that children could not be given a diagnosis of bipolar disorder until

the mid-to-late teens, and that mania in children was extremely

rare,” wrote psychiatrist Demitri Papolos, in his bestselling book

The Bipolar Child. "But scientists in the research vanguard are be¬

ginning to prove that the disorder can begin very early in life and

that it is far more common than was previously supposed." 5 ' Yet

the rise in the number of children and adolescents with this diagno¬

sis was so astonishing —a fortyfold increase from 1995 to 2003 —

that Time, in an article titled "Young and Bipolar," wondered if

something else might be going on. 59 "New awareness of the disor¬

der may not be enough to account for the explosion of juvenile

bipolar cases,” the magazine explained. "Some scientists fear that

there may be something in the environment or in modern lifestyles

that is driving into a bipolar state children and teens who might

otherwise escape the condition." 60

That speculation made perfect sense. How could a severe mental

illness have gone unrecognized for so long, with doctors only now

noticing that thousands of kids were going wildly manic? But if

there were something new in the environment stirring this behavior,

as Time suggested to its readers, there would be a logical explan¬

ation for the epidemic. Infectious agents stir epidemics, and thus, as

we trace the rise of juvenile bipolar disorder, this is what we'll want

to discover: Can we identify "outside agents" that are causing this

modern-day plague?

As we learned earlier, manic-depressive illness was a rare condi¬

tion prior to the psychopharmacology era, affecting perhaps one in

ten thousand people. Although initial onset sometimes occurred

in those fifteen to nineteen years old, it usually didn't appear until

people were in their twenties. But more to the point, it virtually

never appeared in children under thirteen years of age, and both pe¬

diatricians and medical researchers regularly emphasized this point.

In 1945, Charles Bradley said that pediatric mania was so rare

that "it is best to avoid the diagnosis of manic-depressive psycho¬

sis in children." 61 An Ohio physician, Louis Lurie, reviewed the

234

ANATOMY OF AN EPIDEMIC

literature in 1950 and found that "observers have concluded that

mania does not occur in children.'"' Two years later, Barton Hall

reviewed the case histories of 2,200 psychiatric patients five to six¬

teen years old, and found only two instances of manic-depressive ill¬

ness. In both instances, the patients were over thirteen years of age.

"These facts endorse the general belief that manic-depressive states

are illnesses of the maturing or matured personality," Hall said. 6 ' In

1960, Washington University psychiatrist James Anthony scoured

the medical literature for case reports of manic-depressive illness in

children and could find only three. "Occurrence of manic depres¬

sion in early childhood as a clinical phenomenon has yet to be

demonstrated," he wrote. 64

But then, slowly but surely, such case reports began to appear. In

the late 1960s and early 1970s, psychiatrists began prescribing Rit¬

alin to hyperactive children, and suddenly, in 1976, Washington

University's Warren Weinberg, a pediatric neurologist, was writing

in the American journal of Diseases of Childhood that it was time

for the field to realize that children could go manic. "Acceptance of

the concept that mania occurs in children is important in order that

affected children can be identified, the natural history defined, and

appropriate treatment established and offered to these children," he

wrote. 65

This was the moment in the medical literature that pediatric

bipolar disorder was, in essence, "discovered." In his article, Wein¬

berg reviewed the case histories of five children suffering from this

previously unrecognized illness, but he rushed past the fact that at

least three of the five children had been treated with a tricyclic or

Ritalin prior to becoming manic. Two years later, doctors at Massa¬

chusetts General Hospital announced that they had identified nine

children with manic-depressive illness, and they, too, skipped over

the fact that seven of the nine had been previously treated with am¬

phetamines, methylphenidate, or "other medications to affect be¬

havior." 66 Then, in 1982, Michael Strober and Gabrielle Carlson at

the UCLA Neuropsychiatries Institute put a new twist into the juve¬

nile bipolar story. Twelve of the sixty adolescents they had treated

with antidepressants had turned "bipolar" over the course of three

THE EPIDEMIC SPREADS TO CHILDREN

235

years, which —one might think —suggested that the drugs had

caused the mania. Instead, Strober and Carlson reasoned that their

study had shown that antidepressants could be used as a diagnostic

tool. It wasn't that antidepressants were causing some children to

go manic, but rather the drugs were unmasking bipolar illness, as

only children with the disease would suffer this reaction to an anti¬

depressant. "Our data imply that biologic differences between la¬

tent depressive subtypes are already present and detectable during

the period of early adolescence, and that pharmacologic challenge

can serve as one reliable aid in delimiting specific affective syn¬

dromes in juveniles," they said."

The "unmasking" of bipolar illness in children soon speeded up.

The prescribing of Ritalin and antidepressants took off in the late

1980s and early 1990s, and as this occurred, the bipolar epidemic

erupted. The number of hostile, aggressive, and out-of-control chil¬

dren admitted to psychiatric wards soared, and in 1995 Peter

Lewinsohn from the Oregon Research Institute concluded that

1 percent of all American adolescents were now bipolar. 68 Three

years later, Carlson reported that 63 percent of the pediatric pa¬

tients treated at her university hospital suffered from mania, the

very symptom that doctors in the pre-psychopharmacologic era al¬

most never saw in children. "Manic symptoms are the rule, rather

than the exception,” she noted. 69 Indeed, Lewinsohn's epidemiolog¬

ical data was now already out of date. The number of children

discharged from hospitals with a bipolar diagnosis rose fivefold be¬

tween 1996 and 2004, such that this "ferocious mental illness" was

now said to strike one in every fifty prepubertal children in Amer¬

ica. "We don't have the exact numbers yet,” University of Texas

psychiatrist Robert Hirschfeld told Time in 2002, "except we know

it's there, and it's underdiagnosed." 90

An epidemic had come of age, and history reveals that it rose in

lockstep with the prescribing of stimulants and antidepressants to

children.

236

ANATOMY OF AN EPIDEMIC

Creating the Bipolar Child

Given that chronology, we should be able to find data that explains

why stimulants and antidepressants would have that iatrogenic ef¬

fect. There should be data showing that if you treat 5 million chil¬

dren and adolescents with these drugs, then 20 percent or so will

deteriorate in ways that will lead to a bipolar diagnosis. There

should be evidence of iatrogenic harm that adds up mathematically

to an epidemic.

We'll start with Ritalin.

Even before the prescribing of Ritalin took hold, it was well

known that amphetamines could stir psychotic and manic episodes.

Indeed, amphetamines did this with such regularity that psychiatric

researchers pointed to this effect as evidence supporting the dopa¬

mine hypothesis of schizophrenia. Amphetamines upped dopamine

levels in the brain, suggesting that psychosis was caused by too

much of this neurotransmitter. In 1974, David Janowsky, a physi¬

cian at the University of California at San Diego School of Medi¬

cine, tested this hypothesis by giving three dopamine-elevating

agents —d-amphetamine, 1-amphetamine, and methylphenidate —to

his schizophrenia patients. While all three drugs made them more

psychotic, methylphenidate turned out to be tops in this regard,

doubling the severity of their symptoms. 71

Given this understanding of methylphenidate, psychiatry could

expect that giving Ritalin to young children would cause many to suf¬

fer a manic or psychotic episode. Although this risk isn't well quanti¬

fied, Canadian psychiatrists reported in 1999 that nine of ninety-six

ADHD children they treated with stimulants for an average of

twenty-one months developed "psychotic symptoms." 77 In 2006, the

FDA issued a report on this risk. From 2000 to 2005, the agency

had received nearly one thousand reports of stimulant-induced

psychosis and mania in children and adolescents, and given that

these Med Watch reports are thought to represent only 1 percent of

the actual number of adverse events, this suggests that 100,000

youths diagnosed with ADHD suffered psychotic and or manic

episodes during that five-year period. The FDA determined that

THE EPIDEMIC SPREADS TO CHILDREN

237

these episodes regularly occurred in "patients with no identifiable

risk factors" for psychosis, meaning that they were clearly drug-

induced, and that a "substantial portion" of the cases occurred in

children ten years or less. "The predominance in young children of

hallucinations, both visual and tactile, involving insects, snakes and

worms is striking," the FDA wrote. 73

Once this drug-induced psychosis occurs, the children are usually

diagnosed with bipolar disorder. Moreover, this diagnostic progres¬

sion, from medicated ADHD to bipolar illness, is well recognized by

experts in the field. In a study of 195 bipolar children and adoles¬

cents, Demitri Papolos found that 65 percent "had hypomanic,

manic and aggressive reactions to stimulant medications." 74 In

2001, Melissa DelBello, at the University of Cincinnati Medical

Center, reported that twenty-one of thirty-four adolescent patients

hospitalized for mania had been on stimulants "prior to the onset of

an affective episode.” These drugs, she confessed, may "precipitate

depression and/or mania in children who would not have otherwise

developed bipolar disorder." 75

Yet there is an even bigger problem with stimulants. They cause

children to cycle through arousal and dysphoric states on a daily

basis. When a child takes the drug, dopamine levels in the synapse

increase, and this produces an aroused state. The child may show

increased energy, an intensified focus, and hyperalertness. The child

may become anxious, irritable, aggressive, hostile, and unable to

sleep. More extreme arousal symptoms include obsessive-compulsive

and hypomanic behaviors. But when the drug exits the brain,

dopamine levels in the synapse sharply drop, and this may lead to

such dysphoric symptoms as fatigue, lethargy, apathy, social with¬

drawal, and depression. Parents regularly talk of this daily "crash."

But —and this is the key —such arousal and dysphoric symptoms are

the very symptoms that the National Institute of Mental Health

identifies as characteristic of a bipolar child. Symptoms of mania in

children, the NIMH says, include increased energy, intensified goal-

directed activity, insomnia, irritability, agitation, and destructive

outbursts. Symptoms of depression in children include loss of en¬

ergy, social isolation, a loss of interest in activities (apathy), and a

sad mood.

238

ANATOMY OF AN EPIDEMIC

The ADHD to Bipolar Pathway

Stimulant-Induced Symptoms

Bipolar Symptoms

Arousal

Dysphoric

Arousal

Dysphoric

INCREASED ENERGY

SOMNOLENCE

INCREASED ENERGY

SAD MOOD

INTENSIFIED FOCUS

FATIGUE, LEIHARGY

INTENSIFIED GOAL-

LOSS OF ENERGY

HYPERALERTNESS

SOCIAL WITHDRAWAL,

DIRECTED ACIMIY

LOSS OF INTEREST IN

EUPHORIA

AGITATION, ANXIETY

INSOMNIA

IRRITABILITY

HOSimiY

ISOLATION

DECREASED SPONTANEITY

REDUCED CURIOSITY

CONSTRICTION OF AFFECT

DEPRESSION

DECREASED NEED FOR

SLEEP

SEVERE MOOD CHANGE

IRRITABILITY

AGITATION

DESTRUCTIVE OUTBURSTS

ACTIVITIES

SOCIAL ISOLATION

POOR COMMUNI¬

CATION

FEELINGS OF WORTH¬

LESSNESS

HYPOMANIA

EMOTIONAL LABILITY

INCREASED TALKING

UNEXPLAINED

MANIA

DISTRACTTBILITY

CRYING

PSYCHOSIS

HYPOMANIA

MANIA

SIMULANTS USED TO MAT ADHD INDUCE BOTH AROUSAL AND DYSPHORIC SYMPTOMS. THESE DRUG-

INDUCED SYMPTOMS OVERLAP TO A REMARKABLE DEGREE THE SYMPTOMS SAID TO BE CHARACTERISTIC OF

JUVENILE BIPOLAR DISORDER

In short, every child on a stimulant turns a bit bipolar, and the

risk that a child diagnosed with ADHD will move on to a bipolar

diagnosis after being treated with a stimulant has even been quanti¬

fied. Joseph Biederman and his colleagues at Massachusetts General

Hospital reported in 1996 that 15 of 140 children (11 percent) di¬

agnosed with ADHD developed bipolar symptoms —which were

not present at initial diagnosis —within four years.’ 6 This gives us

our first mathematical equation for solving the juvenile bipolar

epidemic: If a society prescribes stimulants to 3.5 million children

and adolescents, as is the case in the United States today, it should

expect that this practice will create 400,000 bipolar youth. As Time

noted, most children with bipolar illness are diagnosed with a

different psychiatric disorder first, with "ADHD the likeliest first

call.”

Now let's look at the SSRIs.

It is well established that antidepressants can induce manic

episodes in adults, and naturally they have this effect on children,

too. As early as 1992, when the prescribing of SSRIs to children was

just getting started. University of Pittsburgh researchers reported

THE EPIDEMIC SPREADS TO CHILDREN

239

that 23 percent of boys eight to nineteen years old treated with

Prozac developed mania or maniclike symptoms, and another 19

percent developed "drug-induced" hostility.” In Eli Lilly's first

study of Prozac for pediatric depression, 6 percent of the children

treated with the drug suffered a manic episode; none in the placebo

group did. 7 ' Luvox, meanwhile, was reported to cause a 4 percent

rate of mania in children under 18. 79 In 2004, Yale University re¬

searchers assessed this risk of antidepressant-induced mania in

young and old, and they found that it is highest in those under

thirteen years of age. 80

The incidence rates cited above are from short-term trials; the

risk rises when children and teenagers stay on antidepressants for

extended periods. In 1995, Harvard psychiatrists determined that

25 percent of children and adolescents diagnosed with depression

convert to bipolar illness within two to four years. "Antidepressant

treatment may well induce switching into mania, rapid cycling or

affective instability in the young, as it almost certainly does in

adults," they explained. 81 Washington University's Barbara Geller

extended the follow-up period to ten years, and in her study, nearly

half of prepubertal children treated for depression ended up bipo¬

lar. 82 These findings give us our second mathematical equation for

solving the bipolar epidemic: If 2 million children and adolescents

are treated with SSRIs for depression, this practice will create

500,000 to 1 million bipolar youth.

We now have numbers that tell of an iatrogenic epidemic:

400,000 bipolar children arriving via the ADHD doorway, and at

least another half million through the antidepressant doorway.

There is also a way that we can double-check that conclusion:

When investigators survey juvenile bipolar patients, do they find

that most traveled down one of those two iatrogenic paths?

Here are the results. In a 2003 study of seventy-nine juvenile

bipolar patients, University of Louisville psychiatrist Rif El-

Mallakh determined that forty-nine (62 percent) had been treated

with a stimulant or an antidepressant prior to their becoming

manic. 83 That same year, Papolos reported that 83 percent of the

195 bipolar children he studied had been diagnosed with some

other psychiatric illness first, and that two-thirds had been exposed

240

ANATOMY OF AN EPIDEMIC

to an antidepressant. 81 Finally, Gianni Faedda found that 84 percent

of the children treated for bipolar illness at the Luci Bini Mood Dis¬

orders Clinic in New York City between 1998 and 2000 had been

previously exposed to psychiatric drugs. "Strikingly, in fewer than

10% [of the cases] was diagnosis of bipolar disorder considered

initially," Faedda wrote. 85

Not surprisingly, parents bear witness to this iatrogenic course.

In May 1999, Martha Hellander, executive director of the Child

and Adolescent Bipolar Foundation, and Tomie Burke, founder of

Parents of Bipolar Children, jointly wrote this letter to the Journal

of the Academy of Child and Adolescent Psychiatry:

Most of our children initially received the ADF1D diagnosis,

were given stimulants and or antidepressants, and either did

not respond or suffered symptoms of mania such as rages,

insomnia, agitation, pressured speech, and the like. In lay lan¬

guage, parents call this "bouncing off the wall.” First hospi¬

talization occurred often among our children during manic or

mixed states (including suicidal gestures and attempts) trig¬

gered or exacerbated by treatment with stimulants, tricyclics,

or serotonin reuptake inhibitors. 86

With so many teenagers prescribed SSRIs, an epidemic of mania

has erupted on college campuses as well. In a 2002 article titled "Cri¬

sis on the Campus," Psychology Today reported that an increasing

number of students, having arrived at college with an antidepres¬

sant prescription in hand, were crashing badly during the school

term. "We are seeing more first episodes of mania every year," said

Morton Silverman, head of counseling services at the University of

Chicago. "It's very disruptive. It generally means hospitalization for

the student.” The magazine was even able to identify a precise date

when this mania epidemic began to emerge: 1988. 81 Readers need

only remember when Prozac came to market to connect the dots.

One final bit of evidence comes from the Netherlands. In 2001,

Dutch psychiatrists reported only thirty-nine cases of pediatric bi¬

polar illness in their country. Dutch investigator Catrien Reichart then

studied the offspring of parents with bipolar disorder in both the

AN EPIDEMIC UNFOLDS

24 2 -

ANATOMY OF AN EPIDEMIC

United States and the Netherlands, and determined that the Ameri¬

cans were ten times more to likely to exhibit bipolar symptoms

before age twenty than the Dutch children. The likely reason for this

difference, Reichart concluded, is that "the prescription of anti¬

depressants and stimulants to children in the U.S. is much higher."”

All of this tells of an epidemic that is mostly iatrogenic in kind.

Fifty years ago, physicians virtually never saw manic-depressive ill¬

ness in preteens, and they rarely diagnosed it in adolescents. Then

pediatricians and psychiatrists began prescribing Ritalin to hyper¬

active children, and suddenly the medical journals began running

case reports of manic children. This problem grew as the prescribing

of Ritalin increased, and then it exploded with the introduction of

the SSRIs. Research then showed that both of these drugs trigger

bipolar symptoms in children and adolescents on a regular basis.

These are the two "outside agents” fueling the epidemic, and it

should be remembered that they do perturb normal brain function.

The manic children showing up at hospital emergency rooms have

dopaminergic and serotonergic pathways that have been altered by

the drugs and are now functioning in an "abnormal" manner. There

is a step-by-step logic that explains this epidemic.

In addition, there are at least three more pathways to a diagnosis

of juvenile bipolar illness. As El-Mallakh, Papolos, and Faedda all

found, there are some children and adolescents so diagnosed who

have no prior exposure to antidepressants or stimulants, and it's

fairly easy to see where the majority of those patients are coming

from. First, Harvard psychiatrist Joseph Biederman led the way in

expanding the diagnostic boundaries in the 1990s, proposing that

extreme "irritability" could be seen as evidence of bipolar illness.

The child no longer needs to have gone manic to be diagnosed as

bipolar. Second, foster children in many states are now regularly

given a bipolar diagnosis, their anger apparently not the result of

having been born into a dysfunctional family, but rather due to a bi¬

ological illness. Finally, teenagers who get into trouble with the law

are now regularly funneled into psychiatric roles. Many states have

set up "mental health courts” that send them off to hospitals and

psychiatric shelters rather than to correctional facilities, and these

youth are adding to the bipolar numbers as well.

THE EPIDEMIC SPREADS TO CHILDREN

243

The Fate That Awaits

As we saw earlier in this book, outcomes for adult bipolar patients

have deteriorated dramatically in the past forty years, and the worst

outcomes are seen in those with "mixed state” and "rapid cycling”

symptoms. That clinical course in adults was virtually never seen

prior to the psychopharmacology era, but rather it was one associ¬

ated with exposure to antidepressants, and, tragically, those are the

very symptoms that afflict the overwhelming majority of juvenile

bipolar patients. They exhibit symptoms "similar to the clinical pic¬

ture reported for severely ill, treatment-resistant adults,” explained

Barbara Geller in 1997. 89

Thus, this is not just a story of children turned bipolar; it's a story

of children afflicted with a particularly severe form of it. Papolos

found that 87 percent of his 195 juvenile bipolar patients suffered

from "ultra, ultra rapid cycling,” which meant that they were con¬

stantly switching between manic and depressed mood states. 99 Simi¬

larly, Faedda determined that 66 percent of the juvenile bipolar

patients treated at the Luci Bini Mood Disorders Clinic were "ultra,

ultra rapid-cyclers," and another 19 percent suffered from rapid cy¬

cling only a little bit less extreme. "In contrast to a biphasic, episodic

and relatively slow cycling course in some adults with bipolar disor¬

der, pediatric forms usually involve mixed mood states and a sub¬

chronic, unstable, and unremitting course," Faedda wrote. 91

Outcome studies have found that the long-term prognosis for

these children is grim. The NIMH, as part of its STEP-BD study,

charted the outcomes of 542 children and adolescent bipolar pa¬

tients, and it reported that pre-adult onset "was associated with

greater rates of comorbid anxiety disorders and substance abuse,

more recurrences, shorter periods of euthymia [normal mood], and

greater likelihood of suicide attempts and violence." 92 Boris

Birmaher, at the University of Pittsburgh, determined that "early

onset" bipolar patients are symptomatic about 60 percent of the

time, and that, on average, they shift "polarity”— from depression

to mania or vice versa —an astonishing sixteen times a year. The

prepubertal patients were "two times less likely than those with

244

ANATOMY OF AN EPIDEMIC

postpubertal onset bipolar to recover," he said, and it was "ex¬

pected that children will be poor responders to treatment when they

become adults." 9 ' DelBello followed a group of adolescents hospi¬

talized for a first bipolar episode and concluded that only 41

percent functionally recovered within a year. 94 This impairment,

Birmaher determined, then worsens after the first year. "Functional

impairment in bipolar appears to increase during adolescence re¬

gardless of age of onset." 95

Youth diagnosed with bipolar illness are typically put on drug

cocktails that include an atypical antipsychotic and a mood stabi¬

lizer. This means that they now have multiple neurotransmitter path¬

ways in their brains that are being mucked up, and naturally, this

treatment does not lead them back to emotional and physical health.

In 2002, DelBello reported that lithium, antidepressants, and mood

stabilizers all failed to help bipolar youth fare better at the end of

two years. Those who were treated with a neuroleptic, she added,

"were significantly less likely to recover than those who did not re¬

ceive a neuroleptic." 96 Six years later, Hayes, Inc., a Pennsylvania

consulting firm that conducts "unbiased” assessments of drugs for

health-care providers, concluded that there was no good scientific

evidence that the mood stabilizers and atypical antipsychotics

prescribed for pediatric bipolar were either safe or effective. "Our

findings indicate that at this time, anticonvulsants and atypical anti¬

psychotics cannot be recommended for children diagnosed with

bipolar disorders," said Elisabeth Houtsmuller, senior analyst for

Hayes. 97 These reports attest to a lack of drug efficacy, but as

Houtsmuller noted, the side effects from these "pharmacological

treatments" are "alarming.” In particular, atypical antipsychotics

may cause metabolic dysfunction, hormonal abnormalities, diabetes,

obesity, emotional blunting, and tardive dyskinesia.* Eventually, the

* In a 2008 report published by the European College of Neuropsychophar¬

macology, Spanish investigators observed that "children and adolescents seem

to have a higher risk than adults for experiencing adverse events such as

extrapyramidal symptoms [movement disorders], prolactin elevation [high

hormone levels], sedation, weight gain, and metabolic effects when taking

antipsychotics." Investigators have also reported that these risks may be higher

for girls than for boys.

THE EPIDEMIC SPREADS TO CHILDREN

245

drugs will induce cognitive decline, and the child who stays on the

cocktails into adulthood can expect to die early as well.

That is the long-term course of this iatrogenic illness: A child

who may be hyperactive or depressed is treated with a drug that

triggers a manic episode or some degree of emotional instability,

and then the child is put on a drug cocktail that leads to a lifetime of

disability.

The Disability Numbers

There are no good studies yet on the percentage of "early onset”

bipolar patients who, when they reach adulthood, end up on the SSI

and SSDI disability rolls. However, the astonishing jump in the

number of "severely mentally ill" children receiving SSI speaks vol¬

umes about the havoc that is being wreaked. There were 16,200

psychiatrically disabled youth under eighteen years old on the SSI

rolls in 1987, and they comprised less than 6 percent of the total

number of disabled children. Twenty years later, there were 561,569

disabled mentally ill children on the SSI rolls, and they comprised

50 percent of the total. This epidemic is even hitting preschool

children. The prescribing of psychotropic drugs to two-year-olds

and three-year-olds began to become more commonplace about a

decade ago, and sure enough, the number of severely mentally ill

children under six years of age receiving SSI has tripled since then,

rising from 22,453 in 2000 to 65,928 in 2007. 98

Moreover, the SSI numbers only begin to hint at the scope of the

harm being done. Everywhere there is evidence of a worsening of

the mental health of children and teenagers. From 1995 to 1999,

psychiatric-related emergency room visits by children increased 59

percent. 99 The deteriorating mental health of the nation's children,

declared U.S. surgeon general David Satcher in 2001, constituted "a

health crisis." 100 Next, colleges were suddenly wondering why so

many of their students were suffering manic episodes or behaving in

disturbed ways; a 2007 survey discovered that one in six college stu¬

dents had deliberately "cut or burned self” in the prior year. 101 All

246

ANATOMY OF AN EPIDEMIC

The Epidemic Hits America's Children

SSI Recipients Under 18 Years Old Disabled by Mental Illness, 1 987-2007

Prior to 1992, the government's SSI reports did not breakdown children recipients into subgroups

by age. Source: Social Security Administration reports, 1987-2007.

of this led the U.S. Government Accountability Office to investigate

what was going on, and it reported in 2008 that one in every fifteen

young adults, eighteen to twenty-six years old, is now "seriously

mentally ill." There are 680,000 in that age group with bipolar dis¬

order and another 800,000 ill with major depression, and, the GAO

noted, this was in fact an undercount of the problem, as it didn't

include young adults who were homeless, incarcerated, or institu¬

tionalized. All of these youth are "functionally impaired" to some

degree, the GAO said. 102

That is where we stand as a nation today. Twenty years ago, our

society began regularly prescribing psychiatric drugs to children

and adolescents, and now one out of every fifteen Americans enters

adulthood with a "serious mental illness." That is proof of the most

tragic sort that our drug-based paradigm of care is doing a great

deal more harm than good. The medicating of children and youth

became commonplace only a short time ago, and already it has put

millions onto a path of lifelong illness.

Suffer the Children

"You wonder all the time:

Are you helping or harming your child?

— jasmine's mom ( 2009 )

There are an endless number of stories of medicated children that

can be told, and as I worked on this book, each visit to a place

where such children can be found —to a family's home or to a foster

care provider or to a psychiatric hospital —offered at least a brief

glimpse of this new society we have created in the past thirty years.

There are, of course, many parents who will tell of how their chil¬

dren have been helped by psychiatric drugs, and given the spectrum

of outcomes that occur with this paradigm of care, that is undoubt¬

edly true (at least over the short term). But this book is about the

epidemic of disabling mental illness that has erupted in our country,

and so the stories that follow tell, at best, of ambivalent long-term

outcomes, and of how diagnosis and treatment during childhood

may lead to a life of disability.

248

ANATOMY OF AN EPIDEMIC

Lost in Seattle

I met the young woman I'll call Jasmine for only a short time, and

even that brief encounter left her visibly agitated.* Born in 1988,

Jasmine resides today in a somewhat dilapidated group home for

the severely mentally ill in a suburb of Seattle, and even as her

mother and I approached the facility, we could see Jasmine through

a window, pacing back and forth. Once we stepped inside, Jasmine

took once glance at me and quickly retreated, huddling next to the

wall, very much liked a frightened creature of the wild. She wore

jeans and a light blue jacket, and she also kept her distance from her

mother —Jasmine won't let anyone hug her now. We drove in two

cars to a nearby Dairy Queen, as Jasmine would not have been will¬

ing to go if I had been in the car with her, and after we got there,

Jasmine stayed in the backseat, staring straight ahead and rocking

back and forth. "If she ever speaks again," her mother says quietly,

"she will have quite the story to tell."

Photos of Jasmine as a young girl are a good place to start her

story. Her mother had shown them to me earlier, and they all told of

a happy childhood. In one, Jasmine is joyfully lined up next to her

two sisters in front of a Disneyland ride; in another, she is showing

off a gap-toothed grin; in a third, she is playfully sticking out her

tongue. "She was very smart and funny, pretty much the light of our

lives," her mother recalls. "She would be outside playing, riding her

bike up and down the street, just like a typical kid. She would even

go around to the neighbors and tell them she would sing 'Row,

Row, Row Your Boat' for fifty cents. She was such a hellion—you

can see in these photos how spunky she was."

All was fine in Jasmine's life until the summer after fifth grade.

Because she still occasionally wet her bed, she was anxious about

going away to camp, and so a doctor prescribed a "bed-wetting"

* Since "Jasmine" could not give consent to having her name used, her mother

and I agreed to keep her identity hidden. I've also kept her mother unnamed

for that same reason.

SUFFER THE CHILDREN

249

pill, which happened to be a tricyclic antidepressant. Very quickly,

Jasmine became agitated and hostile, and one afternoon she told her

mom: "I'm having all these horrible thoughts. I feel like I'm going to

kill people.”

In hindsight, it is easy to see what was happening to Jasmine. Her

extreme agitation was a sign that she was suffering from akathisia,

a side effect of antidepressants closely linked to suicide and vio¬

lence. "But nobody ever asked about whether the drug might have

triggered the homicidal ideation," her mother says. "I didn't learn

that imipramine could do that until years later when I went on the

Internet." Instead, Jasmine was referred to a psychiatrist, who diag¬

nosed her with obsessive-compulsive disorder and bipolar illness.

He put her on a drug cocktail composed of Zoloft, Luvox, and

Zyprexa, and by the time she entered middle school that fall, she

was a changed person.

"It was horrible,” her mother says. "She gained over a hundred

pounds on Zyprexa, and she is petite, five feet, three inches tall.

Kids who knew her from elementary school said, 'What happened

to you?' Boys began calling her 'the beast.' She ended up with no

friends, and she would cry and cry, and ask to eat lunch in the prin¬

cipal's office to stay out of the cafeteria.” Meanwhile, Jasmine’s

rages at home continued, and her psychiatrist upped her dosage of

Zyprexa so high that her eyes would roll up into her head and get

stuck. "It was like she was being tortured. She would lie on her bed

and scream, 'Why is this happening to me?’ "

Eventually, after the Zoloft was finally withdrawn. Jasmine stab¬

ilized fairly well on a combination of Zyprexa and Depakote.

Although she rarely socialized with classmates, she did well academ¬

ically, and during her first years in high school, she regularly earned

A's and kudos for her photography and artwork. She immersed her¬

self in volunteer work, too, helping out at a humane society, a senior

center, and a food bank, her school giving her an "unsung hero”

award for this work. She had come to accept that she was bipolar,

and even made plans to write a book that would help other teenagers

understand it. "She used to tell me, 'Mom, when I graduate from

high school, I am going to stand up and ask, Has anybody ever won¬

dered what happened to me?' She was so brave.”

250

ANATOMY OF AN EPIDEMIC

Toward the end of her junior year, Jasmine read on the Internet

that Zyprexa could cause weight gain, hypoglycemia, and diabetes.

She suffered from the first two of those problems, but when she

asked her psychiatrist about Zyprexa's side effects, he dismissed her

concerns. Enraged, Jasmine "fired” him, and in June of 2005, she

took herself off both medications, stopping them rather abruptly.

Ten days after she took a final dose of Zyprexa, she was on an ex¬

cursion with her mother when she suddenly turned ashen, sweat

beading up on her lip. "This is really bad," she muttered. "Mom,

fight for me.”

Jasmine has been more or less lost to the world ever since. By the

time they arrived at the hospital. Jasmine was screaming and tearing

at her hair. She was deep into a withdrawal psychosis, and doctors

began giving her one powerful drug after another, trying to get it to

abate. "They put her on eleven medications in thirteen days, which

essentially fried her brain,” her mother says. Jasmine began cycling

in and out of hospitals, and every time she was discharged home, it

ended badly. At times, she was so psychotic that she would call the

police to tell them that she was being kidnapped or that men were

building bombs in her front yard. On several occasions, she "es¬

caped” from her house and ran screaming into the streets. Another

time she kicked and punched her mom; afterward, she ripped a soda

can open and slashed at her wrist. "This is the most psychotic per¬

son we have ever seen in the history of this ER," hospital staff told

Jasmine's mom after one such episode.

In late 2006, a doctor put Jasmine on a single antipsychotic,

Clozaril, and that led to a brief respite. Although Jasmine rarely

spoke, she calmed down and entered a school for disabled children.

At night, her mother read to her for hours, seeking to nurture the

spark of sanity she now saw in Jasmine. "I also noticed that if I sang

to her, like to an Alzheimer's patient, she would sing back, commu¬

nicating through singing.” But in early 2007, Jasmine suffered an¬

other severe bout of psychosis, which ended with her screaming in

the middle of a busy road. "There is no hope for her," doctors said,

and soon Jasmine was placed at the residential facility, where today

she passes her days, shying away from contact with other people

and, except for an occasional word now and then, mute.

SUFFER THE CHILDREN

251

"The doctors tell me she was always going to be schizophrenic,”

her mother says. "But no doctor ever asked about this history,

about what she was like before she was put on drugs. And you

know what's so hard to accept? We came in for help that summer

when she was eleven years old for a minor problem that had noth¬

ing to do with psychiatry. In my mind, I can hear her laughing, like

she was back then. But her life has been stolen away. We've lost her,

even though her body remains. I see every minute what I've lost."

Ambivalent in Syracuse

Senior year was a good time for Andrew Stevens. Diagnosed with

ADHD and put on medication when he was in first grade, he'd had

up-and-down times in school until his senior year. But then he took

a course in auto mechanics, and bingo, he excelled in a way he

never had before. "I'm in the zone," he explains. "I enjoy it. It

doesn't feel like school."

On this afternoon, Andrew, who is slight of build and perhaps

five feet, six inches tall, looks very much like the skateboarder he is:

short-cropped hair, black earring, and wearing a T-shirt, shorts, and

tennis shoes splashed with a kaleidoscope of colors. I had met his

mother, Ellen, a year earlier, at a conference in Albany, New York,

and she had expressed a sentiment that, I thought, neatly summar¬

ized the moral aspect of our society's medicating of youth: "Andrew

has been a guinea pig for the medical field," she'd said.

Very early on, she and her husband had realized that Andrew was

different from their other two children. He had speech problems;

his behavior seemed eccentric; he had "rage issues.” In first grade,

he was so wound up he regularly needed to go into the hallway and

bounce on a mini-trampoline in order to refocus. "I remember cry¬

ing when he was diagnosed with ADHD, and it wasn't because my

kid was labeled,” his mother says. "It was, 'Thank God, we know

something real is going on with him and they know how to help

him. It's not our imagination.'

Although she and her husband worried about putting Andrew on

252

ANATOMY OF AN EPIDEMIC

Ritalin, doctors and school authorities led her to believe that she

would be "remiss as a parent" if she didn't give him the medication.

And at first, "it was like a miracle," she says. Andrew's fears abated,

he learned to tie his shoes, and his teachers praised his improved

behavior. But after a few months, the drug no longer seemed to

work so well, and whenever its effects wore off, there would be this

"rebound effect.” Andrew would "behave like a wild man, out of

control.” A doctor increased his dosage, only then it seemed that

Andrew was like a "zombie,” his sense of humor reemerging only

when the drug's effects wore off. Next, Andrew needed to take

clonidine in order to fall asleep at night. The drug treatment didn't

really seem to be helping, and so Ritalin gave way to other stimu¬

lants, including Adderall, Concerta, and dextroamphetamine. "It

was always more drugs," his mother says.

Meanwhile, Andrew's success in the classroom fluctuated accord¬

ing to the talents of his teacher. In fourth and fifth grade, he had

teachers who knew how to work with him, and he did fairly well.

But his sixth-grade teacher was impatient with him, and Andrew's

self-esteem took such a nosedive that his mother homeschooled him

the following year. Andrew's anxieties worsened during this period,

and often he would be "hyperfocused,” worrying all the time that

his mother might die. He also was notably smaller than his peers,

and his parents thought the drugs were probably curbing his

growth. "That has been the most frustrating part. I never know

what is my son and what is the drug," his mother says.

Today, her ambivalence about the medications is such that she

wishes she could turn back the clock and try a different tack. "My

Andrew is not a circle or a square, he is not even a triangle," she ex¬

plains. "He is a rhombus trapezoid, and he will never fit into those

other molds. And I do think that if we had never put him on medi¬

cine, he would have learned many more coping mechanisms, be¬

cause he would have had to. And we should be able to help kids like

Andrew without making them feel so different, without suppressing

their appetite, and without worrying about the long-term effects of

the drugs —all the things I am sitting here worrying about."

When Andrew was younger, he was allowed "medication

breaks" now and then, and when I ask him what that was like, he

SUFFER THE CHILDREN

253

recalls how nice it was to fall asleep without having to take cloni-

dine. Being off meds, he says, "feels less constricted, more free.”

Still, he tells me, he is about to graduate from high school, and he

has ended up at a good place. He has a girlfriend, he enjoys skate¬

boarding and playing the guitar, and thanks to the auto mechanics

class, he now has career plans, as he intends to one day open his

own garage. "It's hard to think back to a time when it could have

been different,” he says, shrugging, thinking about his life on med¬

ications. "I don't think there was a right or wrong choice —this is

just how it's been."

If You're a Ward of the State, You Must Be Bipolar

The medicating of foster children in the United States took off in the

late 1990s, and so I thought, in order to gain a perspective on this

phenomenon, I would visit with Theresa Gately. She and her hus¬

band, Bill, took ninety-six foster children into their Boston home

from 1996 to 2000, and thus she personally witnessed this change

in how our society treats foster kids. The first children that Social

Services sent them weren't medicated, but by the end, "it felt like all

of them were on psych drugs,” she says.

Over the course of several hours, we sat on her front porch,

which looks out over a busy street in a fairly rough part of Boston,

and nearly everyone who walked by waved and affectionately

shouted hello, no matter what their ethnicity. Theresa Gately is a

thin woman with straw blond hair, and she has her own history as

a foster child. Born in 1964, she was sexually abused by her step¬

father, and she turned so defiant as a teenager that she landed in a

Maryland psychiatric hospital. There she was put on Thorazine and

other neuroleptics, and, she said, it wasn't until she started "tongu-

ing" the drugs —pretending to take them while nurses were watch¬

ing and then spitting them out —that her head started to clear.

However, she isn't "anti-medication" at all, and during a difficult

time a few years back, she found an antidepressant and a mood sta¬

bilizer to be extremely helpful, and she remains on those drugs.

254

ANATOMY OF AN EPIDEMIC

As a foster mother, Gately was required to follow "medical ad¬

vice" and give psychiatric medications to the children who arrived

on them. Most of the children were on cocktails, and it seemed to

her that the drugs were primarily being used to make the children

quieter and easier to manage. "One young girl, Liz, was so heavily

medicated that she couldn't think at all," she recalls. "You would

ask her if she wanted a pork chop and she wouldn't answer.” An¬

other was "almost mute when she came to me. The last thing you

need to do is give somebody who already doesn't talk more drugs."

Theresa ran through the histories of several more of her foster chil¬

dren, concluding that "maybe nine to eleven [of the ninety-six chil¬

dren] needed to have the drugs and were being helped.”

She has kept track of a number of the ninety-six children, and as

could be expected, many have struggled mightily as adults. Had she,

I wondered, noticed a difference in the fate of those who stayed on

the drug cocktails, versus those who stopped taking them?

"When I look back on the kids that stayed on the drugs and those

who got off, it is the ones that are off that are the successes," she

says. "Liz should never have been on the drugs. She got off the drugs

and is doing great. She is a full-time student in nursing school and al¬

most ready to graduate, and is about to get married. The thing is, if

you get off the drugs, you start building these coping mechanisms.

You learn internal controls. You start building these strengths. Most

of these kids have had very bad stuff happen to them. But they are

able to rise above their past once they are off the medications, and

then they can move on. The kids who were drugged and continue to

be drugged never have that opportunity to build coping skills. And

because they never had that opportunity as a teenager, as an adult

they don't know what to do with themselves.”

Hers isn't a scientific study. But her experience does offer a peek

into the toll that the medicating of foster kids is taking. Most of those

who stayed on the drugs, she says, ended up "filing for disability.”

Like Theresa Gately, Sam Clayborn, who is a social worker in New

Rochelle, New York, can tell from personal experience what it is

like to have been a foster kid in the United States. When he was

SUFFER THE CHILDREN

255

born in Harlem in 1965, his mother was unable to take care of him,

and by age six he was living in a residential group home. We met in

his apartment in Croton-on-Hudson, and very quickly he put things

into a historical context. "They weren't so hot on psychiatric diag¬

noses back then," he explains. "They were more into beating your

ass, restraining you, and just throwing you into an empty fucking

room. I'm glad I grew up when it was like that rather than what it is

like today, because if I grew up now, I'd be fucking drugged up. I'd

be doped out and zonked out.”

For the past two decades, he and his partner Eva Dech have

worked as advocates for foster children and poor youth in West¬

chester County. She also had a tough childhood, which included a

stint in a mental hospital where she was forcibly medicated, and

they see a racial aspect to this medicating of foster children. Starting

around 2000, rates of black youth diagnosed with bipolar disorder

soared, and based on hospital discharges, they are now said to suf¬

fer from bipolar disorder at a greater rate than whites. 1 The diagno¬

sis provides a rationale for medicating the kids, and that in turn

puts yet one more burden on them, Clayborn believes.

"The Tuskegee syphilis experiments were nothing compared to

this. That's mild shit compared to what they are doing to black kids

today. The pharmaceutical companies and the government are fuck¬

ing in cahoots, and they are doing a wicked dance with a lot of peo¬

ple's lives. They don't give a fuck about these kids. It's all about

capitalism, and they will sacrifice all the niggers in the hood. We are

damaging these kids for life, and the majority of these kids will

never rebound. These kids will be destroyed and they are going to

make the SSI rolls more overwhelmed."

One of the area youth that Clayborn has mentored is Jonathan

Barrow, who had been splayed out on the living room floor during

our conversation, half sleeping and half listening. Born in 1985 in

Harlem to a mother on crack, Jonathan bounced around as a child,

eventually ending up at his grandfather's home in White Plains. At

age seven, he was diagnosed with ADHD and put on Ritalin. In ju¬

nior high, he started becoming rebellious and got into a few fights,

and that led to a diagnosis of bipolar disorder and a prescription for

Depakote and Risperdal. Up until that time, Jonathan had been an

256

ANATOMY OF AN EPIDEMIC

active adolescent who spent most of his free time on the basketball

court, but now he began spending most of his time "in his room iso¬

lated," Clayborn says. He went onto the SSI disability rolls before

he turned eighteen, apparently "severely impaired” by this bipolar

illness, and he remains on SSI today. "I'm doped up," Jonathan ex¬

plains, still somewhat heavy-lidded from his afternoon nap. "I don't

like it. It makes me sleepy and feel like a dope fiend.”

At this, Clayborn rose from his chair, more agitated than ever.

"This is happening to a lot of the brothers today, and once they are

on the medication, it takes them away from themselves. They lose

all the willpower to struggle, to change, to make something out of

themselves and have success. They succumb to the chemical hand¬

cuffs of the motherfucking medications. It's medical bondage is

what it is."

Not long after that interview, I attended a meeting of the Statewide

Youth Advisory Council at Westborough State Hospital in Massa¬

chusetts. The council is composed of young adults who entered the

mental health system before they were eighteen, and it provides ad¬

vice to the Massachusetts Department of Mental Health on what it

can do to help teenagers with psychiatric problems thrive as adults.

In 2008, the coordinator of the council was Mathew McWade, who

was first diagnosed when he was in the seventh grade, and it was he

who made my visit possible.

At the meeting, I went around the table and asked everyone how

they had gotten into the system. I thought I might hear stories of

kids who were first put on a stimulant or an antidepressant and then

moved on to a bipolar diagnosis, and while there was some of that,

several men in this racially mixed group told of yet another societal

route to psychiatric disability.

When Cal Jones* was sixteen years old, he had gotten into a

violent argument that ended with his being treated in the emergency

room at Children's Hospital in Boston. There he told ER staff that

* Cal Jones is a pseudonym. Hospital staff asked that I not reveal the names of

the hospitalized patients.

SUFFER THE CHILDREN

257

he "wanted to kill the other kid," a sentiment that earned him a trip

to a psychiatric facility, where he was diagnosed with bipolar ill¬

ness. "They didn't run any tests," he says. "They just asked me a

bunch of questions and started me on a bunch of medicines.” Since

then, he has been hospitalized twenty-five times. He doesn't like

antipsychotics, and so he regularly stops taking them when he is dis¬

charged, preferring to smoke marijuana instead, and inevitably that

leads to trouble. "I get arrested and get sent back to the (psych) hos¬

pital, and I'm like okay, it's just a business. The more patients they

have, the more the doctors make. But I hate it. I can't stand it. I feel

like a slave in a Nazi camp.”

At least three others at the meeting told similar stories. One

young man said that shortly after he graduated from high school in

2002 , he got upset over a family matter and smashed the windows

of his car. "I was having a bad time. They wanted to label me as

mentally ill. I don't know if I am.” Another explained that six

months earlier, after he had committed a minor criminal act, a judge

had given him the choice of going to prison or to Westborough State

Hospital. "It's safer in here than in prison,” he says, explaining his

choice. A third member of the council said that he had been diag¬

nosed with bipolar illness at age thirteen after "I killed somebody.”

Their stories bore witness to another pathway into the mental

health system for poor youth. Delinquency and crime can get them

diagnosed, medicated, and routed into a mental institution. While

many of the young men on the council were on heavy-duty cock¬

tails, moving about and speaking in a sluggish manner, the one who

had told of having killed somebody was now living in the commu¬

nity and not taking any medications. "If the state really wants to

help us, it should put money into a jobs program,” he says.

Back to Syracuse

As a last stop, I returned to visit the two Syracuse families —Jason

and Kelley Smith and Sean and Gwen Oates —that I had met in the

spring of 2008. Families, friends, therapists, and doctors had given

258

ANATOMY OF AN EPIDEMIC

the two families conflicting advice about whether they should medi¬

cate their child, and faced with such bewildering advice, the two

families had come to opposite decisions.

Jessica

I knew from an earlier telephone conversation that Jessica Smith

had been doing well, and when I arrived at their home, she bounded

to the door to welcome me, much as she had a year earlier. When

she was diagnosed with bipolar disorder at age four, her parents had

rejected the recommendations of staff at the State University of

New York Health Sciences Center that she be put on a cocktail of

three drugs that included an antipsychotic. Today, they have an

eight-year-old girl reminiscent of Maurice Sendak's endearing

"Really Rosie” character on their hands. Jessica, who is very much

the extroverted child, had recently starred in a school musical. "She

just loves it,” her father says, and he pointed to her behavior on

opening night as evidence of how much better she had become at

controlling her emotions. "She was playing a brainiac, and another

girl in the show stole her chair, which she wasn't supposed to do.

We could see that Jessica was upset. But then she let it pass. It

showed that she is getting better at de-escalating situations.”

Although Jessica no longer sees a therapist, "there are still strug¬

gles," her mother says. "She still has a hard time with groups, with

playing with more than one kid at a time. And she will still lash out

if someone hurts her feelings. She wants to be the boss, and she can

be loud and boisterous. But the kicking and biting is gone.”

Adds her father: "She has a big personality, but that is like others

in my family. I was the same way. I was very loud. I wouldn't sit

still. And I turned out all right."

Nathan

Nathan Oates had gone through a more topsy-turvy twelve months.

I had called his mother several times during the year, and in the

summer of 2008, Nathan —who had been diagnosed with ADHD at

age four and subsequently with bipolar illness —had been doing

SUFFER THE CHILDREN

259

well. He took Concerta for the ADHD and Risperdal for the bipolar

disorder, and that summer he discovered that he "loves track,” his

mother told me. "They are teaching him how to do hurdles and the

long jump.” Even more important, his mood swings had become

less severe, his hostility toward his sister had lessened, and he was

sleeping better, too. "He said he wants to start being more responsi¬

ble,” his mother said. "He gets up in the morning and makes his

bed, and now he is at a point he will take a shower by himself. He is

starting to do things without my hounding him. It seems he is kind

of maturing on his own."

This was a heartening report, but that relatively peaceful time

ended when Nathan returned to school in the fall. He became quite

anxious and moody, and started resisting going to school. The

physician's assistant overseeing his care upped his Risperdal, hoping

that would quiet his anxiety. "They are trying to figure out whether

his anxiety is bipolar related or a separate disorder,” his mother ex¬

plained, in a phone interview in early 2009. "The ADHD is fine and

under control. If this doesn't work, they will give him an anti¬

anxiety medication. They want to make sure that he doesn't get too

lethargic under the higher dose of Risperdal.”

When I returned to Syracuse in the spring, Nathan's parents were

close to despair over the difficulties that he was experiencing.

Nathan's anxiety hadn't abated, and to make matters worse, he had

lost control of his bladder. A few days earlier, his mother had wit¬

nessed in heartbreaking fashion how this was affecting her son. "I

went to pick him up in school, and he was sitting in the middle of

the room at his desk alone," she says. "It was almost like he was in¬

visible to everybody else. The teachers swear he has friends but he

never talks about anybody. There is only one classmate who doesn't

pick on him." This isolation, his mother adds, followed Nathan

into the home. "He stays in his room all the time.”

Nathan's father remained hopeful that another "medication

adjustment” would help his son. But beyond that, both parents con¬

fessed that they were at a loss about what to do. The psychologist

who counseled Nathan was running out of ideas; the school wasn't

doing much to alleviate Nathan's severe anxiety; and their families

and friends didn't appreciate how difficult this all was. "I feel so

26 o

ANATOMY OF AN EPIDEMIC

alone in this," his mother says. "It stinks. It's wearing. It's exhaust¬

ing. I cry for him. I just don't know what to do anymore. I don't

know how to help him.”

Before I left, Nathan came down from his room, and he shyly

showed me a few of his favorite possessions, including a Star Wars

helmet. He told me that Zachariah was his best friend (the one

classmate who didn't tease him), and then he taught me how to fold

a piece of paper into an airplane, which he sent flying around the

room. "I like to make movies" with a video recorder, he says, and

eventually I quizzed him on a couple of subjects he loves. "The

Titanic sank in 1912,” he informs me, and after that he proudly

identified various bones in the human body —he is fascinated with

drawings of skeletons. "His teachers all love him,” his mother says,

and at that moment, it was very easy to see why.

part four

Explication of a Delusion

The Rise of an Ideology

"It was not surprising that medical students accepted

the dogma of biomedical reductionism in psychiatry

uncritically; they had no time to read and analyze the

original literature. What took me a while to understand,

as I moved through my residency, was that psychiatrists

rarely do the critical reading either."

-COLIN ROSS, CLINICAL ASSOCIATE PROFESSOR OF

PSYCHIATRY AT SOUTHWEST MEDICAL CENTER IN

DALLAS, TEXAS (1 995)'

We have investigated the epidemic of mental illness that has erupted

in the United States during the past fifty years in a step-by-step fash¬

ion, and having reviewed the outcomes literature for each of the

major disorders, there is an obvious next question to address. Why

does our society believe that a "psychopharmacological revolution"

has taken place during the past fifty years, when the scientific litera¬

ture so clearly shows that the revolution failed to materialize? Or, to

put it another way, what is the source of our remarkable societal

delusion?

To answer that, we need to trace the rise of "biological psychia¬

try" and then look at the stories that psychiatry —once it embraced

that belief system —came to tell.

Psychiatry's Season of Discontent

During the heady days of the 1950s, when it seemed that a new

breakthrough drug was being discovered every year, psychiatry had

reason to be optimistic about its future. It now had magic pills like

264

ANATOMY OF AN EPIDEMIC

the rest of medicine, and once NIMH researchers and others ad¬

vanced the chemical imbalance theory of mental disorders, it

seemed that these pills might indeed be antidotes to physical dis¬

eases. "American psychiatry," exclaimed former NIMH director

Gerald Klerman, "accepted psychopharmacology as its domain." 2

But two decades later, those heady days were long gone, and psychi¬

atry was mired in a deep crisis, beleaguered on so many fronts that

it worried about its survival. There was a sense, said American Psy¬

chiatric Association (APA) director Melvin Sabshin in 1980, that

the "profession is under severe siege and is cut off from allies." 3

The first problem that had arisen for psychiatry was an intellec¬

tual challenge to its legitimacy, an attack launched in 1961 by

Thomas Szasz, a psychiatrist at the State University of New York in

Syracuse. In his book The Myth of Mental Illness, he argued that

psychiatric disorders weren't medical in kind, but rather labels ap¬

plied to people who struggled with "problems in living” or simply

behaved in socially deviant ways. Psychiatrists, he said, had more in

common with ministers and police than they did with physicians.

Szasz's criticism rattled the field, since even mainstream publica¬

tions like the Atlantic and Science found his argument to be both

cogent and important, the latter concluding that his treatise was

"enormously courageous and highly informative . . . bold and often

brilliant." 4 As Szasz later told the New York Times, "In smoke-filled

rooms, time and time again. I've heard the view that Szasz has killed

psychiatry. I hope so." 5

His book helped launch an "antipsychiatry" movement, and

other academics in the United States and Europe —Michel Foucault,

R. D. Laing, David Cooper, and Erving Goffman, just to name a

few—joined the fray. All questioned the "medical model” of mental

disorders and suggested that madness could be a "sane” reaction to

an oppressive society. Mental hospitals might better be described as

facilities for social control, rather than for healing, a viewpoint

crystallized and popularized in One Flew Over the Cuckoo's Nest,

which swept the Oscars for 1975. Nurse Ratched was the malevo¬

lent cop in that movie, which ended with Randle McMurphy

(played by Jack Nicholson) being lobotomized for failing to stay in

line.

THE RISE OF AN IDEOLOGY

265

The second problem that psychiatry faced was a growing compe¬

tition for patients. In the 1960s and 1970s, a therapy industry

blossomed in the United States. Thousands of psychologists and

counselors began offering services to the "neurotic" patients that

psychiatry had laid claim to ever since Freud had brought his couch

to America. By 1975, the nonphysician therapists outnumbered the

shrinks in the United States, and with benzodiazepines falling out of

favor, the neurotic patients who had been content to pop "happy

pills" in the 1960s were embracing primal scream therapy, Esalen

retreats, and any number of other "alternative” therapies said to

help heal the wounded soul. Partly as a result of this competition,

the median earnings of a U.S. psychiatrist in the late 1970s were

only $70,600, and while this was a good wage at the time, it still

put psychiatry near the bottom of the medical profession. "Non¬

psychiatric mental health professionals are laying claim to some, or

even all, of psychiatry's task domains,” wrote Tufts University psy¬

chiatrist David Adler. There was reason, he said, to worry about the

"death of psychiatry." 6

Internal divisions also ran deep. Although the field had turned

toward biological psychiatry after the arrival of Thorazine, with

most psychiatrists eager to speak well of the drugs, the Freudians

who dominated many medical schools in the 1950s had never com¬

pletely climbed on that bandwagon. While they found some use for

the drugs, they still conceived of most disorders as psychological in

kind. As such, during the 1970s, there was a deep philosophical

split between the Freudians and those who embraced a "medical

model” of psychiatric disorders. In addition, there was a third fac¬

tion in the field, composed of "social psychiatrists." This group

thought that psychosis and emotional distress often arose from an

individual's conflict with his or her environment. If that was so, al¬

tering that environment or creating a supportive new one —as Loren

Mosher had done with his Soteria Project —would be a good way to

help a person heal. Like the Freudians, the social psychiatrists did

not see drugs as the centerpiece of care, but rather as agents that

were sometimes helpful and sometimes not. With these three

approaches in conflict, the field was suffering from an "identity cri¬

sis," Sabshin said. 7

266

ANATOMY OF AN EPIDEMIC

By the end of the 1970s, the leaders of the APA regularly spoke of

how their field was in a fight for "survival.” In the 1950s, psychia¬

try had become the fastest growing specialty in medicine, but during

the 1970s, the percentage of medical school graduates choosing to

go into it dropped from 11 percent to less than 4 percent. This lack

of interest in the field, the New York Times reported in an article

titled "Psychiatry's Anxious Years," was "seen as a particularly

painful indictment." 8

Avoiding the Obvious

Such was psychiatry's self-assessment in the 1970s. It looked into

the mirror and saw the field under attack by an "antipsychiatry"

movement, threatened economically by nonphysician therapists,

and split by internal disagreements. But, in fact, it was turning a

blind eye to the root problem, which was that its medications were

failing in the marketplace. This was what had allowed the crisis to

take hold and spread.

If the first generation of psychotropics had truly worked, the

public would have been pounding on psychiatrists' doors seeking

prescriptions for these medicines. Szasz's argument that mental ill¬

ness was a "myth" might have been seen by some as intellectually

interesting, worthy of debate in academic circles, but it wouldn't

have curtailed the public's appetite for drugs that made them feel

and function better. Similarly, psychiatry could have brushed off the

competition from psychologists and counselors as a harmless nui¬

sance. Depressed and anxious people might have indulged in

screaming therapies and mud baths, and sought out talk therapy

from psychologists, but the prescription bottles would have re¬

mained in their medicine cabinets. Nor would the internal divisions

have persisted. If the pills had proved to provide long-term relief,

then all of psychiatry would have embraced the medical model, for

the other proffered forms of care —psychoanalysis and nurturing

environments —would have been perceived as too labor-intensive

THE RISE OF AN IDEOLOGY

267

and unnecessary. Psychiatry fell into a crisis during the 1970s be¬

cause the "miracle pill” aura around its drugs had disappeared.

From the moment that Thorazine and the neuroleptics were in¬

troduced into asylum medicine, many hospitalized patients had

found them objectionable, so much so that many "tongued” the

pills. This practice was so pervasive that Smith, Kline and French, in

the early 1960s, developed a liquid Thorazine, which the patients

could be made to swallow. Other manufacturers developed in¬

jectable forms of their neuroleptics so that hospitalized patients

could be forcibly medicated. "Warning!" an ad for liquid Thorazine

screamed. "Mental Patients Are Notorious DRUG EVADERS." 9 In

the early 1970s, patients who had experienced such forced treat¬

ment began forming groups with names such as the "Insane Libera¬

tion Front" and the "Network Against Psychiatric Assault." At

their rallies, many carried signs that read hugs, not drugs!

One Flew Over the Cuckoo's Nest helped legitimatize that

protest in the public's mind, and that movie appeared shortly after

psychiatry suffered the embarrassment of news reports that the

Soviet Union was using neuroleptics to torture dissidents. These

drugs apparently inflicted such physical pain that quite sane people

would recant their criticisms of a Communist government rather

than endure repeated doses of Haldol. Dissident writings told of

psychiatric drugs that turned people into "vegetables," the New

York Times concluding that this practice could be seen as "spiritual

murder." 10 Then, in 1975, when Indiana senator Birch Bayh

launched an investigation of the use of neuroleptics in juvenile insti¬

tutions, ex-mental patients hijacked the public hearing to testify

that the drugs caused "excruciating pain" and had turned them into

emotional "zombies." Antipsychotics, said one ex-patient, "are used

not to heal or help, but to torture and control. It is that simple.” 11

These drugs were no longer being presented to the public as

agents that made a raving madman "sit up and talk sense," as Time

had reported in 1954, and even as this new view of antipsychotics

was sinking into the public mind, the benzodiazepines fell into dis¬

repute. The federal government classified them as schedule IV

drugs, and soon Edward Kennedy was announcing that benzos

268

ANATOMY OF AN EPIDEMIC

had "produced a nightmare of dependence and addiction." 12 Anti-

psychotics and the benzodiazepines were the two classes of drugs

that had launched the psychopharmacology revolution, and with

both now seen by the public in a negative light, sales of psychiatric

drugs plunged in the 1970s, from 223 million drugstore prescrip¬

tions in 1973 to 153 million in 1980. 13 In its article on psychiatry's

"anxious years," the New York Titties explained that a primary rea¬

son that medical school graduates were avoiding the field was

because its treatments were perceived to be "low in efficacy."

This was a topic that psychiatry did not like to talk about or ac¬

knowledge. Yet, at the same time, everyone understood what gave

psychiatrists a competitive advantage in the therapy marketplace.

New Jersey psychiatrist Arthur Piatt was at a professional meeting

in the late 1970s when a keynote speaker laid it out for them: "He

said, 'What is going to save us is that we're physicians,' " Piatt re¬

calls. 14 They could write prescriptions and the psychologists and

social workers couldn't, and that was an economic landscape that

presented the field with an obvious solution. If the image of psy¬

chotropic drugs could be rehabilitated, psychiatry would thrive.

Putting on the White Coat

The process that led to the rehabilitation of psychiatric drugs in the

public's mind got under way in the 1970s. Threatened by Szasz's

criticism that psychiatrists did not really function as "doctors," the

APA argued that psychiatrists needed to more explicitly embrace

this role. "A vigorous effort to remedicalize psychiatry should be

strongly supported,” said the APA's Sabshin in 1977. 15 Numerous

articles appeared in the American Journal of Psychiatry and other

journals explaining what this meant. "The medical model,” wrote

University of Kentucky psychiatrist Arnold Ludwig, is based on the

"premise that the primary identity of the psychiatrist is as a physi¬

cian." 16 Mental disorders, said Paul Blaney, from the University of

Texas, were to be seen as "organic diseases." 17 The psychiatrist's

focus should be on making the proper diagnosis, which arose from

THE RISE OF AN IDEOLOGY

269

a cataloguing of the "symptoms and signs of illness," said Samuel

Guze, from Washington University. It was only psychiatrists, he

added, that had the "medical training necessary for the optimal ap¬

plication of the most effective treatments available today for psychi¬

atric patients: psychoactive drugs and ECT [electroshock]." 18

Theirs was a model of care straight out of internal medicine. The

doctor in that setting took a patient's temperature, or tested blood

glucose levels, or did some other diagnostic test, and then once the

illness was identified, prescribed the appropriate drug. "Remedical-

ization" of psychiatry meant that the Freudian couch was to be trot¬

ted off to the Dumpster, and once that happened, psychiatry could

expect to see its public image restored. "The medical model is most

strongly linked in the popular mind to scientific truth,” explained

Tufts University psychiatrist David Adler. 19

In 1974, the APA picked Robert Spitzer from Columbia Univer¬

sity to head up the task force that would, through a revision of the

APA’s Diagnostic and Statistical Manual, prompt psychiatrists to

treat patients in this way. DSM-II, which had been published in

1967, reflected Freudian notions of "neurosis," and Spitzer and

others argued that such diagnostic categories were notoriously "un¬

reliable.” He was joined by four other biologically oriented psychi¬

atrists on the task force, including Samuel Guze at Washington

University. DSM-III, Spitzer promised, would serve as "a defense of

the medical model as applied to psychiatric problems."” The man¬

ual, said APA president Jack Weinberg in 1977, would "clarify to

anyone who may be in doubt that we regard psychiatry as a spe¬

cialty of medicine." 21

Three years later, Spitzer and his colleagues published their hand¬

iwork. DSM-III identified 265 disorders, all of which were said to

be distinct in kind. More than one hundred psychiatrists had con¬

tributed to the five-hundred-page tome, authorship that indicated it

represented the collective wisdom of American psychiatry. To make

a DSM-III diagnosis, a psychiatrist would determine if a patient had

the requisite number of symptoms said to be characteristic of the

disease. For instance, there were nine symptoms common to "major

depressive episode,” and if five were present, then a diagnosis of this

illness could be made. The new manual, Spitzer boasted, had been

270

ANATOMY OF AN EPIDEMIC

"field tested," and those trials had proven that clinicians in different

facilities, when faced with the same patient, were likely to arrive at

the same diagnosis, proof that diagnosis would no longer be as sub¬

jective as before. "These [reliability] results were so much better

than we had expected” they would be, he said. 22

Psychiatry now had its medical-model "bible," and the APA and

others in the field rushed to extol it. DSM-III is an "amazing docu¬

ment ... a brilliant tour de force," Sabshin said. 23 "The develop¬

ment of DSM-III,” said Gerald Klerman, "represents a fateful point

in the history of the American psychiatric profession . . . [and] its

use represents a reaffirmation on the part of American psychiatry to

its medical identity and its commitment to scientific medicine." 24

Thanks to DSM-III, wrote Columbia University psychiatrist Jerrold

Maxmen, "the ascendance of scientific psychiatry became offi¬

cial . . . the old [psychoanalytical] psychiatry derives from theory,

the new psychiatry from fact." 25

But as critics at the time noted, it was difficult to understand why

this manual should be regarded as a great scientific achievement.

No scientific discoveries had led to this reconfiguring of psychiatric

diagnoses. The biology of mental disorders remained unknown, and

the authors of DSM-III even confessed that this was so. Most of the

diagnoses, they said, "have not yet been fully validated by data

about such important correlates as clinical course, outcome, family

history, and treatment response." 26 It was also evident that the

boundary lines between disease and no disease had been arbitrarily

drawn. Why did it require the presence of five of nine symptoms

said to be characteristic of depression for a diagnosis of the illness

to be made? Why not six such symptoms? Or four? DSM-III, wrote

Theodore Blau, president of the American Psychological Associa¬

tion, was more of "a political position paper for the American

Psychiatric Association than a scientifically-based classification

system." 22

None of that mattered, however. With the publication of DSM-

III, psychiatry had publicly donned a white coat. The Freudians had

been vanquished, the concept of neurosis basically tossed into the

trash bin, and everyone in the profession was now expected to em¬

brace the medical model. "It is time to state forcefully that the

THE RISE OF AN IDEOLOGY

271

identity crisis is over," Sabshin said. 28 Indeed, the American Journal

of Psychiatry urged its members to "speak with a united voice, not

only to secure support, but to buttress [psychiatry's] position

against the numerous other mental health professionals seeking pa¬

tients and prestige." 29 The medical model and DSM-III, observed

University of Tennessee psychiatrist Ben Bursten in 1981, had been

used to "rally the troops ... to thwart the attackers [and] to rout

the enemy within." 30

Indeed, it wasn't only the Freudians who had been vanquished.

Loren Mosher and his band of social psychiatrists also had been

roundly defeated and sent packing.

When Mosher started his Soteria Project in 1971, everyone un¬

derstood that it threatened the "medical model” theory of psychi¬

atric disorders. Newly diagnosed schizophrenia patients were being

treated in an ordinary home, staffed by nonprofessionals, without

drugs. Their outcomes were to be compared with patients treated

with drugs in a hospital setting. If the Soteria patients fared better,

what would that say about psychiatry and its therapies? From the

minute that Mosher proposed it, the leaders of American psychiatry

had tried to make sure it would fail. Although Mosher headed up

the Center for Schizophrenia Studies at the NIMH, he'd still needed

to obtain funding for Soteria from the grants committee that over¬

saw NIMH's extramural research program, which was composed of

psychiatrists from leading medical schools, and that committee

slashed his initial request of $700,000 for five years to $150,000 for

two years. This ensured that the project would struggle with fin¬

ances from the outset, and then, in the mid-1970s, when Mosher

began reporting good results for his Soteria patients, the committee

struck back. The study had "serious flaws” in its design, it said.

Evidence that Soteria patients had superior outcomes was "not

compelling." 31 Mosher must be biased, the academic psychiatrists

concluded, and they demanded that Mosher be removed as the pri¬

mary investigator. "The message was clear,” Mosher said, in an in¬

terview twenty-five years later. "If we were getting outcomes this

good, then I must not be an honest scientist." 32 Soon after that, the

grants committee shut off funding for the experiment altogether,

and Mosher was pushed from his job at the NIMH, even though the

272

ANATOMY OF AN EPIDEMIC

committee had grudgingly concluded, in its final review of the proj¬

ect, that "this project has probably demonstrated that a flexible, com¬

munity based, non-drug residential psychosocial program manned

by non-professional staff can do as well as a more conventional

community mental health program.”

The NIMH never funded an experiment of this type again.

Furthermore, Mosher's ouster provided everyone in the field with a

clear message: Those who did not get behind the biomedical model

would not have much of a future.

Psychiatry's Mad Men

Once DSM-III was published, the APA set out to market its "med¬

ical model" to the public. Although professional medical organiza¬

tions have always sought to advance the economic interests of their

members, this was the first time that a professional organization so

thoroughly adopted the marketing practices familiar to any com¬

mercial trade association. In 1981, the APA established a "division

of publications and marketing” to "deepen the medical identifica¬

tion of psychiatrists," and in very short order, the APA transformed

itself into a very effective marketing machine. 3 ' "It is the task of the

APA to protect the earning power of psychiatrists," said APA vice

president Paul Fink in 1986. 34

As a first step, the APA established its own press in 1981, which

was expected to bring "psychiatry's best talent and current knowl¬

edge before the reading public." 35 The press was soon publishing

more than thirty books a year, with Sabshin happily noting in 1983

that the books "will provide much positive public education about

the profession." 36 The APA also set up committees to review the

textbooks it published, intent on making sure that authors stayed

on message. Indeed, in 1986, as it readied publication of Treatment

of Psychiatric Disorders, the APA's Roger Peele —one of the or¬

ganization's elected officials —worried anew about this concern.

"How do we organize 32,000 members for advocacy?" he asked.

"Who should be allowed to speak to the issue of the treatment of

THE RISE OF AN IDEOLOGY

273

psychiatric illness? Only researchers? Only the academic elite? . . .

Only members appointed by APA presidents?" 37

Very early on, the APA realized that it would be valuable to de¬

velop a nationwide roster of "experts" that could promote the

medical-model story to the media. It established a "public affairs in¬

stitute” to oversee this effort, which involved training members "in

techniques for dealing with radio and television." In 1985 alone, the

APA ran nine "How to Survive a Television Interview” workshops. 3 '

Meanwhile, every district branch in the country identified "public

affairs representatives" who could be called on to speak to the

press. "We now have an experienced network of trained lead¬

ers who can effectively cope with all varieties of media,” Sabshin

said. 39

Much like any commercial organization selling a product, the

APA regularly courted the press and exulted when it received posi¬

tive coverage. In December 1980, it held a daylong media confer¬

ence on "new advances in psychiatry" that "was attended by

representatives of some of the nation's most prestigious and widely

circulated newspapers," Sabshin crowed. 40 Next, it placed "public

service spots" on television to tell its story, an effort that included

sponsoring a two-hour program on cable television titled Your

Mental Health. It also developed "fact sheets” for distribution to

the media that told of the prevalence of mental disorders and the

effectiveness of psychiatric drugs. Harvey Rubin, chair of the APA's

public affairs committee, taped a popular radio program that car¬

ried the medical-model message to listeners around the country. 41

The APA had launched an all-out media blitz —it handed out

awards to journalists whose stories it liked —and every year Sabshin

detailed the good publicity this effort was generating. In 1983, he

noted that "with the help and urging of the Division of Public

Affairs, U.S. News and World Report published a major cover story

on depression, which included substantial quotes from prominent

psychiatrists." 42 Two years later, Sabshin announced that "APA

spokespersons were placed on the Phil Donahue program, Nightline

and other network programs." That same year, it "helped develop a

Reader's Digest book chapter on mental health." 43

All of this paid big dividends. Newspaper and magazine head-

274

ANATOMY OF AN EPIDEMIC

lines now regularly told of a "revolution" under way in psychiatry.

Readers of the New York Times learned that "human depression is

linked to genes" and that scientists were uncovering the "biology of

fear and anxiety." Researchers, the paper reported, had discovered

"a chemical key to depression.Societal belief in biological psy¬

chiatry was clearly taking hold, just as the APA hoped, and in 1984,

Jon Franklin of the Baltimore Evening Sun wrote a seven-part series

titled "The Mind-Fixers" on the astonishing advances that were

being made in the field. 45 Fie put this revolution into a historical

context:

Since the days of Sigmund Freud the practice of psychiatry

has been more art than science. Surrounded by an aura of

witchcraft, proceeding on impression and hunch, often inef¬

fective, it was the bumbling and sometimes humorous

stepchild of modern science. But for a decade and more, re¬

search psychiatrists have been working quietly in laborato¬

ries, dissecting the brains of mice and men and teasing out the

chemical formulas that unlock the secrets of the mind. Now,

in the 1980s, their work is paying off. They are rapidly iden¬

tifying the interlocking molecules that produce human

thought and emotion. ... As a result, psychiatry today stands

on the threshold of becoming an exact science, as precise and

quantifiable as molecular genetics. Ahead lies an era of psy¬

chic engineering, and the development of specialized drugs

and therapies to heal sick minds.

Franklin, who interviewed more than fifty leading psychiatrists

for his series, called this new science "molecular psychiatry," which

was "capable of curing the mental diseases that afflict perhaps 20

percent of the population." Fie was awarded the Pulitzer Prize for

expository journalism for this work.

Books written by psychiatrists for the lay press at this time told a

similar story. In The Good News About Depression, Yale University

psychiatrist Mark Gold informed readers that "we who work in this

new field call our science biopsychiatry, the new medicine of the

mind. ... It returns psychiatry to the medical model, incorporating

THE RISE OF AN IDEOLOGY

275

all the latest advances in scientific research, and for the first time in

history, providing a systematic method of diagnosis, treatment, cure

and even prevention of mental suffering.” In the past few years,

Gold added, psychiatry had conducted "some of the most incredible

medical research ever done. . . . We have probed the frontiers of

science and human understanding wherein lie the ultimate compre¬

hension and cure of all mental illnesses.” 46

If there was one book that cemented this belief in the public's

mind, it was The Broken Brain. Published in 1984 and written by

Nancy Andreasen, future editor of the American journal of Psychi¬

atry, it was touted as "the first comprehensive account of the bio¬

medical revolution in the diagnosis and treatment of mental

illness.” In it, Andreasen concisely set forth the tenets of biological

psychiatry: "The major psychiatric illnesses are diseases. They

should be considered medical illnesses just as diabetes, heart dis¬

ease, and cancer are. The emphasis in this model is on carefully di¬

agnosing each specific illness from which the patient suffers, just as

an internist or neurologist would." 47

The broken brain— hers was a book with a brilliant title, one that

conveyed a bottom-line message that the public could easily grasp

and remember. However, what most readers failed to notice was

that Andreasen, in several places in her book, confessed that re¬

searchers had not yet actually found that people diagnosed with

psychiatric disorders have broken brains. Researchers had new

tools for investigating brain function, and they hoped this knowl¬

edge would come. "Nevertheless, the spirit of a revolution —the

sense that we are going to change things dramatically, even if the

process requires a number of years —is very much present," An¬

dreasen explained. 46

Twenty-five years later, that breakthrough moment still lies in the

future. The biological underpinnings of schizophrenia, depression,

and bipolar disorder remain unknown. But the public has long since

been convinced otherwise, and we can see now the marketing

process that got this delusion under way. At the start of the 1980s,

psychiatry was worried about its future. Sales of psychiatric drugs

had notably declined in the past seven years, and few medical

school graduates wanted to go into the field. In response, the APA

276

ANATOMY OF AN EPIDEMIC

mounted a sophisticated marketing campaign to sell its medical

model to the public, and a few years later the public could only gasp

in awe at the apparent advances that were being made. A revolution

was under way, psychiatrists were now "mind-fixers,” and as a

Johns Hopkins "brain chemist,” Michael Kuhar, told Jon Franklin,

this "explosion of new knowledge” was going to lead to new drugs

and broad changes in society that would be "fantastic!" 49

Four-Part Harmony

Psychiatrists were not the only ones in American society who were

eager to tell of a biomedical revolution in psychiatry. During the

1980s, a powerful coalition of voices came together to tell this story,

and this was a group with financial clout, intellectual prestige, and

moral authority. Together they enjoyed all the resources and social

status necessary to convince the public of almost anything, and this

storytelling coalition has stayed intact ever since.

As we saw earlier, the financial interests of pharmaceutical

companies and physicians became closely aligned in 1951, when

Congress gave doctors their monopolistic prescribing privileges. But

in the 1980s, the APA and the industry took this relationship one

step further and essentially entered into a drug marketing "partner¬

ship." The APA and psychiatrists at academic medical centers

served as the front men in this arrangement, the public thereby see¬

ing "men of science” on stage, while the pharmaceutical companies

quietly provided the funds for this capitalistic enterprise.

The seed for this partnership was planted in 1974 when the APA

formed a task force to assess the importance of pharmaceutical sup¬

port for its future. The answer was "very," and in 1980 that led the

APA to institute a policy change of transformative importance. Up

to that time, pharmaceutical companies had regularly put up fancy

exhibits at the APA's annual meeting and paid for social events, but

they hadn't been allowed to put on "scientific” talks. However, in

1980, the APA's board of directors voted to allow pharmaceutical

companies to start sponsoring scientific symposiums at its annual

THE RISE OF AN IDEOLOGY

277

meeting. The drug firms paid the APA a fee for this privilege, and

soon the most well-attended events at its annual meeting were the

industry-funded symposiums, which provided the attendees a sump¬

tuous meal and featured presentations by a "panel of experts." The

speakers were paid handsomely to give the talks, and the drug com¬

panies made certain that their presentations went off without a

hitch. "These symposia are meticulously prepared with rehearsals

before the meeting, and they have excellent audio-visual content,"

Sabshin explained. 50

The door to a full-fledged "partnership" had been flung open, one

that would sell the medical model and the benefits of psychiatric

medications to the public, and the APA now began to regularly rely

on pharmaceutical money to fund many of its activities. The drug

companies began "endowing” continuing education programs and

psychiatric grand rounds at hospitals, and, as one psychiatrist ob¬

served, the companies were "happy to cap them with free food and

booze to sweeten the love of learning." 51 When the APA launched a

political action committee in 1982 to lobby Congress, this effort was

funded by pharma. The industry helped pay for the APA's media¬

training workshops. In 1985, APA secretary Fred Gottlieb observed

that the APA was now receiving "millions of dollars of drug house

money" each year. 50 Two years later, an issue of the APA's newsletter,

Psychiatric News, featured a photo of Smith, Kline and French

handing a check to APA president Robert Pasnau, which led one

reader to quip that the APA had become the "American Psychophar-

maceutical Association." 53 The APA was prospering financially now,

with its revenues jumping from $10.5 million in 1980 to $21.4 mil¬

lion in 1987, and it settled into a fancy new building in Washington,

D.C. It openly talked about "our partners in industry." 54

For the drug companies, the best part of this new partnership was

that it enabled them to turn psychiatrists at top medical schools into

"speakers,” even while those doctors considered themselves "inde¬

pendent.” The paid-for symposiums at the annual meetings greased

this new relationship. The symposiums were said to be "educational”

presentations, with the drug companies promising not to "control"

what the experts said. Yet their presentations were rehearsed,

and every speaker knew that if he broke from that script and started

2y8

ANATOMY OF AN EPIDEMIC

talking about the drawbacks of psychiatric medications, he would

not be invited back.* There would be no industry-sponsored

symposiums on "supersensitivity psychosis," or the addictive effects

of benzodiazepines, or how antidepressants were no more effective

than active placebo. These speakers came to be known as "thought

leaders," their presence on the symposium panels elevating them to

the status of "stars" in the field, and by the early 2000s, they were

getting paid $2,000 to $10,000 per speech. "Some of us," confessed

E. Fuller Torrey, "believe that the present system is approaching a

high-class form of prostitution." 55

• These "thought leaders" also became the experts regularly

quoted by the media, and they wrote the textbooks published by the

APA. Psychiatry's thought leaders shaped our society's understand¬

ing of mental disorders, and once they began serving as paid speak¬

ers, the pharmaceutical companies sent money their way through

multiple channels. As the New England Journal of Medicine ob¬

served in 2000, thought leaders "serve as consultants to companies

whose products they are studying, join advisory boards and speak¬

ers' bureaus, enter into patent and royalty arrangements, agree to

be the listed authors of articles ghostwritten by interested compa¬

nies, promote drugs and devices at company-sponsored sympo¬

siums, and allow themselves to be plied with expensive gifts and

trips to luxurious settings." 55 Nor was it just a few psychiatrists

from academia that pharma courted with its dollars. The drug in¬

dustry understood this was a very effective way to market their

drugs, and collectively the companies began paying money to

virtually every well-known figure in the field. In 2000, when the

New England Journal of Medicine tried to find an expert to write an

* The academic psychiatrists also began to regularly give dinner talks to local

psychiatric groups, and in 2000, University of Mississippi psychiatrist John

Norton confessed in a letter to the New England Journal of Medicine that after

he wrote about the side effects of the sponsor's drug, "my invitations to speak

suddenly dropped from four to six times per month to essentially none." Prior

to that experience, he said, "I deluded myself into thinking I was educating

physicians, and not being swayed by the sponsors."

THE RISE OF AN IDEOLOGY

279

editorial on depression, it "found very few who did not have finan¬

cial ties to drug companies that make antidepressants.”

The NIMH also joined this storytelling coalition. The biological

psychiatrists knew that they had successfully captured the NIMH

when the Soteria Project was closed and Mosher was ousted, and

during the 1980s the NIMH actively promoted the biological psy¬

chiatry story to the public, an effort that took wing under the leader¬

ship of Shervert Frazier. Prior to being picked to head the NIMH in

1984, Frazier directed the APA's Commission on Public Affairs,

which had run the media-training workshops underwritten by phar¬

maceutical firms, and soon Frazier was announcing that the NIMH,

for the first time in its forty-year history, would launch a major ed¬

ucational campaign called the Depression Awareness, Recognition

and Treatment (DART) program. This educational effort would in¬

form the public that depressive disorders are "common, serious and

treatable," the NIMH said. Pharmaceutical companies would "con¬

tribute resources, knowledge and other forms of assistance to the

project,” which the NIMH promised would run for at least a

decade.” As it helped expand the market for psychiatric medica¬

tions, the NIMH even assured the public that the broken-brain

story was true. "Two decades of research have shown that [psychi¬

atric disorders] are diseases and illnesses like any other diseases and

illnesses," said NIMH director Lewis Judd in 1990, even though

nobody had ever been able to explain the nature of the pathology.”

The final group to participate in this storytelling campaign was

the National Alliance for the Mentally 111. Founded in 1979 by two

Wisconsin women, Beverly Young and Harriet Shelter, it arose as a

grassroots protest to Freudian theories that blamed schizophrenia

on "aloof, uncaring mothers and preoccupied mothers who were

unable to bond with their infants," a NAMI historian observed.”

NAMI was eager to embrace an ideology of a different kind, and

the message it sought to spread, said former NAMI president Agnes

Hatfield in 1991, was that "mental illness is not a mental health

problem; it is a biological illness. There is considerable clarity on

the part of families that they are focusing on a physical disease." 60

For the APA and pharma companies, the emergence of NAMI

could not have come at a more opportune moment. This was a

28 o

ANATOMY OF AN EPIDEMIC

parents' group eager to embrace biological psychiatry, and both the

APA and pharmaceutical firms pounced. In 1983, the APA "entered

into an agreement with NAMI" to write a pamphlet on neuroleptic

drugs, and soon the APA was encouraging its branches across the

country "to foster collaborations with local chapters of the National

Alliance for the Mentally 111." 61 The APA and NAMI joined together

to lobby Congress to increase funding for biomedical research, and

the beneficiary of that effort, the NIMH —which saw its research

budget soar 84 percent during the 1980s —thanked the parents for

it. "The NIMH in a very meaningful sense is NAMI's institute,"

Judd told NAMI president Laurie Flynn in a 1990 letter. 62 By that

time, NAMI had more than 125,000 members, most of whom were

middle-class, and it was busily seeking to "educate the media, public

officials, healthcare providers, educators, the business community,

and the general public about the true nature of brain disorders," said

one NAMI leader. 6 ' NAMI brought a powerful moral authority to

the telling of the broken-brain story, and naturally pharmaceutical

companies were eager to fund its educational programs, with eigh¬

teen firms giving NAMI $11.72 million from 1996 to 1999. 64

In short, a powerful quartet of voices came together during the

1980s eager to inform the public that mental disorders were brain

diseases. Pharmaceutical companies provided the financial muscle.

The APA and psychiatrists at top medical schools conferred intellec¬

tual legitimacy upon the enterprise. The NIMH put the govern¬

ment's stamp of approval on the story. NAMI provided a moral

authority. This was a coalition that could convince American soci¬

ety of almost anything, and even better for the coalition, there was

one other voice on the scene that, in its own way, helped make the

story bulletproof in society's eyes.

The Critics Believe in Aliens

The story of a "psychopharmacology revolution" had first been

told in the 1950s and 1960s, and then, as we've seen in this chapter,

it was revived in the 1980s. However, the storytellers in the 1980s

THE RISE OF AN

D E O L O G Y

281

were more vulnerable to criticism than the storytellers of the earlier

decades simply because there was now twenty years of research that

undermined their narrative. None of the drugs had proven to help

people function well over the long term, and the chemical-

imbalance theory of mental disorders was in the process of flaming

out. As NIMH researchers had concluded in 1984, "elevations or

decrements in the functioning of serotonergic systems per se are not

likely to be associated with depression.” Close readers of The Bro¬

ken Brain could also see that, in fact, no great new discoveries had

been made. There was a Grand Canyon-sized gap between what the

broken-brain storytellers were intimating was true and what was

actually known, and that same gap would appear in their stories

when Prozac and the other second-generation drugs came to mar¬

ket. But fortunately for the proponents of biological psychiatry, crit¬

icism of the medical model and of psychiatric drugs became

associated, in the public mind, with Scientology.

L. Ron Hubbard, a science-fiction writer, founded the Church of

Scientology in 1952. One of the church's core tenets is that the earth

is populated by souls that previously lived on other planets, an "ex¬

traterrestrial” creation myth that could have been lifted directly

from a sci-fi novel. In addition, Hubbard had his own ideas about

how to heal the mind. Prior to founding Scientology, he had pub¬

lished Dianetics: The Modern Science of Mental Health, which out¬

lined the use of an "auditing” process to eliminate painful past

experiences from the mind. The scientific and medical community

ridiculed dianetics as quackery and dismissed Hubbard as a huck¬

ster, and he in turn developed an intense hatred for psychiatry. In

1969, Scientology and Thomas Szasz cofounded the Citizens Com¬

mission on Human Rights, and this group began waging campaigns

against lobotomy, electroshock, and psychiatric drugs.

This proved to be very fortuitous for the APA and its storytelling

partners as they raised the flag of biological psychiatry. Indeed, it is

easy to imagine the drug companies deciding to secretly fund Scien¬

tology's protests, eager as they were to shove money to any organ¬

ization that would —wittingly or unwittingly— advance their cause.

For not only did Scientologists believe in extraterrestrials, they also

had gained a reputation for being a secretive, litigious, and even

282

ANATOMY OF AN EPIDEMIC

malevolent cult. Scientology, Time wrote in 1991, is a "hugely

profitable global racket that survives by intimidating members and

critics in a Mafia-like manner." 65 Thanks to Scientology, the powers

that be in psychiatry had the perfect storytelling foil, for they could

now publicly dismiss criticism of the medical model and psychiatric

drugs with a wave of the hand, deriding it as nonsense that arose

from people who were members of a deeply unpopular cult, rather

than criticism that arose from their own research. As such, the pres¬

ence of Scientology in the storytelling mix served to taint all

criticism of the medical model and psychiatric drugs, no matter

what its source.

Those were the storytelling forces that formed in the 1980s.

When Prozac arrived on the market, they were lined up perfectly for

the creation —and maintenance —of a tale about psychiatry's great

new leap.

The Story That Was . . . and

Wasn’t Told

When it comes to dead bodies in current psychotropic

trials, there are a greater number of them in the

active treatment groups than in the placebo groups.

This is quite different from what happens in pencillin

trials or trials of drugs that really work."

-DAVID HEALY, PROFESSOR OF PSYCHIATRY AT

CARDIFF UNIVERSITY, WALES (2008)

During the 1920s, owners of radios in the heartland of America reg¬

ularly tuned into station KFKB, which had perhaps the most power¬

ful signal in the country at that time, even though it emanated from

tiny Milford, Kansas. "This is Dr. John R. Brinkley greeting his

friends in Kansas and everywhere," they'd hear, and Dr. Brinkley

did indeed have a most amazing story to tell. In 1918, he had begun

transplanting goat gonads into the testicles of older men worried

about their declining virility, a fifteen-minute operation, he told

KFKB listeners, that had been proven to "completely restore" sex¬

ual prowess. "A man is as old as his glands," the good doctor

would explain, and this rejuvenating surgery worked because the

goat tissue "blends with and nourishes the human tissue, stimulat¬

ing the human gland to new activity." 2

Although Brinkley's medical credentials were of a dubious sort —

he had a degree from Eclectic Medical University of Kansas City, a

diploma mill —he was a masterful storyteller and something of an

advertising genius. After his first few operations, he told his story to

newspapers in Kansas, and soon they were publishing pictures of

him cradling the first "goat-gland baby," the offspring of an older

man who had undergone the operation. Older men began pouring

284

ANATOMY OF AN EPIDEMIC

into Milford, each paying $750 for the procedure, and Brinkley

cranked up his publicity machine. He hired three press agents to

write ready-to-print newspaper features, which were then distrib¬

uted to "publications interested in popularizing the latest develop¬

ments from the laboratories of science.” Naturally, these planted

articles included testimonials from satisfied customers, such as J. J.

Tobias, chancellor of Chicago Law School, who —the articles said —

liked to pound his chest and shout: "I'm a new man! It's one of the

great things of the century!” Brinkley established his own "Scien¬

tific Press" and reported a ”90% to 95% success rate” for his sur¬

gery, which, he explained, returned the body to a proper hormonal

"balance.” Once he began broadcasting his story on KFKB in 1923,

he became so famous that three thousand letters arrived at his Mil¬

ford hospital each day, and by the late 1920s, he was perhaps the

wealthiest "doctor" in the United States.

Eventually, Dr. Brinkley earned a place in medical history as one

of the great charlatans of all time, when the American Medical As¬

sociation targeted him as a quack. But when it came to marketing

his goat-gonad surgery, he employed advertising techniques and a

storytelling model that have stood the test of time. He published ar¬

ticles that appeared scientific, courted the press, claimed a very high

success rate, offered a biological rationale for why the surgery

worked, and provided reporters with quotes from satisfied cus¬

tomers. That —as Eli Lilly and other drug manufacturers can attest —

is a tried-and-true formula for turning a psychiatric drug into a

commercial success.

Fibs, Lies, and a Blockbuster Drug

Today, the fraudulent nature of the story told by Eli Lilly and psy¬

chiatry about Prozac when it came to market is fairly well known,

having been documented by Peter Breggin, David Healy, and Joseph

Glenmullen, among others. Breggin and Healy wrote their accounts

after gaining access to Eli Lilly files while serving as expert witnesses

in civil lawsuits, which allowed them to see data and internal

THE STORY THAT WAS

AND WASN'T TOLD

285

memorandums that belied what the public had been told about the

drug. At the risk of going over familiar ground, we need to revisit

that story briefly, for it will help us see, with considerable clarity,

how our societal delusions about the merits of the "second-

generation" psychiatric drugs were formed. Eli Lilly's marketing of

Prozac proved to be a model that other companies followed as they

brought their drugs to market, and it involved telling a false story in

the scientific literature, hyping that story even more to the media,

and hiding risks that could lead to disability and death for those

who used the drugs.

The science of fluoxetine

Drug development begins in the laboratory, with investigation into

a drug's "mechanism of action,” and as we learned earlier, Eli Lilly

scientists determind in the mid-1970s that fluoxetine caused sero¬

tonin to "pile up” in the synapse, which in turn triggered a series of

physiological changes in the brain. Next, in animal studies, the drug

was found to cause stereotyped activity in rats (repetitious sniffing,

licking, etc.) and aggressive behavior in cats and dogs. 3 In 1977, Eli

conducted its first small trial in humans, but "none of the eight pa¬

tients who completed the four-week treatment showed distinct

drug-induced improvement," Eli Lilly's Ray Fuller tolcb his col¬

leagues in 1978. The drug also had caused "a fairly large number of

reports of adverse reactions.” One patient had gone psychotic on

the drug, and others had suffered from "akathisia and restlessness,"

Fuller said. 1

The trials of fluoxetine had barely begun and it was clear that Eli

Lilly had a big problem. Fluoxetine didn't appear to lift depression

and it caused a side effect —akathisia —known to increase the risk of

suicide and violence. After more reports of this kind came in, Eli

Lilly amended its trial protocols. "In future studies, the use of ben¬

zodiazepines to control the agitation will be permitted,” Fuller

wrote on July 23, 1979. 5 The benzodiazepines would help suppress

reports of akathisia, and likely boost efficacy results, as several trials

of benzodiazepines for depression had shown them to be as effective

as a tricyclic. Of course, as Eli Lilly's Dorothy Dobbs later confessed

286

ANATOMY OF AN EPIDEMIC

in court, the use of benzodiazepines was "scientifically bad,” as it

would "confound the results" and "interfere with the analysis of

both safety and efficacy," but it enabled the company to continue

development of fluoxetine. 6

Still, even with addition of the benzodiazepines, fluoxetine failed

to perform well. During the early 1980s, the company conducted a

phase III trial of the drug in Germany, and in 1985, the German li¬

censing authority, Bundesgesundheitsamt (BGA), concluded that

this drug was "totally unsuitable for the treatment of depression." 7

According to the patients' "self ratings" (as opposed to the doctors'

ratings), the drug produced "little response or no improvement in

the clinical picture of the patients," the BGA noted. 8 At the same

time, it had caused psychosis and hallucinations, and increased

some patients' anxiety, agitation, and insomnia, "which as adverse

effects exceed those which are considered acceptable by medical

standards," the BGA wrote. 9 Most problematic of all, this drug

treatment could prove fatal. "Sixteen suicide attempts were made,

two of these with success," the BGA said. 19 A German Eli Lilly em¬

ployee privately calculated that the incidence rate of suicidal acts

for the fluoxetine patients was ”5.6 times higher than under the

other active medication, imipramine." 11

With Germany having rejected its application, Eli Lilly naturally

worried that it would be unable to gain FDA approval for fluoxe¬

tine.* It needed to hide the suicide data, and'in a 1994 civil lawsuit,

Nancy Lord, an expert in clinical trial design, explained how the

company did it. First, Eli Lilly instructed investigators to record var¬

ious drug-related adverse events as "symptoms of depression." As

such, in the trial results submitted to the FDA, the problems were

attributed to the disease rather than to fluoxetine. Second, when Eli

Lilly scientists tabulated the data from case report forms, they

changed individual reports of "suicidal ideation" to "depression."

Third, Lilly employees went through the German data "and pulled

out [suicide] cases that they didn't think were suicide." 12

All of these shenanigans, Lord told a court in 1994, made the

* At the end of 1989, Eli Lilly obtained approval to market fluoxetine in

Germany, but with a label that warned of the elevated risk of suicide.

THE STORY THAT WAS

AND WASN'T TOLD

287

entire testing process scientifically "worthless.” Yet even with these

statistical manipulations, Eli Lilly still struggled to present a con¬

vincing case for fluoxetine in its application to the FDA. It had

conducted placebo-controlled trials at eight sites, and in four of

them, the fluoxetine patients had fared no better than the placebo

group, and in the others, fluoxetine was only slightly better than a

placebo." Meanwhile, when Peter Breggin reviewed Lilly's docu¬

ments, he discovered that imipramine had proven to be more effec¬

tive than fluoxetine in six of seven trials. 14 The FDA, in its March

28, 1985, review of one large trial, made the same observation:

"Imipramine was clearly more effective than placebo, whereas flu¬

oxetine was less consistently better than placebo." 15 At best, fluoxe¬

tine's efficacy was of a very marginal sort, and FDA reviewer

Richard Kapit also worried about its safety. At least thirty-nine pa¬

tients treated with fluoxetine had gone psychotic in the short trials,

and slightly more than 1 percent had become manic or hypomanic.

Other side effects included insomnia, nervousness, confusion, dizzi¬

ness, memory dysfunction, tremors, and impaired motor coordina¬

tion. Fluoxetine, Kapit concluded, "may negatively affect patients

with depression." 16 The FDA also understood that Eli Lilly had

tried to hide many of these problems, the company having engaged

in "large-scale underreporting” of the harm that fluoxetine could

cause, according to reviewer David Graham. 17

While the trials may have been scientifically worthless, they

nevertheless proved to be an accurate forecast of what happened

after Prozac was brought to market. There were numerous anec¬

dotal accounts of Prozac-treated patients committing horrendous

crimes or killing themselves, and so many adverse-events reports

flowed into the FDA's MedWatch program that Prozac quickly be¬

came America's most complained about drug. By the summer of

1997, the FDA had received thirty-nine thousand such reports

about Prozac, far outstripping the number received by any other

drug for that nine-year period (1988-1997). The MedWatch filings

told of hundreds of suicides, and of a long list of vexing side effects,

which included psychotic depression, mania, abnormal thinking,

hallucinations, hostility, confusion, amnesia, convulsions, tremors,

and sexual dysfunction." The FDA estimates that only 1 percent of

288

ANATOMY OF AN EPIDEMIC

all adverse events are reported to Med Watch, which suggests that

roughly 4 million Americans during that nine-year period had a bad

or even fatal reaction to Prozac. 19

The story told in the medical journals

Obviously, the record chalked up by fluoxetine in the clinical trials

was not one that would support a successful launch in the market¬

place. The public was not likely to embrace a medication that

German's licensing authority, in its initial review, had deemed "to¬

tally unsuitable" as a treatment for depression. If Prozac was going

to be successful, the psychiatrists that Eli Lilly had paid to run the

trials needed to tell a very different story in the medical journals and

to the public.

The first account of a U.S. trial of fluoxetine appeared in the

journal of Clinical Psychiatry in 1984. This novel agent, wrote

James Bremner, from Northwest Psychopharmacology Research in

Washington, "provides effective antidepressant activity with fewer

and less troublesome side effects than imipramine. . . . None of the

adverse events reported by fluoxetine patients were considered to be

drug related." Fluoxetine, he added, "proved more effective than

the tricyclic antidepressant." 211 Next, John Feigner, from the Univer¬

sity of California at San Diego, reported that fluoxetine was at least

equal in efficacy to imipramine (and probably superior to the tri¬

cyclic) and that "no serious side effects were observed” in his

twenty-two fluoxetine patients during a five-week study. 21 A theme

had been sounded —a very safe and improved antidepressant had

been developed —and Eli Lilly's investigators stuck to it in the years

that followed. "Fluoxetine was better tolerated than imipramine,"

California psychiatrist Jay Cohn reported in 1985. 22 "This drug,"

said Eli Lilly's Joachim Wernicke, in another article in the Journal of

Clinical Psychiatry, "has very few serious side effects." 2 ' Finally, in

the 1985 report on its large phase III trial, Eli Lilly announced that

"fluoxetine produced greater improvement than placebo on all

major efficacy parameters." 21

While these reports did tell of a new drug that was superior to the

old class of antidepressants, this still was not a narrative of a

THE STORY THAT WAS

AND WASN’T TOLD

289

"breakthrough" medication. There was no sense of why this drug

worked better, but as FDA approval for fluoxetine neared, a new

"fact" began to appear in the scientific reports. In a 1987 article in

the British Journal of Psychiatry, Sidney Levine wrote that "studies

have shown that [serotonin] deficiency plays an important role in

the psychobiology of depressive illness." 25 While this was not what

had actually been found —Levine had apparently missed the 1984

NIMH report that "elevations or decrements in the functioning of

serotonergic systems per se are not likely to be associated with de¬

pression”—this article set the stage for fluoxetine to be touted as a

drug that fixed a chemical imbalance. Two years later, University of

Louisville psychiatrists surveyed the fluoxetine literature in order to

provide "prescribing guidelines for the newest antidepressant," and

they wrote that "depressed patients have lower than normal con¬

centrations of [serotonin metabolites] in their cerebrospinal fluid.”

A delusional belief was now spreading through the medical litera¬

ture, and perhaps not surprisingly, the Kentucky psychiatrists con¬

cluded that fluoxetine, which theoretically raised serotonin levels,

was "an ideal drug for the treatment of depression." 26

This trail of reports in medical journals provided Eli Lilly with

the sound bites it needed to advertise its drug to doctors. The com¬

pany flooded medical journals with ads that featured good-looking

people who radiated happiness, the ads touting Prozac as equal in

efficacy to imipramine, and better tolerated. Science had proven

that psychiatry had a new and much improved pill for depression,

which appeared to correct a chemical imbalance in the brain.

The story told to the public

The story that had been told in psychiatric journals was certain to

resonate with the public. However, at this point, the market for

antidepressants was still moderate in size. When Prozac was ap¬

proved, Wall Street analysts predicted that it could generate $135 to

$400 million in annual sales for Eli Lilly. But the drug companies,

the APA, and the leaders of the NIMH were keen on expanding the

market for antidepressants, and the NIMH's DART "public aware¬

ness” campaign turned out to be the perfect vehicle for doing so.

290

ANATOMY OF AN EPIDEMIC

After the NIMH announced its plans for DART in 1986, it had

studied the public's beliefs about depression. A survey revealed that

only 12 percent of American adults would take a pill to treat it.

Seventy-eight percent said they "would live with it until it passed,”

confident they could handle it on their own. This was an attitude

consistent with what the NIMH had preached only fifteen years ear¬

lier, when Dean Schuyler, head of the depressive section, had told

the public that most depressive episodes "will run their course and

terminate with virtually complete recovery without specific inter¬

vention." There was epidemiological wisdom in the public's belief

that depression would pass, but the NIMH —once Shervert Frazier

and other biological psychiatrists took the helm —was intent on de¬

livering a different message.

The purpose of DART, the NIMH explained in 1988, was "to

change public attitudes so that there is greater acceptance of depres¬

sion as a disorder rather than a weakness." The public needed to

understand that it regularly went "underdiagnosed and under¬

treated," and that it could "be a fatal disease” if left untreated.

There were 31.4 million Americans who suffered from at least a

mild form of depression, the NIMH said, and it was important that

they get diagnosed. The public needed to be made aware that anti¬

depressants produced recovery rates of ”70% to 80% in compari¬

son with 20% to 40% for placebo.” The NIMH vowed to continue

DART indefinitely in order to "inform” the public of these

"facts.

The NIMH officially launched DART in May 1988, five months

after Prozac landed on pharmacy shelves. The NIMH enlisted

"labor, religious, educational groups" and businesses to help it

spread its message, and of course pharmaceutical companies and

NAMI had been on board from the start. The NIMH ran advertise¬

ments in the media, and Eli Lilly helped pay for the printing and dis¬

tribution of 8 million DART brochures titled "Depression: What

You Need to Know.” This pamphlet informed readers, among other

things, of the particular merits of "serotonergic" drugs for the dis¬

ease. "By making these materials on depressive illness available,

accessible in physicians' offices all over the country, important in¬

formation is effectively reaching the public in settings which

THE STORY THAT WAS

AND WASN’T TOLD

291

encourage questions, discussion, treatment, or referral," said NIMH

director Lewis Judd. 28

The remaking of the American mind was under way. This selling

of depression, which was being done under the guise of a "public

education” campaign, turned into one of the most effective market¬

ing efforts ever devised. Newspapers picked up on this story, sales

of Prozac began to soar, and then, on December 18, 1989, the

green-and-white pill officially gained celebrity status when New

York magazine put it on its cover, BYE, BYE BLUES, the headline

screamed, A NEW WONDER DRUG FOR DEPRESSION. In the article,

one "anonymous" user of Prozac said that on a scale of 1 to 100,

he now felt "over 100.” Thanks to this new miracle pill, the maga¬

zine concluded, psychiatrists felt that their "profession has been

buoyed." 29

Other such glowing stories quickly followed. On March 26,

1990, Newsweek's cover featured the green-and-white capsule

floating Nirvana-like over a beautiful landscape, PROZAC: A BREAK¬

THROUGH DRUG FOR DEPRESSION the magazine announced. Physi¬

cians were now writing 650,000 prescriptions for the pill each

month, and "nearly everyone has something nice to say about the

new treatment,” Newsweek said. Patients were loudly exclaiming,

"I never felt better!" 30 Three days later, Natalie Angier of the New

York Times, who arguably was the nation's most popular science

writer, explained that antidepressants "work by restoring the bal¬

ance of neurotransmitter activity in the brain, correcting an abnor¬

mal excess or inhibition of the electrochemical signals that control

mood, thoughts, appetite, pain and other sensations." This new

drug. Dr. Francis Mondimore told Angier, "is not like alcohol or

Valium. It's like antibiotics." 31 Television shows weighed in with a

similar message, and on 60 Minutes, Lesley Stahl told the inspiring

story of a woman, Maria Romero, who, after a decade of horrible

depression, had been reborn on Prozac. "Somebody, something left

my body and another person came in," Romero said. Stahl happily

explained the biological cure that was at work: "Most doctors

believe that chronic depression like Romero's is caused by a chemi¬

cal imbalance in the brain. To correct it, the doctor prescribed

Prozac." 32

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ANATOMY OF AN EPIDEMIC

Scientology to the Rescue

Fairly early on, there was a moment when this wonder-drug story

threatened to fall apart. The problem, of course, was that fluoxetine

did in fact stir suicidal and violent thoughts in some people, and

during the summer of 1990, the issue of Prozac's safety burst into

the news. And it was then, at that critical moment, that Scientology

proved so useful to Eli Lilly and the psychiatric establishment.

By 1990, so many people had suffered bad reactions to fluoxetine

that a national Prozac Survivors Support Group had formed. Many

harmed by the drug had taken their complaints to lawyers, and two

lawsuits in particular grabbed the public's attention. First, on July

18, newspapers reported that a Long Island woman, Rhoda Hala,

was suing Eli Lilly because, after going on Prozac, she had slashed

her wrists and "other parts of her body hundreds of times." 33 Two

weeks later, newspapers reported on a lawsuit related to a mass

murder committed by a crazed Kentucky man. Five weeks after

starting the drug, Joseph Wesbecker walked into a Louisville print¬

ing plant where he had worked and opened fire with an AK-47

assault rifle, killing eight and wounding twelve. The Citizens Com¬

mission on Human Rights quickly issued a press release urging

Congress to ban this "killer drug,” and that's when Eli Lilly

pounced. These lawsuits, Eli Lilly loudly announced, "are being

drummed up by the Scientology group, which has a history of criti¬

cizing the use of psychiatric drugs." 34

This was the start of Eli Lilly's campaign to save its blockbuster

drug. "Lilly can go down the tubes if we lose Prozac,” wrote chief

medical officer Leigh Thompson, in a harried 1990 memo. 35 The

company quickly honed a four-point message for the media: This

was an issue being raised by Scientologists; extensive clinical trials

had shown that Prozac was a safe drug; the suicidal and homicidal

events were "in the disease, not the drug"; and "people who could

be helped are being scared away from treatment, and that's the real

public menace." 36 The company ran media-training sessions for the

academic psychiatrists it hired as consultants, getting them to prac¬

tice their delivery of this message. "Frankly, I was unimpressed with

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293

the performance of our outside professionals," company vice-

president Mitch Daniels complained to Thompson after one such

practice session in April 1991. The company would "mandate” that

the academic psychiatrists perform better "in their future training

sessions," he said.”

An article that appeared in the Wall Street Journal on April 19,

1991, showed that Eli Lilly's training sessions had paid off. "Scien¬

tology," the paper informed its readers, was a "quasi-religious/

business/paramilitary organization" that was "waging war on psy¬

chiatry." The group had attacked Prozac's safety even though "doc¬

tors unaffiliated with Lilly” had found, during the clinical trials,

that there was "a lower tendency toward suicidal thinking with

Prozac than with other antidepressants, or with the starch capsules

given to a control group.” It was, Leigh Thompson said, a "demor¬

alizing revelation to watch twenty years of solid research by doctors

and scientists shouted down in twenty-second sound bites by Scien¬

tologists and lawyers." Indeed, the Wall Street Journal reported, Eli

Lilly, in response to concerns about Prozac's safety, had asked "sui¬

cide experts" to re-scrutinize the trial data, but they had "concluded

that nothing in the clinical trials linked suicidal thinking —common

in depression patients —to Prozac.” It was the disease, not the drug,

and that was the tragedy, explained Jerrold Rosenbaum, a Harvard

psychiatrist at Massachusetts General Hospital. "The public's fear

of Prozac as a result of this campaign has itself become a potentially

serious public-health problem as people stay away from treat¬

ment." 38

Rosenbaum, naturally, was one of Eli Lilly's "outside profession¬

als.” As the Boston Globe later reported, he "sat on a marketing ad¬

visory panel for Lilly before Prozac was launched," his relationship

to Eli Lilly a "cozy” one. 39 But the Wall Street Journal presented

him as an independent expert, one of the nation's top depression

doctors, and so readers could only draw one conclusion: This was

an issue conjured up by noxious Scientologists, rather than a legiti¬

mate concern. Other newspapers and magazines framed the issue in

that way, with Time, in May of that year, publishing a scathing

cover story on Scientology, calling it a "criminal organization" that

attracted "psychopaths." 40

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ANATOMY OF AN EPIDEMIC

On September 20, 1991, the FDA did convene a hearing on

whether Prozac elevated the risk of suicide, but the advisory panel,

which was dominated by physicians with ties to pharmaceutical

companies, showed little interest in seriously investigating this ques¬

tion. Although more than two dozen citizens testified on the harm

that the drug could cause, the panel made sure that the scientific

discussion was limited to presentations that supported Eli Lilly's po¬

sition that fluoxetine was perfectly safe. As the Wall Street Journal

reported, the scientific data presented at the hearing proved that

"fluoxetine doesn't lead to increased suicide or suicidal thinking,

and, in fact, show that the drug helps alleviate these conditions.”

The entire controversy, one Lilly supporter told the Journal, was a

"complete fiction" that had been "organized and funded by an anti¬

psychiatric group.” 41

At that moment, Eli Lilly and all of psychiatry had achieved a

public relations victory of lasting importance. The wonder-drug

aura around Prozac had been restored, and the public and the

media had been conditioned to associate criticism of psychiatric

drugs with Scientology. The debate over the merits of these drugs

now seemed to feature the nation's top scientists and doctors on one

side and religious kooks on the other, and if that were so, the public

could be certain where the truth lay. Other SSRIs came to market,

sales of Prozac hit the $1 billion mark in 1992, and then, in 1993,

Brown University psychiatrist Peter Kramer, in his book Listening

to Prozac, pushed the wonder-drug story up a notch. Prozac, he

wrote, was making some patients "better than well.” An era of

"cosmetic psychopharmacology" was dawning, Kramer suggested,

with psychiatry likely to have pills in the near future that could give

normal people whatever personality they wanted. His book spent

twenty-one weeks on the New York Times bestseller list, and soon

Newsweek was warning readers that it was time for society to start

grappling with the ethical questions raised by psychiatry's new

powers. "The same scientific insights into the brain that led to the

development of Prozac are raising the prospect of nothing less than

made-to-order, off-the-shelf personalities," Newsweek explained in

1994. Will those who refuse to "give their brain a makeover," the

magazine asked, be left behind?

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295

Gushed neuropsychiatrist Richard Restate: "For the first time in

human history, we will be in a position to design our own brains." 42

America Fooled

As the Prozac story unfolded in the media, surely the ghost of John

Brinkley was smiling somewhere. He had transfixed listeners to his

radio show with tales of the wonders of transplanted goat gonads,

and now here was a storytelling process that had transformed a

drug "totally unsuited” for treating depression into a miracle com¬

pound, with psychiatrists publicly wringing their hands over their

new godlike powers to shape the human mind. Should they worry

about making people "better than well"? Would our society lose

something precious if everybody were happy all the time? The wide¬

spread medicating of the American mind was now under way,

and—as a very quick review will reveal —it was this same story¬

telling process that supported the launch of Xanax as a drug for

panic disorder and the atypical antipsychotics for schizophrenia.

Once those "second-generation" drugs became blockbusters, the

drug companies and academic psychiatrists began touting psychi¬

atric drugs of all kinds for use in children, this storytelling sweeping

millions of American youth into the "mental illness" bin.

Xanax

Xanax (alprazolam) was approved by the FDA as an anti-anxiety

agent in 1981, and then Upjohn set out to get it approved for panic

disorder, which had been newly identified as a discrete condition for

the first time in DSM-III (1980). As a first step, it hired former

NIMH director Gerald Klerman to co-chair its "steering commit¬

tee” for the testing process, and it paid Daniel Freedman, editor of

the Archives of General Psychiatry, to be an assistant to its "divi¬

sion of medical affairs." 43 This was just part of the company's

efforts to co-opt academic psychiatry: "The most senior psychia¬

trists in the world were flooded with offers of consultancies" from

ANATOMY OF AN EPIDEMIC

296 •

Upjohn, said Isaac Marks, an expert in anxiety disorders at the

Institute of Psychiatry in London.* 4

Klerman and Upjohn designed Upjohn's Cross National Collabo¬

rative Panic Study in a manner that could be expected to produce a

poor placebo response. Patients who had been on benzodiazepines

were allowed into the study, which meant that many in the placebo

group would in fact be going through the horrors of benzodiazepine

withdrawal, and thus could be expected to be extremely anxious

during the first weeks of the trial. Nearly one-fourth of the placebo

patients had traces of benzodiazepines in their blood when the

treatment period began. 45

Benzodiazepines are known to work quickly, and that proved

true in this study. At the end of four weeks, 82 percent of the alpra¬

zolam patients were "moderately improved” or "better," versus 43

percent of the placebo group. However, during the next four weeks,

the placebo patients continued to improve, while the alprazolam

patients did not, and by the end of the eighth week, there "was no

significant difference between the groups" on most of the rating

scales, at least among the patients who remained in the study. The

alprazolam group also experienced a variety of troubling side effects:

sedation, fatigue, slurred speech, amnesia, and poor coordination.

One of every twenty-six alprazolam patients suffered a "serious" re¬

action to the drug, such as mania or aggressive behavior. 46

At the end of eight weeks, the patients were tapered from their

medication for four weeks and then followed while medication-free

for another two weeks. The results were predictable. Thirty-nine

percent of those withdrawn from alprazolam "deteriorated signifi¬

cantly," their panic and anxiety skyrocketing to such an extent they

had to start taking the medication again. Thirty-five percent of the

alprazolam patients suffered "rebound” panic and anxiety symp¬

toms more severe than when the study began, and an equal per¬

centage suffered a host of debilitating new symptoms, including

confusion, heightened sensory perceptions, depression, a feeling that

insects were crawling over them, muscle cramps, blurred vision, di¬

arrhea, decreased appetite, and weight loss. 47

In sum, at the end of fourteen weeks, the drug-exposed patients

were worse off than the placebo group: They were more phobic,

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297

The Xanax Study

9 -

8 -

7 -

Placebo

Active treatment

Drug taper

Off drug

Baseline Week

Week Week Week Week

4 8 9 12

Week Week

13 14

In Upjohn's study of Xanax, patients were treated with the drug or placebo for eight weeks. Then

this treatment was slowly withdrawn (weeks 9 through 12), and during the last two weeks

patients didn't receive any treatment. The Xanax patients fared better during the first four weeks,

which is the result that the Upjohn investigators focused on in their journal articles. However,

once the Xanax patients began withdrawing from the the drug, they suffered many more panic

attacks than the placebo patients, and atthe end ofthe study were much more symptomatic.

Source: Ballenger, C. "Alprazolam in panic disorder and agoraphobia ."Archives of General Psych-

iatry 45 (1988): 41 3-22. Pecknold, C. "Alprazolam in panic disorder and agoraphobia." Archives of

General Psychiatry 45 (1 988): 429-36.

more anxious, more panic stricken, and doing worse on a "global

scale” that assessed overall well-being. Forty-four percent had been

unable to get off the drug, on their way to a lifetime of addiction. In

every way, the results painted a powerful portrait of the benzo trap:

This was a drug that worked for a short time, then its efficacy over

a placebo petered out, and yet when patients tried to go off the

drug, they became quite sick and many couldn't kick the habit. The

first few weeks of relief came at a very high long-term cost, with

those stuck on the drug —as previous benzodiazepine studies had

shown —likely to end up physically, emotionally, and cognitively

impaired.

The Upjohn investigators published three articles in the Archives

of General Psychiatry in May 1988, and anyone who carefully re¬

viewed the data could see the harm caused by alprazolam. But in

order for Xanax to be successfully marketed, Upjohn needed its in¬

vestigators to draw a different sort of conclusion, and so they did,

ANATOMY OF AN EPIDEMIC

298

particularly in the abstracts of the three articles. First, they focused

their attention on the four-week results (rather than the eight-week

outcomes at the end of the treatment period), announcing that "al¬

prazolam was found to be effective and well-tolerated.” 48 Next,

they noted that 84 percent of the alprazolam patients had finished

the eight-week study, which was evidence that "patient acceptance

of alprazolam was high." Although their alprazolam patients regu¬

larly exhibited such problems as "slurred speech, amnesia” and

other signs of "impaired mentation," they still concluded that the

drug had "few side effects and is well tolerated." 49 Finally, while

they acknowledged that some alprazolam patients fared poorly

when the drug was withdrawn, they reasoned that it had been used

for too short a period and the withdrawal done too abruptly. "We

recommend that patients with panic disorder be treated for a longer

period, at least six months," they said. 50

In London, Isaac Marks and several of his colleagues at the Insti¬

tute of Psychiatry subsequently pointed out how transparently

ridiculous this all was. In a letter to the Archives of General Psychi¬

atry, they observed that since the alprazolam patients "were in a

worse state than patients receiving placebo" at the end of the study,

the finding by the Upjohn investigators that the drug was effective

and well tolerated could only be seen as "biased and arguable." 51

The entire affair, Marks subsequently wrote, "is a classic demon¬

stration of the hazards of research funded by industry." 52

Yet the fact that the alprazolam patients came to such a bad end,

with many on a path to a lifelong addiction, did not deter Upjohn,

Klerman, the APA, and the NIMH from touting Xanax's benefits to

the American public. The same marketing machinery that had made

Prozac a bestseller was rolled out again. Upjohn sponsored a sym¬

posium at the APA's 1988 meeting where the "expert panel” high¬

lighted the four-week results. Robert Pasnau, who had been head of

the APA in 1987, sent a glossy booklet on the Consequences of

Anxiety to APA members, an "educational" effort paid for by Up¬

john. Both Shervert Frazier and Gerald Klerman penned a "Dear

Doctor" letter that Upjohn included in the promotional literature it

sent to doctors about Xanax as a treatment for panic disorder. Up¬

john also gave $1.5 million to the APA so that it could mount a

THE STORY THAT WAS

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299

DART-like campaign to "educate” psychiatrists, health-care workers,

and the public about panic disorder, which was said to be "under¬

recognized and undertreated." 53 Finally, the NIMH chipped in too,

identifying panic disorder as a priority concern and sponsoring a

conference in 1991 on it, with its panel of experts designating "high

potency benzodiazepines"— this would be Xanax —as one of the

two "treatments of choice." 54

The FDA approved Xanax as a treatment for panic disorder in

November 1990, and many newspapers and magazines ran the

usual features, IN A PANIC? HELP IS ON THE WAY, a St. Louis Post-

Dispatch headline announced. Treatment, the paper said, helped 70

to 90 percent of those with the debilitating condition, which af¬

flicted "4 million adults in this country." 55 The Associated Press ex¬

plained that "a biochemical malfunctioning in the brain is believed

to be one of the causes of panic attacks. Xanax can block the at¬

tacks by interacting with several different systems in the brain." 56 In

the Chicago Sun-Times, Dr. John Zajecka at Rush Medical College

in Chicago announced that "Xanax is the fastest acting and least

toxic” of medications for the disorder. 57 Once again, a very effec¬

tive, safe drug had arrived on the market, and in 1992, Xanax be¬

came the fifth most frequently prescribed medication in the United

States. 55

Not so atypical

Even as Xanax was on the way to market as a treatment for panic

disorder, Janssen was conducting tests of risperidone, a new drug

for schizophrenia. By this time, the methods that pharmaceutical

firms were employing to create new "blockbuster" psychotropics

were becoming quite well practiced, with nearly everyone employ¬

ing the Prozac model of drug development, and so Janssen, like Eli

Lilly and Upjohn, designed trials that were biased in favor of its

drug. In particular, Janssen compared multiple doses of risperidone

to a high dose of haloperidol (Haldol), as it could then be relatively

certain that one of the risperidone doses would have a good safety

profile in comparison to the old "standard” neuroleptic. As FDA

reviewers noted, these studies were "incapable” of providing any

300

ANATOMY OF AN EPIDEMIC

meaningful comparison of the two drugs. 59 In the FDA's letter of ap¬

proval to Janssen, Robert Temple, director of the Office of Drug

Evaluation, made this clear:

We would consider any advertisement or promotion labeling

for RISPERDAL false, misleading, or lacking fair balance

under section 502 (a) and 502 (n) of the ACT if there is pres¬

entation of data that conveys the impression that risperidone

is superior to haloperidol or any other marketed antipsy¬

chotic drug product with regard to safety or effectiveness. 60

However, while the FDA could prohibit Janssen from placing

advertisements touting its drug as superior to haloperidol, it did not

have authority over what the academic psychiatrists hired by

Janssen could say. This was the commercial beauty of the "partner¬

ship” that had emerged between psychiatry and the pharmaceutical

industry during the 1980s —the academic doctors could make

claims, both in their medical journals and to the public, that the

FDA considered false in kind. In this case, they published more than

twenty articles in psychiatric journals touting risperidone as equal

or superior to haloperidol in reducing positive symptoms of schizo¬

phrenia (psychosis) and superior to haloperidol in improving nega¬

tive symptoms (lack of emotion). The academic doctors reported

that risperidone reduced hospital stays, improved the patient's abil¬

ity to function socially, and reduced hostility. "Risperidone has im¬

portant advantages compared with haloperidol," they wrote in the

journal of Clinical Psychiatry. "When administered in an effective

dose range, risperidone produced greater improvements on all five

dimensions of schizophrenia." 61

Once again, this was a scientific story of a new and improved

treatment, and in their interviews with the media, Janssen's investi¬

gators told of a wonder drug. This new agent, the Washington Post

reported, "represents a glimmer of hope for a disease that until re¬

cently had been considered hopeless.” Risperidone, it explained, did

not "cause sedation, blurred vision, impaired memory or muscle

stiffness, side effects commonly associated with an earlier genera¬

tion of antipsychotic drugs." 62 The New York Times, quoting

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301

Richard Meibach, Janssen's clinical research director, reported that

"no major side effects" had appeared in the two-thousand-plus pa¬

tients treated with risperidone in the clinical trials.* The drug was

thought to "relieve schizophrenia symptoms by blocking excessive

flows of serotonin or dopamine, or both," the paper said.* 3

The atypical revolution was on. Risperdal apparently restored

sanity by balancing multiple neurotransmitters in the brain, and it

seemed to cause no side effects of any note. In 1996, Eli Lilly

brought Zyprexa (olanzapine) to market, and the public story of the

wonders of atypicals got ramped up another notch.

As had become customary, Eli Lilly employed trials that were

"biased by design" against haloperidol, the FDA concluded. As a

result, its large phase III trial, which wasn't placebo controlled, pro¬

vided "little useful efficacy data." As for olanzapine's safety profile,

twenty patients treated with the drug during the trials died, 22

percent suffered a "serious" adverse event (higher than in the

haloperidol patients), and two-thirds failed to complete the studies.

Olanzapine, the data suggested, made patients sleepy and fat, and

caused such problems as Parkinsonian symptoms, akathisia, dysto¬

nia, hypotension, constipation, tachycardia, diabetes, seizures, leak¬

ing breasts, impotence, liver abnormalities, and white blood cell

disorders. Furthermore, warned the FDA's Paul Leber, since olanza¬

pine blocked receptors for many types of neurotransmitters, "no

one should be surprised if, upon marketing, events of all kinds and

severity not previously identified are reported in association with

olanzapine's use." 64

That was the story told by the trial data. The story that Eli Lilly

wanted to appear in the medical journals and newspapers was that

Zyprexa was better than Janssen's Risperdal, and so that's the story

that its hired guns told. Psychiatrists from academic medical schools

announced that olanzapine worked in a more "comprehensive” man¬

ner than either risperidone or haloperidol. It was a well-tolerated

* In fact, eighty-four patients treated with risperidone had suffered a "serious

adverse event," which the FDA defined as a life-threatening event or one that

required hospitalization.

302

ANATOMY OF AN EPIDEMIC

agent that led to global improvement—it reduced positive symp¬

toms, caused fewer motor side effects than other antipsychotics,

and improved negative symptoms and cognitive function. 65 This

second atypical was better than the first, and the Wall Street Journal

ran with that angle. Zyprexa, it announced, "has substantial advan¬

tages” over other current therapies. "The real world,” explained

John Zajecka, from Rush Medical College, "is finding that Zyprexa

has fewer extrapyramidal side effects than Risperdal." 66 Zyprexa is

"a potential breakthrough of tremendous magnitude," Stanford

University psychiatrist Alan Schatzberg told the New York Times. 67

The only question now seemed to be whether Zyprexa was truly

better than Risperdal, and after AstraZeneca brought a third atypi¬

cal to market, Seroquel, the media settled on the notion that collec¬

tively the new atypicals were a dramatic improvement over the older

drugs. They were, Parade told its readers, "far safer and more effec¬

tive in treating negative symptoms, such as difficulty in reasoning

and speaking in an organized way." 66 The newer drugs, the Chicago

Tribune announced, "are safer and more effective than older ones.

They help people go to work." 69 Wrote the Los Angeles Times, "It

used to be that schizophrenics were given no hope of improving. But

now, thanks to new drugs and commitment, they're moving back

into society like never before.” 70 NAMI chimed in, too, publishing

a book titled Breakthroughs in Antipsychotic Medications, which

helpfully explained that these new drugs "do a better job of balanc¬

ing all of the brain chemicals, including dopamine and serotonin.” 71

On and on it went, and finally NAMI's executive director, Laurie

Flynn, told the press that the promised land had at last been reached:

"These new drugs truly are a breakthrough. They mean we should

finally be able to keep people out of the hospital, and it means that

the long-term disability of schizophrenia can come to an end." 72

Lancet Asks a Question

That was the sequence of storytelling that led to the explosive rise in

the use of psychiatric drugs in the United States. First, American

THE STORY THAT WAS

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303

psychiatrists touted Prozac as a wonder drug, next they hailed

Xanax as a safe and effective therapy for panic disorder, and finally

they informed the public that atypical antipsychotics were "break¬

through” medications for schizophrenia. In this way, they rejuve¬

nated the market for psychiatric medications, even though the

clinical studies of the new drugs had not told of any therapeutic

advance.

At least in scientific circles, the "wonder drug” glow around the

second-generation psychotropics has long since disappeared. As we

learned earlier, the SSRIs were reported in 2008 to provide a mean¬

ingful clinical benefit only to severely depressed patients. Xanax is

now understood to be much more addictive than Valium, with vari¬

ous investigators determining that two-thirds of people who take it

for any length of time have trouble getting off it.” As for the top¬

selling atypicals, the hyping of these drugs is now viewed as one of

the more embarrassing episodes in psychiatry's history, as one

government-funded study after another failed to find that they were

any better than the first-generation antipsychotics. In 2005, the

NIMH's "CATIE Trial" determined that there were "no significant

differences” between the atypicals and their predecessors, and even

more troubling, in this study neither the new drugs nor the old ones

could really be said to work. Seventy-four percent of the 1,432 pa¬

tients were unable to stay on the medications, mostly because of

their "inefficacy or intolerable side effects." 74 A study by the U.S.

Department of Veterans Affairs came to a similar conclusion about

the relative merits of atypicals and the older drugs, and then, in

2007, British psychiatrists reported that schizophrenia patients, if

anything, had a better "quality of life” on the old drugs than on the

new ones. 75 All of this led two prominent psychiatrists to write in

the Lancet that the story of the atypicals as breakthrough medica¬

tions could now be "regarded as invention only,” a tale concocted

"by the drug industry for marketing purposes and only now being

exposed.” Yet, they wondered, "how is it that for nearly two

decades we have, as some have put it, 'been beguiled' into thinking

they were superior?" 76

History, as readers of this book can attest, reveals the answer to

that question. The seed for the atypicals story was planted in the

304

ANATOMY OF AN EPIDEMIC

early 1980s, when the APA embraced "biological psychiatry" as a

story that could be successfully marketed to the public. This was

also a story that the field, as a whole, desperately wanted to believe

in, and soon Nancy Andreasen and others were telling of a revolu¬

tion that was under way, with mental illnesses finally giving up their

biological secrets, even though nobody could precisely explain what

those secrets were. That story gained steam, prepping the public to

believe that therapeutic advances were on the way, and as pharma¬

ceutical companies brought new medications to market, they hired

the top psychiatrists in the country to tell of how these new won¬

drous drugs "balanced” brain chemistry. And it was that co-opting

of academic medicine that gave the story its credibility. This was a

story told by Harvard Medical School psychiatrist Jerrold Rosen¬

baum, by former NIMH director Gerald Klerman, and by Stanford

University psychiatrist Alan Schatzberg.

Of course we, as a society, believed it.

Silencing Dissent

As we have seen, American psychiatry has told the public a false story

over the past thirty years. The field promoted the idea that its drugs

fix chemical imbalances in the brain when they do no such thing,

and it grossly exaggerated the merits of the second-generation

psychotropics. In order to keep that tale of scientific progress afloat

(and to protect its own belief in that tale), it has needed to squelch

talk about the harm that the drugs can cause.

Psychiatry's policing of its own ranks began in earnest in the late

1970s, when Loren Mosher was ousted from the NIMH for having

run his Soteria experiment. The next prominent psychiatrist to end

up on psychiatry's hit list was Peter Breggin. Although he is known

today for his "antipsychiatry” writings, he, too, had once been on

the fast track at the NIMH. After finishing his residency at a Har¬

vard Medical School hospital, Breggin went to the NIMH in 1966

to work on developing community mental health centers. "I was

still the young hotshot guy," he recalled, in an interview. "I thought

THE STORY THAT WAS

AND WASN’T TOLD

305

I would be the youngest professor of psychiatry in the history of

Harvard Medical School. That was the trajectory I was on."” How¬

ever, he saw that the future belonged to biological psychiatry, as op¬

posed to the social psychiatry that interested him, and he left the

NIMH to go into private practice. Soon he began writing about the

hazards of electroshock and psychiatric drugs, which, he argued,

"worked” by disabling the brain. After a number of heated battles

with the APA's leaders, Breggin appeared in 1987 on Oprah Win¬

frey's television show, where he spoke about tardive dyskinesia and

how that dysfunction was evidence that neuroleptics damaged the

brain. His comments so infuriated the APA that it sent a transcript

of the show to NAMI, which in turn filed a complaint with the

Maryland State Commission on Medical Discipline, asking that it

take away Breggin's medical license on the grounds that his state¬

ments had caused schizophrenia patients to stop taking their medi¬

cations (and thus caused harm). Although the commission decided

not to take any action, it did conduct an inquiry (rather than sum¬

marily dismissing NAMI's complaint), and the message to everyone

in the field was, once again, quite clear.

"I think the interesting thing is that Loren [Mosher] and I took

on scientifically the two sides of the issue,” Breggin said. "Loren

took on the issue that there is a better treatment than drugs for

schizophrenia. I took on the treatments —the drugs, electroshock,

and psychosurgery. And what this showed is that it didn't matter

which end you wanted to take, they were willing to destroy your

career. That is the lesson."

The career setback that Irish psychiatrist David Healy experi¬

enced was, in some ways, reminiscent of Mosher's fall from grace.

During the 1990s, he earned a reputation as one of the field's lead¬

ing historians, his writings focusing on the psychopharmacology

era. He had served as secretary of the British Association for Psy¬

chopharmacology, and in early 2000, he accepted an offer from the

University of Toronto's Centre for Addiction and Mental Health to

head up its mood and anxiety program. Up until that moment, he

was very much part of the psychiatric establishment, just as Mosher

had been. However, for several years he had been interested in the

question of whether SSRIs could stir suicide, and he had recently

306

ANATOMY OF AN EPIDEMIC

completed a "healthy volunteers" study. Two of the twenty volun¬

teers had become suicidal after they were exposed to an SSRI, which

clearly showed that the drug could cause such thoughts. Not long

after he accepted the Toronto job, he presented his results at a meet¬

ing of the British Association for Psychopharmacology. There, one

of the most prominent figures in American psychiatry warned him

to knock it off. "He told me that my career would be destroyed if I

kept on showing results like the ones I'd just shown, that I had no

right to bring out hazards of the pills like these," Healy said.™

In November of 2000, only a few months before he was sched¬

uled to start his new job at the University of Toronto, Healy gave a

talk on the history of psychopharmacology at a colloquium orga¬

nized by the school. In his presentation, Healy spoke about prob¬

lems that had arisen with neuroleptics since their introduction in the

1950s, briefly reviewed the data showing that Prozac and other

SSRIs elevated the risk of suicide, and then observed in passing that

outcomes for affective disorders are worse today than they were a

century ago. This, he observed, shouldn't be happening if "our

drugs really worked." 79

Although the audience subsequently rated his talk as the collo¬

quium's best for content, by the time Healy arrived back in Wales,

the University of Toronto had rescinded the job offer. "While you

are held in high regard as a scholar of the history of modern psychi¬

atry, we do not feel your approach is compatible with the goals for

development of the academic and clinical resources that we have,"

wrote the Centre's head psychiatrist, David Goldbloom, in an

e-mail. 80 Once more, others in the field could draw only one lesson.

"The message is that it is a bad idea to speak out, and that the idea

that treatments might not work or might not be best managed by

being entrusted to doctors is beyond the pale,” Healy said in an in¬

terview. 81

Numerous others can attest to the fact that it is a "bad idea" to

speak out. Nadine Lambert, a psychologist at the University of Cal¬

ifornia at Berkeley, conducted a long-term study of children treated

with Ritalin and found that, as young adults, they had elevated

rates of cocaine abuse and cigarette smoking. After she reported her

results at a 1998 NIH conference, the National Institute on Drug

THE STORY THAT WAS

AND WASN'T TOLD

307

Abuse stopped funding her work. In 2000, when Joseph Glen-

mullen, a clinical instructor in psychiatry at Harvard Medical

School, authored Prozac Backlash, which detailed the many prob¬

lems associated with the use of SSRIs, Eli Lilly mounted a campaign

to discredit him. A public-relations firm gathered critical comments

from several prominent psychiatrists, who derided Glenmullen as a

"nobody" in the field, and then it mailed these "reviews" to various

newspapers. "It's a dishonest book, it's manipulative, it's mischie¬

vous," said Harvard Medical School psychiatrist Jerrold Rosen¬

baum, even though he was a colleague of Glenmullen's. The press

release naturally did not mention that Rosenbaum was an Eli Lilly

consultant. 82 Next up on the chopping block: Gretchen LeFever, a

psychologist at East Virginia Medical School. After she published

research showing that an overly high number of children in Virginia

schools were being diagnosed with ADHD, an anonymous "whistle¬

blower" charged her with scientific misconduct. Her federal research

funds were cut off and her computers were seized, and while she

was subsequently cleared of any misconduct, her career had still

been derailed.

Said Healy: "The thought-control aspect of things in psychiatry

today is like old-style Eastern European social control."

Hiding the Evidence

The third aspect to the storytelling process that has led to our socie¬

tal delusion about the merits of psychiatric drugs is easy to docu¬

ment. Imagine what our beliefs would be today if, over the past

twenty years, we had opened our newspapers and read about the

following findings, which represent but a sampling of the outcome

studies we reviewed earlier in the book:

1990: In a large, national depression study, the eighteen-

month stay-well rate was highest for those treated with

psychotherapy (30 percent) and lowest for those treated

with an antidepressant (19 percent). (NIMH)

308

ANATOMY OF AN EPIDEMIC

1992: Schizophrenia outcomes are much better in poor

countries like India and Nigeria, where only 16 percent of

patients are regularly maintained on antipsychotics, than

in the United States and other rich countries, where contin¬

ual drug usage is the standard of care. (World Health

Organization)

1995: In a six-year study of 547 depressed patients,

those who were treated for the disorder were nearly seven

times more likely to become incapacitated than those who

weren't, and three times more likely to suffer a "cessation"

of their "principal social role.” (NIMH)

1998: Antipsychotic drugs cause morphological changes

in the brain that are associated with a worsening of schizo¬

phrenia symptoms. (University of Pennsylvania)

1998: In a World Health Organization study of the mer¬

its of screening for depression, those diagnosed and treated

with psychiatric medications fared worse —in terms of

their depressive symptoms and their general health —over

a one-year period than those who weren't exposed to the

drugs. (WHO)

1999: When long-term benzodiazepine users withdraw

from the drugs, they become "more alert, more relaxed,

and less anxious." (University of Pennsylvania)

2000: Epidemiological studies show that long-term out¬

comes for bipolar patients today are dramatically worse

than they were in the pre-drug era, with this deterioration

in modern outcomes likely due to the harmful effects of

antidepressants and antipsychotics. (Eli Lilly; Harvard

Medical School)

2001: In a study of 1,281 Canadians who went on

short-term disability for depression, 19 percent of those

who took an antidepressant ended up on long-term dis¬

ability, versus 9 percent of those who didn't take the med¬

ication. (Canadian investigators)

2001: In the pre-drug era, bipolar patients did not suffer

cognitive decline over the long term, but today they end up

THE STORY THAT WAS

AND WASN’T TOLD

309

almost as cognitively impaired as schizophrenia patients.

(Sheppard Pratt Health System in Baltimore)

2004: Long-term benzodiazepine users suffer cognitive

deficits "moderate to large” in magnitude. (Australian sci¬

entists)

2005: Angel dust, amphetamines, and other drugs that

induce psychosis all increase D 2 HIGH receptors in the

brain; antipsychotics cause this same change in the brain.

(University of Toronto)

2005: In a five-year study of 9,508 depressed patients,

those who took an antidepressant were, on average, symp¬

tomatic nineteen weeks a year, versus eleven weeks for

those who didn't take any medication. (University of Cal¬

gary)

2007: In a fifteen-year study, 40 percent of schizophre¬

nia patients off antipsychotics recovered, versus 5 percent

of the medicated patients. (University of Illinois)

2007: Long-term users of benzodiazepines end up

"markedly ill to extremely ill" and regularly suffer from

symptoms of depression and anxiety. (French scientists)

2007: In a large study of children diagnosed with ADHD,

by the end of the third year "medication use was a signifi¬

cant marker not of beneficial outcome, but of deteriora¬

tion.” The medicated children were also more likely to

engage in delinquent behavior; they ended up slightly

shorter, too. (NIMH)

2008: In a national study of bipolar patients, the major

predictor of a poor outcome was exposure to an anti¬

depressant. Those who took an antidepressant were nearly

four times as likely to become rapid cyclers, which is asso¬

ciated with poor long-term outcome. (NIMH)

A check of newspaper archives reveals that the psychiatric estab¬

lishment has thoroughly succeeded in keeping this information from

the public. I searched for accounts of these studies in the New York

Times archives and in the LexisNexis database, which covers most

ANATOMY OF AN EPIDEMIC

310

U.S. newspapers, and I couldn't find a single instance where the

results were accurately reported.*

Newspapers, of course, would have been happy to publish these

study results. However, medical news is typically generated in this

way: The scientific journals, the NIH, medical schools, and pharma¬

ceutical companies issue press releases touting certain findings as

important, and reporters then sift through the releases to identify

the ones they deem worthy of writing about. If no press releases are

issued, or there is no other effort by the medical community to pub¬

licize the findings, then no stories appear. We can even document

this blackout process at work in the NIMH's handling of Martin

Harrow's outcomes study. In 2007, the year he published his results

in the Journal of Nervous and Mental Disease, the NIMH issued

eighty-nine press releases, many on inconsequential matters. But it

did not issue one on Harrow's findings, even though his was ar¬

guably the best study of the long-term outcomes of schizophrenia

patients that had ever been done in the United States. 83 It's fair to

say that if the results had been the reverse, the NIMH would have

sounded the press-release gong and newspapers across the country

would have touted the findings.

Although reports about most of the studies listed above simply

never appeared in newspapers, there were a couple of instances

when psychiatrists were forced to say something to reporters about

one of the studies, and each time they spun the results. For example,

when the NIMH announced the three-year results from its MTA

study of ADHD treatments, it did not inform the public that stimu¬

lant usage during the third year was a "marker of deterioration."

Instead, it put out a press release with this headline: IMPROVEMENT

* There were newspaper reviews of my book Mad in America that mentioned

the WHO study of better schizophrenia outcomes in poor countries where pa¬

tients were not regularly maintained on the drugs, and since then, this informa¬

tion has become somewhat known. In addition, I mentioned Martin Harrow's

fifteen-year schizophrenia study in a talk I gave at Holy Cross College in Feb¬

ruary 2009, and that led to a February 8, 2009, article in the Worcester

Telegram and Gazette (Mass.) that discussed Harrow's work. That was the

first time that news of his study had appeared in any American newspaper.

THE STORY THAT WAS

AND WASN'T TOLD

• 311

FOLLOWING ADHD TREATMENT SUSTAINED FOR MOST CHILDREN.

That headline told of drugs that had been beneficial, and while the

text of the release did state that "continuing medication was no

longer associated with better outcomes by the third year," it also in¬

cluded a canned quote from lead author Peter Jensen stating that

there was still plenty of reason to keep children on Ritalin. "Our re¬

sults suggest that medication can make a long-term difference for

some children if it's continued with optimal intensity, and not

started or added too late in a child's clinical course." 84

If we want to get another look at this spinning process, we can

turn to a 1998 New York Times article that briefly told of the WHO

study on schizophrenia outcomes in rich and poor countries. After

interviewing psychiatrists about the study, the Times reporter wrote

that "schizophrenics generally responded better to treatment in less

developed countries than in more technologically developed coun¬

tries." 88 Responded better to treatment— readers could only assume

that schizophrenia patients in India and Nigeria responded better to

antipsychotics than patients in the United States and other rich

countries did. They had no way to know that "treatment" for 84

percent of the schizophrenia patients in the poor countries consisted

of being off the drugs.

In July 2009,1 also searched the NIMH and NAMI websites for

some mention of the studies listed above, and I found zilch. For in¬

stance, the NIMH website did not discuss the remarkable decline in

bipolar outcomes in modern times, even though Carlos Zarate, who

coauthored the 2000 article that documented this decline, was head

of the NIMH's mood and anxiety disorders research unit in 2009.

Similarly, NAMI's website didn't provide any information about

Harrow's study, even though it provides reason for parents of schiz¬

ophrenic children to be optimistic. Forty percent of those off med¬

ications recovered over the long term! But that finding directly

contradicted the message that NAMI has promoted to the public for

decades, and NAMI's website is sticking to that message. Antipsy¬

chotics, it informs the public, "correct an imbalance in the chemi¬

cals that enable brain cells to communicate with each other." 86

Finally, the entire outcomes history documented in this book is

missing from the 2008 edition of the APA's Textbook of Psychiatry,

312 • ANATOMY OF AN EPIDEMIC

which means that medical students training to be psychiatrists are

kept in the dark about this history." The book does not discuss "su¬

persensitivity psychosis.” It does not mention that antidepressants

may be depressogenic agents over the long term. It does not report

that bipolar outcomes are much worse today than they were forty

years ago. There is no discussion of rising disability rates. There is

no talk about the cognitive impairment that is seen in longtime

users of psychotropic drugs. The textbook authors are clearly famil¬

iar with many of the sixteen studies listed above, but, if they do

mention them, they don't discuss the relevant facts about medica¬

tion usage. The long-running study by Harrow, the textbook states,

reveals that there are some schizophrenia patients who "are able to

function without the benefit of continuous antipsychotic treat¬

ment.” The authors of that sentence didn't mention the stunning

difference in recovery rates for the unmedicated and medicated

groups; instead they crafted a sentence that told of the benefit of

continuous antipsychotic treatment. In a similar vein, while the

textbook briefly discusses the WHO study on the better outcomes

of schizophrenia patients in poor countries like India and Nigeria, it

does not mention that patients in those countries weren't regularly

maintained on antipsychotics. In a section on benzodiazepines, the

authors acknowledge that there are concerns about their addictive

properties, but then state that long-term outcomes for those who

stay on benzodiazepines are generally good, as most patients

"maintain their therapeutic gains."

There is a story that psychiatry doesn't dare tell, which shows

that our societal delusion about the benefits of psychiatric drugs

isn't entirely an innocent one. In order to sell our society on the

soundness of this form of care, psychiatry has had to grossly exag¬

gerate the value of its new drugs, silence critics, and keep the story

of poor long-term outcomes hidden. That is a willful, conscious

process, and the very fact that psychiatry has had to employ such

storytelling methods reveals a great deal about the merits of this

paradigm of care, much more than a single study ever could.

Tallying Up the Profits

"Receiving $750 checks for chatting with some

doctors during a lunch break was such easy money

that it left me giddy."

- PSYCHIATRIST DANIEL CARLAT (2007)'

The walk from Jenna's group home in Montpelier, Vermont, to the

town's Main Street is only two blocks long, and yet, on the late

spring morning I visited, it took us twenty minutes to travel that dis¬

tance, for Jenna had to stop every few steps and catch her balance,

with her aide, Chris, constantly putting his hand up behind her in

case she fell.* Jenna had first taken an antidepressant twelve years

earlier, when she was fifteen years old, and now she was on a daily

cocktail of eight drugs, including one for drug-induced Parkinson¬

ian symptoms. As we sat outside a cafe, Jenna told me her story, al¬

though at times —because of her problems with motor control —it

was difficult to understand her. Her tremors are so severe that when

she dunked her pastry, the coffee spilled and she had trouble bring¬

ing the pastry to her lips.

"I'm sooooooo messed up,” she says.

I had gone to the interview thinking that Jenna had been diag¬

nosed with tardive dyskinesia, an antipsychotic side effect that can

disable people. But it wasn't clear whether her motor impairments

* Although Jenna said that I could use her last name, her mother and

stepfather, who have legal guardianship, requested that I use her first name

only.

314

ANATOMY OF AN EPIDEMIC

were due to that particular type of drug-induced dysfunction or to a

more idiosyncratic drug-related process, and by the time the inter¬

view was over, Jenna had raised a new issue for me to think about.

She told of how psychiatrists and other mental health workers had

always resisted seeing any of her physical or emotional difficulties

as drug-caused, but instead had regularly blamed everything on her

illness, and, from her point of view, that was a thinking process dic¬

tated by monetary interests. If you wanted to understand the care

she'd received, you had to understand that she was valuable to the

pharmaceutical companies as a "consumer" of their medications.

"Nobody," Chris explains, "has addressed the fact that the drugs

may be causing her problems."

The first time that Jenna had been exposed to a psychiatric drug

was when she was in the second grade, and that episode suggested

that she would not be a good responder to psychotropics. Up until

that time Jenna had been a healthy child, a star on a local swim

team; only then she developed seizures, and when she was put on an

anticonvulsive agent, she developed severe motor problems, her

mother said, in a phone interview. But eventually the seizures went

away and once Jenna stopped taking the anticonvulsant, her motor

problems disappeared. Jenna took up horseback riding, excelling in

"show-jumping competition. "She was back to being totally nor¬

mal," her mother recalled.

When Jenna entered ninth grade, her mother and stepfather de¬

cided to send her to an elite boarding school in Massachusetts, as

they didn't trust the public schools in Tennessee, and it was then

that her behavioral and emotional problems began. She was kicked

out of that first school and sent to a second one for troubled teens,

where she "got into all that Gothic stuff" and began "acting out"

sexually, her mother said. Then, on a dare one night, Jenna stole a

package of condoms from a drugstore and "freaked out" when she

was arrested. Now she was sent to a third boarding school and

prescribed Paxil.

"The minute she takes that drug, she starts shaking,” her mother

said. "I tell the doctor, 'Oh my gosh, it is from the medicine.' The

doctor says, 'Oh no, it's not the medicine.' I said, 'Yes it is.' We went

TALLYING UP THE PROFITS

315

from one doctor to another, doing test after test, but they couldn't

find anything and so they kept her on the medications, which made

everything worse. They just wouldn't listen to me.”

In addition to the tremors, Jenna became suicidal while taking

Paxil, and soon her life transformed into a psychiatric nightmare.

She began cutting herself regularly, and at one point, she used an

electric saw to take off the middle finger on her left hand. The Paxil

gave way to cocktails of Klonopin, Depakote, Zyprexa, and other

medications, and during a nearly four-year stay in a psych hospital,

she ended up on a cocktail of fifteen or so drugs, so doped up she

didn't even know where she was. "I don't know the exact date,"

Jenna says, summing up this history, "but slowly my speech and my

walking and my balance and the shaking got really bad at that hos¬

pital. And they just kept on adding drugs. That's how f-f-f-fucked

up they are.”

Today, Jenna's psychiatric problems remain severe. On the day

we met, her wrist was bandaged, as she had recently tried to cut her¬

self, and thus the medications haven't been much help in that re¬

gard, either. But, she says, "I don't see anything different happening.

I have brought up the issue of taking me off the meds billions of

times."

Before we left our sidewalk table, Chris provided me with the de¬

tails of Jenna's daily cocktail: two antidepressants, an antipsychotic,

a benzodiazepine, a Parkinson's medication, and three others for

physical problems likely related to the psychiatric drugs. Later, I cal¬

culated that even if generics were prescribed whenever possible, she

was consuming $800 of medication monthly, or roughly $10,000

annually. She had been on psychiatric medications for twelve years,

which meant that her Rx bill for psychiatric medications might al¬

ready have surpassed $100,000, and given that she will likely

remain on the drugs for the rest of her life, this bill could eventually

end up well north of $200,000.

"They are making a lot of money on me," Jenna says. "But these

drugs have ruined my life. They make me all f-f-f-fucked up.”

316

ANATOMY OF AN EPIDEMIC

A Business Triumph

Jenna's perspective on her care was not an unusual one. Many of

the people on SSI and SSDI that I interviewed spoke about how they

felt they were caught in the tangles of a business enterprise. "There

is a reason we are called consumers" was a comment I heard several

times. They are right of course that the pharmaceutical companies

want to build a market for their products, and when we view the

psychopharmacology "revolution" through this prism, as a business

enterprise first and a medical enterprise second, we can easily see

why psychiatry and the pharmaceutical companies tell the stories

they do, and why the studies detailing poor long-term outcomes

have been kept from the public. That information would derail a

business enterprise that brings profits to so many.

As we saw earlier, during the late 1970s psychiatry was worried

about its survival. The public viewed its therapies as "low in effi¬

cacy," and sales of psychiatric drugs were in decline. Then, in what

might be called a "rebranding” effort, psychiatry published DSM-

III and began telling the public that mental disorders were "real"

diseases, just like diabetes and cancer, and that their drugs were

chemical antidotes to those diseases, just like "insulin for diabetes."

That story, while it may have been false in kind, created a powerful

conceptual framework for selling psychiatric medications of all

types. Everyone could understand the chemical-imbalance metaphor,

and once the public came to understand that notion, it became

relatively simple for pharmaceutical companies and their story¬

telling allies to build markets for psychiatric drugs of various types.

They ran "educational" campaigns to make the public more

"aware” of the various disorders the drugs were approved to treat,

and, at the same time, they expanded the diagnostic boundaries of

mental disorders.

After Prozac was introduced, NIMH's DART campaign informed

the public that depression regularly went "undiagnosed and un¬

treated.” Upjohn partnered with the APA to tell the public that

"panic disorder" was a common affliction. In 1990, the NIMH

launched its "Decade of the Brain,” telling the public that 20

TALLYING UP THE PROFITS

317

percent of Americans suffered from mental disorders (and thus

might be in need of psychiatric medications). Soon psychiatric groups

and others were promoting "screening programs," which from a

business perspective are best described as customer-recruitment ef¬

forts. NAMI, for its part, understood that its "educational" efforts

served a commercial end, writing in a 2000 document filed with the

government that "providers, health plans, and pharmaceutical com¬

panies want to grow their markets and to increase their share of the

market. . . . NAMI will cooperate with these entities to grow the

market by making persons aware of the issues involving severe

brain disorders." 2

The APA is in charge of defining diagnostic categories in our so¬

ciety, and DSM-IV, an 886-page tome published in 1994, listed 297

disorders, 32 more than DSM-III. New and expanded diagnoses in¬

vite more people into the psychiatric drugstore, and one of the best

examples of this type of market-building occurred in 1998, when

GlaxoSmithKline got the FDA to approve Paxil for "social anxiety

disorder." In the past, this might have been perceived as a character

trait (shyness), but GlaxoSmithKline hired a PR firm, Cohn & Wolfe,

to promote awareness of this newly recognized "disease,” and soon

newspapers and television shows were telling of how SAD afflicted

13 percent of the American population, making it "the third most

common psychiatric disorder in the United States, after depression

and alcoholism." Those afflicted with this illness, the public learned,

were in some ways biologically "allergic to people." 3

Diagnostic changes lay behind the bipolar boom, too. In DSM-III

(1980), bipolar illness was identified for the first time (the old manic-

depressive cohort was splintered into different groups), and then

psychiatry steadily loosened the diagnostic boundaries for this ill¬

ness, such that today the field talks about bipolar I, bipolar II, and a

"bipolarity intermediate between bipolar disorder and normality."

This once rare disease is now said to afflict 1 to 2 percent of the adult

population, and if the "intermediate” bipolar folk are counted, 6

percent. As this diagnostic expansion happened, pharmaceutical

companies and their allies mounted their usual "educational" cam¬

paigns. Abbott Laboratories and NAMI teamed up to promote

a "Bipolar Awareness Day"; in 2002, Eli Lilly joined with the De-

31 8

ANATOMY OF AN EPIDEMIC

pression and Bipolar Support Alliance to launch a new online desti¬

nation, bipolarawareness.com . Today many websites offer visitors a

quick question-and-answer test to see if they have this illness.

Naturally, pharmaceutical companies want to sell their drugs to

people of all ages, and they built the pediatric market for psy¬

chotropics step by step. First, in the 1980s, the prescribing of stimu¬

lants to "hyperactive” children took off. Next, in the early 1990s,

psychiatrists began regularly prescribing SSRIs to teenagers. But

that meant prepubertal children weren't being prescribed these new

wonder drugs, and in 1997, the Wall Street Journal reported that

the manufacturers of SSRIs were "taking aim at a controversial new

market: children." The drug firms were "preparing their medica¬

tions in easy-to-swallow forms that will be more palatable to even

the youngest tykes," the newspaper said, with Eli Lilly formulating

a "minty liquid” Prozac for the tots to down.* The New York

Times, in its coverage of this initiative, explained quite clearly what

was driving it: "The adult market for [SSRIs] has become satu¬

rated. . . . The companies are looking for expanded markets." 5

Psychiatry quickly provided a medical cover for this marketing ef¬

fort, with the American Academy of Child and Adolescent Psychia¬

try announcing that 5 percent of all children in the United States

were clinically depressed. "Many of these young patients now are

inadequately treated, experts say, often leading to long-term emo¬

tional and behavioral problems, drug abuse, or even suicide," the

Wall Street Journal reported.*

The creation of the "juvenile bipolar” market was a bit more

complicated. Prior to the 1990s, psychiatry thought that bipolar ill¬

ness simply didn't occur in prepubertal children, or was extremely

rare. But children and teenagers prescribed stimulants and anti¬

depressants often suffered manic episodes, and thus pediatricians

and psychiatrists began to see more youth with "bipolar" symptoms.

At the same time, once Janssen and Eli Lilly brought their atypical

antipsychotics to market, they were looking for a way to sell those

drugs to children, and during the mid-1990s, Joseph Biederman at

Massachusetts General Hospital in Boston provided the diagnostic

framework that made that possible. In 2009, while being deposed in

a legal case, he explained his handiwork.

TALLYING UP THE PROFITS

319

All psychiatric diagnoses, he said, "are subjective in children and

in adults." As such, he and his colleagues decided that children who

in the past had been seen as having pronounced behavioral prob¬

lems should instead be diagnosed with juvenile bipolar illness. "The

conditions that we see in front of us are reconceptualized," Bieder-

man testified. "These children have been called in the past conduct

disorder, oppositional-defiant disorder. It's not that these children

did not exist, they were just under different names." 7 Biederman

and his colleagues decided that "severe irritability" or "affective

storms" would be the telltale signs of juvenile bipolar disorder, and

with this new diagnostic criteria in hand, they announced in 1996

that many children diagnosed with ADHD were in fact "bipolar" or

else "comorbid” for both illnesses. 8 The illness was a "much more

common condition than was previously thought,” often appearing

when children were only four or five years old, Biederman said.*’

Soon parents in the United States were reading newspaper articles

about this newly recognized illness and buying The Bipolar Child, a

book published by Random House in 2000. Child psychiatrists,

meanwhile, began treating it with atypical antipsychotics.

That was the marketing machinery that lured more and more

Americans into the psychiatric drugstore. As new drugs were

brought to market, disease "awareness" campaigns were conducted

and diagnostic categories were expanded. Now, once a business gets

a customer into its store, it wants to keep that customer and get that

customer to buy multiple products, and that's when the psychiatric

"drug trap” kicks in.

The "broken brain" story helps with customer retention, of

course, for if a person suffers a "chemical imbalance," then it makes

sense that he or she will have to take the medication to correct it in¬

definitely, like "insulin for diabetes.” But more important, the drugs

create chemical imbalances in the brain, and this helps turn a first¬

time customer into a long-term user, and often into a buyer of mul¬

tiple drugs. The patient's brain adapts to the first drug, and that

* During Biederman's February 26, 2009, deposition, an attorney asked him

about his rank at Harvard Medical School. "Full professor," he replied.

"What's above that?" the attorney asked. "God," Biederman replied.

3 20 • ANATOMY OF AN EPIDEMIC

makes it difficult to go off the medication. The store's exit door is

hard to squeeze through, so to speak. At the same time, since

psychiatric drugs perturb normal function, they regularly cause

physical and psychiatric problems, and this greases the path to

polypharmacy. The hyperactive child is put on a stimulant that

rouses him during the day; at night he needs a sleeping pill to go to

sleep. An atypical causes people to feel depressed and lethargic; psy¬

chiatrists may prescribe an antidepressant to treat that problem.

Conversely, an antidepressant may stir a bout of mania; in that case

an atypical antipsychotic may be prescribed to tamp down the

mania. The first drug triggers a need for a second, and so on.

Eli Lilly even capitalized on this fact when it brought Zyprexa to

market. As it well knew, Prozac and other SSRIs could trigger manic

episodes, and so it instructed its sales representatives to tell psychia¬

trists that Zyprexa "is a great mood stabilizer, especially for pa¬

tients whose symptoms were aggravated by an SSRI." 10 In essence,

Eli Lilly was telling doctors to prescribe its second drug to fix the

psychiatric problems caused by its first one. We can also see this

cascading effect operating at a societal level. The SSRIs came to

market and suddenly bipolar patients were cropping up every¬

where, and then this new group of patients provided a market for

the atypicals.*

All of this has produced a growth industry of impressive dimen¬

sions. In 1985, outpatient sales of antidepressants and antipsychotics

in the United States amounted to $503 million.” Twenty-three years

later, U.S. sales of antidepressants and antipsychotics reached $24.2

billion, nearly a fiftyfold increase. Antipsychotics —a class of drugs

previously seen as extremely problematic in kind, useful only in se¬

verely ill patients —were the top revenue-producing class of drugs in

2008, ahead even of the cholesterol-lowering agents. 12 Total sales of

all psychotropic drugs in 2008 topped $40 billion. Today —and this

* In a similar vein, pharmaceutical companies have pounced on the fact that

many of the drugs initially prescribed for a target symptom don't work very

well. "Two out of three people treated for depression still have symptoms," a

Bristol-Myers Squibb commercial informed television viewers in 2009. The

solution? Add an atypical antipsychotic. Ability, to the mix.

TALLYING UP THE PROFITS

• 321

shows how crowded the drugstore has become —one in every eight

Americans takes a psychiatric drug on a regular basis. 13

The Money Tree

Naturally, this flourishing business enterprise generates great per¬

sonal wealth for executives at pharmaceutical companies, and

money also flows in fairly copious amounts to the academic psychi¬

atrists who tout their drugs. Indeed, the profits from this enterprise

trickle down to nearly all of those who tell the "psychiatric drugs

are good” story to our society. To get a sense of the amounts in¬

volved, we can look at the money that the different players in this

enterprise receive.

We can start with Eli Lilly, as it serves as a good example of the

profits that go to a drug company's shareholders and its executives.

Eli Lilly

In 1987, Eli Lilly's pharmaceutical division generated $2.3 billion in

revenues. The company did not have a central nervous system drug

of any importance, as its three bestselling drugs were an oral anti¬

biotic, a cardiovascular drug, and an insulin product. Eli Lilly began

selling Prozac in 1988, and four years later it became the company's

first billion-dollar drug. In 1996, Eli Lilly brought Zyprexa to mar¬

ket, and it became a billion-dollar drug in 1998. By 2000, these two

drugs accounted for nearly half of the company's revenues of $10.8

billion.

Prozac soon after lost its patent protection, and thus the wealth¬

generating effects of the two drugs can best be assessed across a

thirteen-year period, from 1987 to 2000. During this time, Eli

Lilly's value on Wall Street rose from $10 billion to $90 billion. An

investor who bought $10,000 of Eli Lilly stock in 1987 would have

seen that investment grow to $96,850 in 2000, and along the way

the investor would have received an additional $9,720 in dividends.

At the same time, Eli Lilly's executives and employees, in addition

322

ANATOMY OF AN EPIDEMIC

to their salaries and bonuses, netted around $3.1 billion from the

stock options they exercised.' 4

Academic psychiatrists

The pharmaceutical companies would not have been able to build a

$40 billion market for psychiatric drugs without the help of psychi¬

atrists at academic medical centers. The public looks to doctors for

information about illnesses and how best to treat them, and so it

was the academic psychiatrists —paid by drug companies to serve as

consultants, on advisory boards, and as speakers —who in essence

acted as the salesmen for this enterprise. The pharmaceutical com¬

panies, in their internal memos, accurately call these psychiatrists

"key opinion leaders," or KOLs for short.

Thanks to a 2008 investigation by Iowa senator Charles Grass-

ley, the public got a glimpse of the amount of money that the phar¬

maceutical companies pay their KOLs. The academic psychiatrists

regularly receive federal NIH grants, and as such, they are required

to inform their institutions how much they receive from pharma¬

ceutical companies, with the medical schools expected to manage

the "conflict of interest” whenever this amount exceeds $10,000

annually. Grassley investigated the records of twenty or so academic

psychiatrists, and he found that not only were many making much

more than $10,000 a year, they were also hiding this fact from their

schools.

Here are a few examples of the money paid to KOLs in psy¬

chiatry.

• From 2000 to 2007, Charles Nemeroff, chair of the psychia¬

try department at Emory Medical School, earned at least

$2.8 million as a speaker and consultant for drug firms, with

GlaxoSmithKline alone paying him $960,000 to promote

Paxil and Wellbutrin. He is a coauthor of the APA's Textbook

of Psychopharmacology, which is the bestselling textbook in

the field. He also wrote a trade book about psychiatric med¬

ications, The Peace of Mind Prescription, for the general

public. He has served on the editorial boards of more than

sixty medical journals and for a time was editor in chief of

TALLYING UP THE PROFITS

323

Neuropsychopharmacology. In December of 2008, he re¬

signed as chair of Emory's psychiatry department, as he had

failed to inform Emory of his drug-company paychecks. 15

Zachary Stowe, also a professor of psychiatry at Emory, re¬

ceived $250,000 from GlaxoSmithKline in 2007 and 2008,

partly to promote the use of Paxil by breast-feeding women.

Emory "reprimanded” him for failing to properly disclose

these payments to the school. 16

Another member of GlaxoSmithKline's speaker bureau was

Frederick Goodwin, a former director of the NIMH. The

company paid him $1.2 million from 2000 to 2008, mostly

to promote the use of mood stabilizers for bipolar illness

(GlaxoSmithKline sells Lamictal, which is a mood stabilizer).

Goodwin is the coauthor of Manic-Depressive Illness, the au¬

thoritative textbook on this disorder, and he also was the

longtime host of a popular radio show, The Infinite Mind,

which was carried on NPR stations nationwide. His show

regularly featured discussions of psychiatric medications,

with Goodwin, in a program broadcast on September 20,

2005, warning that if children with bipolar disorder were not

treated, they could suffer brain damage. Goodwin has been a

speaker or consultant for a number of other pharmaceutical

companies; the $1.2 million was what he received from Glaxo¬

SmithKline alone. In an interview with the New York Times,

Goodwin explained that he was only "doing what every

other expert in the field does." 17

From 2000 to 2005, Karen Wagner, director of child and

adolescent psychiatry at the University of Texas, collected

more than $160,000 from GlaxoSmithKline. She promoted

the use of Paxil in children, and did so in part by coauthoring

an article that falsely reported the results of a pediatric trial

of the drug.

In a confidential document written in October 1998, Glaxo¬

SmithKline concluded that in the study, Paxil "failed to

demonstrate a statistically significant difference from placebo

on the primary efficacy measures." 15 In addition, five of the

ninety-three adolescents treated with Paxil in the study

324

ANATOMY OF AN EPIDEMIC

suffered "extreme lability," versus one in the placebo group,

which meant that the drug markedly elevated the suicide risk.

The study had shown Paxil to be neither safe nor effective in

adolescents. However, in a 2001 article published in the Jour¬

nal of the American Academy of Child & Adolescent Psychi¬

atry, Wagner and twenty-one other leading child psychiatrists

stated that the study proved that Paxil is "generally well tol¬

erated and effective for major depression in adolescents." 19

They did not discuss the sharply elevated suicide risk, writing

instead that only one child treated with Paxil had suffered

a serious adverse event, with that child developing a "head¬

ache.” New York State attorney general Eliot Spitzer sued

GlaxoSmithKline for fraudulently marketing Paxil to adoles¬

cents, a case which was settled out of court.

All told, Wagner has been a consultant or advisor to at

least seventeen pharmaceutical companies. The $160,000

was the amount she received from GlaxoSmithKline alone;

she told her school that she had received $600. 20

From 1999 to 2006, Jeffrey Bostic, a psychiatrist at Massa¬

chusetts General Hospital in Boston, collected more than

$750,000 from Forest Laboratories to promote the prescrib¬

ing of Celexa and Lexapro to children and adolescents. He

gave more than 350 talks in twenty-eight states during this

period, leading one Forest sales rep to boast: "Dr. Bostic is

the man when it comes to child psych!" 21 In March of 2009,

the federal government charged Forest with illegally market¬

ing these drugs to this patient population, alleging that it had

paid "kickbacks, including lavish meals and cash payments

disguised as grants and consulting fees, to induce doctors to

prescribe the drugs.” Dr. Bostic, the federal government said,

served as the company's "star spokesman" in this scheme.

The federal government noted that the company had also

failed to disclose the results of a study of these drugs in

children that had produced "negative” results.

From 2003 to 2007, Melissa DelBello, an associate professor

of psychiatry at the University of Cincinnati, received at least

$418,000 from AstraZeneca. She promoted the prescribing

TALLYING UP THE PROFITS

325

of atypical antipsychotics, including AstraZeneca's Seroquel,

to juvenile bipolar patients. DelBello worked for at least

seven other pharmaceutical companies. "Trust me, I don't

take much” from drug firms, she told the New York Times

prior to Grassley's report. 22

• Joseph Biederman may have been the KOL who did the most

to help the pharmaceutical industry build a market for its

products. To a large extent, juvenile bipolar illness was his

creation, and children and adolescents so diagnosed are often

treated with drug cocktails. Pharmaceutical companies paid

him $1.6 million for his various services from 2000 to 2007,

with much of this money coming from Janssen, the division

of Johnson &c Johnson that sells Risperdal. 23

Biederman also got the company to pay $2 million from

2002 to 2005 to create the Johnson &C Johnson Center for Pe¬

diatric Psychopathology at Massachusetts General Hospi¬

tal. 24 In a 2002 report on the center, he candidly set forth its

aims. The center, he explained, was a "strategic collabora¬

tion" that would "move forward the commercial goals of

J&J.” He and his colleagues would develop screening tests

for juvenile bipolar illness, and then teach CME (continuing

medical education) courses to train pediatricians and psychi¬

atrists to use them. Their research, Biederman wrote, would

"alert physicians to the existence of a large group of children

who might benefit from treatment with Risperdal.” In addi¬

tion, the center would promote the understanding that "pedi¬

atric mania evolves into what some have called mixed or

atypical mania in adulthood, [which] will provide further

support for the chronic use of Risperdal from childhood

through adulthood.'" 1 ' In the past, Biederman noted, he had

successfully led the medical profession to conceive of ADHD

* Biederman here is describing the course of children who are diagnosed with

bipolar illness and then medicated; those children do tend to become chroni¬

cally ill in the way he describes. But there is no medical literature showing that

there is a disease that takes this course in unmedicated children.

326

ANATOMY OF AN EPIDEMIC

as a ''chronic” illness, and now he would do the same for

bipolar disorder. 25

Biederman has been the Pied Piper of pediatric bipolar

illness in our society, and in this document we can see the

future that he was laying out for the children given this diag¬

nosis. They were being groomed to be lifelong consumers of

psychiatric medications. The child diagnosed with bipolar

disorder would be put on an antipsychotic, and that child

could then be expected to become chronically ill, and that

would require a lifetime of "aggressive treatments such as

Risperdal.” Perhaps there is a file tucked away in a drug com¬

pany cabinet that estimates the expected lifetime consump¬

tion of psychiatric medications by a child diagnosed with

bipolar illness; all we can say, in this book, is that every child

so diagnosed is, from a business standpoint, a new Jenna.

The next tier down

The KOLs are the "stars" of the field, as they are the ones who "in¬

fluence” their peers at a national and international level, but the

pharmaceutical companies also pay physicians to promote their

drugs on a more local basis, with these speakers giving talks at din¬

ners or to other physicians in their offices. Pay typically starts at

$750 per event and rises from there. Two states, Minnesota and

Vermont, have passed "sunshine” laws that disclose these pay¬

ments, and their reports provide insight into the flow of money to

these doctors.

In 2006, pharmaceutical firms gave $2.1 million to Minnesota

psychiatrists, up from $1.4 million in 2005. From 2002 to 2006, the

recipients of drug-company money included seven past presidents of

the Minnesota Psychiatric Society and seventeen faculty psychia¬

trists at the University of Minnesota. John Simon, who was a mem¬

ber of the state's Medicaid formulary committee, which guides the

state's spending on drugs, was the top-paid psychiatrist, earning

$570,000 for his services to drug companies. All told, 187 of 571

psychiatrists in Minnesota received pharmaceutical money for some

reason or other during this period, a percentage that was "much

TALLYING UP THE PROFITS

327

higher” than for any other specialty. Their collective take was $7.4

million. 26

Vermont's reports tell much the same story. Of all the medical

specialties, psychiatry received the most money from the drug

companies.

The community psychiatrist

The pharmaceutical companies also provide freebies to community

psychiatrists. They invite them to free dinners where the KOLs and

the local experts give their talks, and their sales representatives reg¬

ularly come to their offices bearing small gifts. "Gave Dr. Child a

cupcake sized peanut butter cup,” wrote an Eli Lilly sales represen¬

tative, in a 2002 report to her boss. "He was kind of tickled.” Or as

she said after another sales call: "Doc and staff loved the goodie

box I brought in, filled with useful items for their new clinic." 22

These are very small bribes, but even a small gift helps build a social

bond. A California group surveyed the drug firms and found that

they do set a limit on the freebies that are offered to a psychiatrist

each year; GlaxoSmithKline's was $2,500 per physician, while Eli

Lilly's was $3,000. There are many companies that sell psychiatric

drugs, and thus any psychiatrist who welcomes sales reps can enjoy

a regular supply of goodies.

NAMI and all the rest

Eli Lilly now posts on the Web a list of the "educational" and "phil¬

anthropy" grants it makes, and this provides a peek at the money

going to patient advocacy groups and various educational organiza¬

tions. In the first quarter of 2009 alone, Eli Lilly gave $551,000 to

NAMI and its local chapters, $465,000 to the National Mental

Health Association, $130,000 to CHADD (an ADHD patient-

advocacy group), and $69,250 to the American Foundation for Sui¬

cide Prevention. The company gave more than $1 million to various

educational organizations, including $279,533 to the Antidote Ed¬

ucation Company, which runs a "continuing medical education"

course. Those are the amounts from one pharmaceutical company

328

ANATOMY OF AN EPIDEMIC

for three months; any full accounting of the flow of money to

patient advocacy groups and educational organizations would re¬

quire adding up the grants from all of the makers of psychiatric

drugs. 28

We All Pay the Tab

According to a 2009 report by the federal Agency for Healthcare

Research and Quality, spending on mental health services is now

rising at a faster rate than for any other medical category. 28 In 2008,

the United States spent about $170 billion on mental health ser¬

vices, which is twice the amount it spent in 2001, and this spending

is projected to increase to $280 billion in 2015. The public,

primarily through its Medicaid and Medicare programs, picks up

close to 60 percent of the nation's spending on mental health

services. 30

Such is the story of the psychiatric drug business. The industry

has excelled at expanding the market for its drugs, and this gener¬

ates a great deal of wealth for many. However, this enterprise has

depended on the telling of a false story to the American public, and

the hiding of results that reveal the poor long-term outcomes with

this paradigm of care. It also is exacting a horrible toll on our soci¬

ety. The number of people disabled by mental illness during the past

twenty years has soared, and now this epidemic has spread to our

children. Indeed, millions of children and adolescents are being

groomed to be lifelong users of these drugs.

From a societal and moral point of view, that is a bottom-line

that cries out for change.

Part Five

Solutions

Blueprints for Reform

I think it is time for another hunger strike.

- VINCE BOEHM, 2009

On July 28, 2003, six "psychiatric survivors" associated with

MindFreedom International, a patients' rights organization, an¬

nounced a "fast for freedom.” David Oaks, Vince Boehm, and four

others sent a letter to the American Psychiatric Association, NAMI,

and the U.S. Office of the Surgeon General stating that they would

begin a hunger strike unless one of the organizations provided "sci¬

entifically valid evidence" that the various stories they told to the

public about mental disorders were true. Among other things, the

MindFreedom group asked for evidence proving that major mental

illness are "biologically-based brain diseases," and for evidence that

"any psychiatric drug can correct a chemical imbalance" in the

brain. The MindFreedom Six had put together a scientific panel to

review the organizations' replies, an advisory group that included

Loren Mosher, and they demanded that if the APA and the others

couldn't provide such scientific evidence, "you publicly admit to

media, government officials, and the general public that you are un¬

able to do so.” 1

Here's how the APA responded: "The answers to your questions

are widely available in the scientific literature, and have been for

years,” wrote medical director James Scully. He suggested that they

read the U.S. Surgeon General's 1999 Mental Health report, or an

332

ANATOMY OF AN EPIDEMIC

APA textbook coedited by Nancy Andreasen. "This is a 'user-

friendly' textbook for persons just being introduced to the field of

psychiatry," he explained. 2

Only the uneducated, it seemed, asked such dumb questions. But

Scully had failed to list any citations, and so the six "psychiatric sur¬

vivors" began their hunger strike, and when their scientific advisors

reviewed the texts that Scully had referred them to, they found no

citations there, either. Instead, the texts all grudgingly acknowl¬

edged the same bottom line. "The precise causes [etiology] of men¬

tal disorders are not known," U.S. surgeon general Satcher

confessed in his 1999 report. MindFreedom's scientific panel, in its

August 22 reply to Scully, observed that the strikers had asked

"clear questions about the science of psychiatry," and yet the APA

had brushed them off. "By not giving specific answers to the specific

questions posed by the hunger strikers, you appear to be affirming

the very reason for the hunger strike." 3

The APA never answered that letter. Instead, after the Mind-

Freedom group broke their fast (several started to have health prob¬

lems), it issued a press release, stating that the APA, NAMI, and the

rest of the psychiatric community "will not be distracted by those

who would deny that serious mental disorders are real medical con¬

ditions that can be diagnosed accurately and treated effectively." 4

But it was clear to all observers who had won this battle. The strik¬

ers had called the APA's bluff, and the APA had come up empty. It

hadn't come up with a single citation that supported the "brain dis¬

ease” story it told to the public. The MindFreedom Six, along with

their scientific panel, then issued a clarion call for help:

We urge members of the public, journalists, advocates, and of¬

ficials reading this exchange to ask for straightforward an¬

swers to our questions from the APA. We also ask Congress to

investigate the mass deception that the "diagnosis and treat¬

ment of mental disorders,” as promoted by bodies such as the

APA and its powerful allies, represents in America today. 5

The strike, noted MindFreedom executive director David Oaks,

stirred articles in the Washington Post and the Los Angeles Times.

BLUEPRINTS FOR REFORM

333

"The purpose of the strike was to educate the public. It was about

empowering the public and getting them to talk about these issues,

which affect everyone. It was about challenging the corporate bully¬

ing of the [public] mind." 6

Lessons from a Hunger Strike

When I first thought about writing a "solutions" chapter, I figured

that I would simply report on programs, both in the United States

and abroad, that involve using psychiatric medications in a selec¬

tive, cautious manner (or not at all), and are producing good re¬

sults. But then I thought of the hunger strike, and I realized that the

MindFreedom group had precisely identified the bigger issue at

hand.

The real question regarding psychiatric medications is this: When

and how should they be used? The drugs may alleviate symptoms

over the short term, and there are some people who may stabilize

well over the long term on them, and so clearly there is a place for

the drugs in psychiatry's toolbox. However, a "best" use paradigm

of care would require psychiatry, NAMI, and the rest of the psychi¬

atric establishment to think about the medications in a scientifically

honest way and to speak honestly about them to the public. Psychi¬

atry would have to acknowledge that the biological causes of men¬

tal disorders remain unknown. It would have to admit that the

drugs, rather than fix chemical imbalances in the brain, perturb the

normal functioning of neurotransmitter pathways. It would have to

stop hiding the results of long-term studies that reveal that the med¬

ications are worsening long-term outcomes. If psychiatry did that, it

could figure out how to use the medications judiciously and wisely,

and everyone in our society would understand the need for alterna¬

tive therapies that don't rely on the medications or at least minimize

their use.

In his 1992 book How to Become a Schizophrenic, John

Modrow —who had been so diagnosed —wrote the following:

"How then are we to help 'schizophrenics'? The answer is simple:

334

ANATOMY OF AN EPIDEMIC

Stop the lies!" 7 In essence, that’s what the MindFreedom Six were

demanding, and as their advisory panel observed, this is a perfectly

rational request. And that, I think, sums up the challenge that we, as

a society, now face. How do we break up the psychiatry-and-drug-

company partnership that, as we have seen, regularly does lie to us?

How can we insist that our society's mental health system be driven

by honest science rather than by a partnership that is constantly

seeking to expand the market for psychiatric drugs?

There is no easy answer to that question. But clearly our society

needs to have a conversation about it, and so I thought that the rest

of this "solutions" chapter should be devoted to interviews and in¬

vestigations of alternative programs that could help make that

conversation a fruitful one.

An Artful Form of Care

David Healy is a professor of psychiatry at Cardiff University and

tends to psychiatric patients at the District General Hospital in

North Wales, where he has been since 1990. His office is located a

few feet from a closed ward, and naturally, he regularly prescribes

psychiatric medications. Indeed, although he has come to be per¬

ceived by many in psychiatry as a "maverick,” he recoils at that

word. In the 1980s, he notes, he researched serotonin reuptake in

depressed patients. He participated as a clinical investigator in a

trial of Paxil. He has authored more than a dozen books and pub¬

lished more than 120 articles, with much of his writing focusing on

the history of psychiatry and the psychopharmacology era. His CV

speaks of a psychiatrist and historian who, until he began writing

about problems with the SSRIs, was embraced by the psychiatric es¬

tablishment. "I don't think I've changed much at all," he said. "I

think the mainstream has left me." 8

His thoughts on how psychiatric drugs should be used (and what

they really do) have been deeply influenced both by his writings on

the history of psychiatry and by a study he has conducted that

BLUEPRINTS FOR REFORM

335

compares outcomes of the mentally ill in North Wales a century ago

with outcomes in the region today. The population hasn't changed

in this period, with around 240,000 in the area, and whereas all the

seriously mentally were treated at the North Wales Asylum in Den¬

bigh a century ago, today all psychiatric patients needing to be hos¬

pitalized are treated at the District General Hospital in Bangor. By

poring over records of the two institutions, Healy and his assistants

have been able to determine the number of people who were treated

back then and the number treated today, as well as the frequency of

their hospitalizations.

The common belief, Healy notes, is that the old asylums were

bulging with lunatics. Yet from 1894 to 1896, there were only

forty-five people per year admitted to the North Wales Asylum (for

mental problems). Furthermore, as long as the patients didn't suc¬

cumb to tuberculosis or some other infectious disease, they regu¬

larly got better over the course of three months to a year and went

home. Fifty percent were discharged as "recovered” and another 30

percent as "relieved.” In addition, the overwhelming majority of

patients admitted for a first episode of illness were discharged and

never again rehospitalized, and that was true even for psychotic pa¬

tients. This latter group averaged only 1.23 hospitalizations in a

ten-year period (that number includes the initial hospitalization).

Today, the assumption is that patients fare much better than they

used to thanks to psychiatric medications. However, in 1996, there

were 522 people admitted to the psychiatric ward at the District

General Hospital in Bangor —nearly twelve times the number ad¬

mitted to the Denbigh asylum a century earlier. Seventy-six percent

of the 522 patients had been there before, part of a large group of

patients in North Wales that cycle regularly through the hospital.

Although the patients spent a shorter time in the hospital than they

did in 1896, only 36 percent were discharged as recovered. Finally,

the patients admitted for a first episode of psychosis in the 1990s

averaged 3.96 hospitalizations over the course of ten years —more

than three times the number a century earlier. Patients today are

clearly more chronically ill than they were a century ago, with mod¬

ern treatments apparently having set up a "revolving door." 9

336

ANATOMY OF AN EPIDEMIC

"We have been surprised by how poor the five-year outcomes are

today,” Healy said. "Each time we look at the current data, at the

first batch of five-year outcomes [for a particular diagnostic group],

we think, 'God, that can't be the case.' "

Their study sends a fairly clear message about how and when

psychiatric medications should be used. "A bunch of people used to

recover,” Healy explained, but if you immediately put all patients

on medications, you run the risk of "giving them a chronic problem

they wouldn't have had in the old days.” Healy now tries to "watch

and wait" before giving psychiatric drugs to first-episode patients,

as he wants to see if this type of natural recovery can take hold. "I

try to use the drugs cautiously in reasonably low doses, and I tell the

patient, 'If the drug isn't doing what we want it to do, we are going

to halt it,' " he said. If psychiatrists listened to their patients about

how the drugs were affecting them, he concluded, "we would have

only a few patients on them long-term.”

There it is: a simple prescription for using the medications judi¬

ciously. Once a physician realizes that many people who experience

a bout of psychosis or a deep depression can recover naturally, and

that long-term use of psychotropics is associated with increased

chronicity, then it becomes apparent that the drugs need to be used

in a selective, limited manner. Healy has seen this approach work

with his patients, many of whom initially insist that they need the

drugs. "I say to them, 'We can do more harm than good,' " he said.

"They don't realize just how much harm we can do."

Healing the "In-Between"

For a long time, western Lapland in Finland had one of the highest

rates of schizophrenia in Europe. There are about 70,000 people

who live there, and during the 1970s and early 1980s, twenty-five

or so new cases of schizophrenia appeared each year —an incidence

rate double and even triple the norm for other parts of Finland and

the rest of Europe. Furthermore, those patients regularly became

BLUEPRINTS FOR REFORM

337

chronically ill. But today the long-term outcomes of psychotic pa¬

tients in western Lapland are the best in the Western world, and this

region now sees very few new cases of schizophrenia.

This is a medical success that has been decades in the making,

and it began in 1969 when Yrjo Alanen, a Finnish psychiatrist who

had psychoanalytic training, arrived at the psychiatric hospital in

Turku, a port city in southwest Finland. At that time, few psychia¬

trists in the country thought that psychotherapy could help schizo¬

phrenics. However, Alanen believed that the hallucinations and

paranoid utterances of schizophrenic patients, when carefully

parsed, told meaningful stories. Hospital psychiatrists, nurses, and

staff needed to listen to the patients. "It's almost impossible for any¬

one meeting with these patients' families to not understand that

they have difficulties in life," Alanen explained in an interview at

the psychiatric hospital in Turku. They are "not ready" to be adults,

and "we can help with this development." 10

Over the next fifteen years, Alanen and a handful of other Turku

psychiatrists, most notably Jukka Aaltonen and Viljo Rakkolainen,

created what they called the "need-adapted” treatment of psychotic

patients. Since psychotic patients are a very heterogeneous group,

they decided that treatment needed to be "case specific.” Some first-

episode patients would need to be hospitalized, and others would

not. Some would benefit from low doses of psychiatric medications

(either benzos or neuroleptics), and others would not. Most impor¬

tant, the Turku psychiatrists settled on group family therapy —of a

particularly collaborative type —as the core treatment. Psychiatrists,

psychologists, nurses, and others trained in family therapy all

served on two- and three-member "psychosis teams," which would

meet regularly with the patient and his or her family. Decisions

about the patient's treatment were made jointly at those meetings.

In those sessions, the therapists did not worry about getting the

patient's psychotic symptoms to abate. Instead, they focused the

conversation on the patient’s past successes and achievements, with

the thought that this would help strengthen his or her "grip on life.”

The hope, said Rakkolainen, "is that they haven't lost the idea that

they can be like others." The patient might also receive individual

338 •

ANATOMY OF AN EPIDEMIC

psychotherapy to help this process along, and eventually the patient

would be encouraged to construct a new "self-narrative” for going

forward, the patient imagining a future where he or she was inte¬

grated into society, rather than isolated from it. "With the biological

conception of psychosis, you can't see the past achievements" or the

future possibilities, Aaltonen said.

During the 1970s and 1980s, the outcomes for psychotic patients

in the Turku system steadily improved. Many chronic patients

were discharged from the hospital, and a study of first-episode

schizophrenic-type patients treated from 1983 to 1984 found that

61 percent were asymptomatic at the end of five years and only 18

percent were on disability. This was a very good result, and from

1981 to 1987, Alanen coordinated the Finnish National Schizo¬

phrenia Project, which determined that the need-adapted model of

care developed in Turku could be successfully introduced into other

cities. Two decades after Alanen and the others had initiated their

Turku project, Finland had decided that psychotherapy could in¬

deed help psychotic patients.

However, the question of the best use of antipsychotics remained,

and in 1992, Finland mounted a study of first-episode patients to

answer it. All six sites in the study provided the newly diagnosed

patients with need-adapted treatment, but in three of the centers,

the patients were not put on antipsychotics during the first three

weeks (benzos could be used), with drug therapy initiated only if the

patient hadn't improved during this period. At the end of two years,

43 percent of the patients from the three "experimental” sites had

never been exposed to neuroleptics, and overall outcomes at the ex¬

perimental sites were "somewhat better" than they were at the

centers where nearly all of the patients had been exposed to the

drugs. Furthermore, among the patients at the three experimental

sites, those who had never been exposed to neuroleptics had the

best outcomes. 11

"I would advise case-specific use [of the drugs],” Rakkolainen

said. "Try without antipsychotics. You can treat them better with¬

out medication. They become more interactive. They become them¬

selves." Added Aaltonen: "If you can postpone medication, that's

important."

BLUEPRINTS FOR REFORM

339

It might seem that Finnish psychiatry, given the outcomes of the

study, would have then embraced —on a national level —this "no

immediate use of neuroleptics" model of care. Instead, Alanen and

the other creators of need-adapted treatment retired, and during the

1990s, Finland’s treatment of psychosis became much more "bio¬

logically" oriented. Even in Turku, first-episode patients are regu¬

larly treated with antipsychotics today, and Finnish guidelines now

call for the patients to be kept on the drugs for at least five years

after a first episode. "I am a bit disappointed,” Alanen confessed at

the end of our interview.

Fortunately, one of the three "experimental" sites in the 1992-

1993 study did take the results to heart. And that site was Tornio, in

western Lapland.

On my way north to Tornio, I stopped to interview Jaakko Seikkula,

a professor of psychotherapy at the University of Jyvaskyla. In

addition to working at Keropudas Hospital in Tornio for nearly

twenty years, he has been the lead author on several studies docu¬

menting the extraordinary outcomes of psychotic patients in west¬

ern Lapland.

The transformation of care at Keropudas Hospital, from a sys¬

tem in which patients were regularly hospitalized and medicated to

one in which patients are infrequently hospitalized and only occa¬

sionally medicated, began in 1984, when Rakkolainen visited and

spoke about need-adapted treatment. The Keropudas staff, Seikkula

recalled, immediately sensed that holding "open meetings," where

every participant freely shared his or her thoughts, would provide

psychotic patients with a very different experience from conven¬

tional psychotherapy. "The language we use when the patient is sit¬

ting with us is so different from the language we use when we

(therapists] are by ourselves and discussing the patient,” he said.

"We do not use the same words, and we have to listen more to the

patient's ideas about what is going on, and listen more to the

family."

Eventually, Seikkula and others in Tornio developed what they

called open-dialogue therapy, which was a subtle variation of

340

ANATOMY OF AN EPIDEMIC

Turku's need-adapted model. As was the case in Turku, patient

outcomes in western Lapland improved during the 1980s, and then

Tornio was selected to be one of the three experimental sites in

Finland's 1992-93 first-episode study. Tornio enrolled thirty-four

patients, and at the end of two years, twenty-five had never been

exposed to neuroleptics. Nearly all of the never-medicated patients

in the national study (twenty-five of twenty-nine) had actually

come from this one site, and thus it was only here that hospital

staff observed the longer-term course of unmedicated psychosis.

And they found that while recovery from psychosis often pro¬

ceeds at a fairly slow pace, it regularly happens. The patients,

Seikkula said, "went back to their work, to their studies, to their

families." 12

Encouraged by the results, Keropudas Hospital immediately

started a new study, charting the long-term outcomes of all first-

episode psychotic patients in western Lapland from 1992 through

1997. At the end of five years, 79 percent of the patients were

asymptomatic and 80 percent were working, in school, or looking

for work. Only 20 percent were on government disability. Two-thirds

Five-Year Outcomes for First-Episode Psychotic Patients in Finnish

Western Lapland Treated with Open-Dialogue Therapy

Patients (N=75)

Schizophrenia (N=30)

Other psychotic disorders (N=45)

Antipsychotic use

Never exposed to antipsychotics

67 %

Occasional use during five years

33% /

Ongoing use at end of five years

20%

Psychotic symptoms

Never relapsed during five years

67%

Asymptomatic at five-year follow-up

79%

Functional outcomes at five years

Working or in school

73%

Unemployed

On disability

20%

Source: Seikkula, J. "Five-year experience of first-episode nonaffective psychosis in o pe n-d i al og u e

approach." Psychotherapy Research 16 (2006): 21 4-28.

BLUEPRINTS FOR REFORM

341

of the patients had never been exposed to antipsychotic medication,

and only 20 percent took the drugs regularly. 13 Western Lapland

had discovered a successful formula for helping psychotic patients

recover, with its policy of no immediate use of neuroleptics in first-

episode patients critical to that success, as it provided an "escape

valve” for those who could recover naturally.

"I am confident of this idea," Seikkula said. "There are patients

who may be living in a quite peculiar way, and they may have psy¬

chotic ideas, but they still can hang on to an active life. But if they

are medicated, because of the sedative action of the drugs, they lose

this 'grip on life,' and that is so important. They become passive,

and they no longer take care of themselves."

Today, the psychiatric facilities in western Lapland consist of the

fifty-five-bed Keropudas Hospital, which is located on the outskirts

of Tornio, and five mental-health outpatient clinics. There are around

one hundred mental-health professionals in the district (psychia¬

trists, psychologists, nurses, and social workers), and most have

completed a nine-hundred-hour, three-year course in family ther¬

apy. Many of the staff—including psychiatrist Birgitta Alakare and

psychologists Tapio Salo and Kauko Haarakangas —have been there

for decades, and today open-dialogue therapy is a well-polished

form of care.

Their conception of psychosis is quite distinct in kind, as it

doesn't really fit into either the biological or psychological category.

Instead, they believe that psychosis arises from severely frayed so¬

cial relationships. "Psychosis does not live in the head. It lives in the

in-between of family members, and the in-between of people," Salo

explained. "It is in the relationship, and the one who is psychotic

makes the bad condition visible. He or she 'wears the symptoms'

and has the burden to carry them."“

With most of the staff in the district trained in family therapy, the

system is able to respond quickly to a psychotic crisis. Whoever is

first contacted—by a parent, a patient seeking help, or perhaps a

school administrator —is responsible for organizing a meeting

within twenty-four hours, with the family and patient deciding

342

ANATOMY OF AN EPIDEMIC

where the meeting should be held. The patient’s home is the

preferred place. There must be at least two staff members present at

the meeting, and preferably three, and this becomes a "team” that

ideally will stay together during the patient's treatment. Everyone

goes to that first meeting aware that they "know nothing," said

nurse Mia Kurtti. Their job is to promote an "open dialogue” in

which everybody's thoughts can become known, with the family

members (and friends) viewed as coworkers. "We are specialists in

saying that we are not specialists," Birgitta Alakare said.

The therapists consider themselves guests in the patient's home,

and if an agitated patient runs off to his or her room, they simply

ask the patient to leave the door open, so that he or she can listen to

the conversation. "They hear voices, we meet them, and we try to

reassure them," Salo said. "They are psychotic, but they are not

violent at all." Indeed, most patients want to tell their story, and

when they speak of hallucinations and paranoid thoughts, the ther¬

apists simply listen and reflect upon what they've heard. "I think

[psychotic symptoms] are very interesting,” Kurtti said. "What's

the difference between voices and thoughts? We are having a con¬

versation."

No mention is made of antipsychotics in the first few meetings. If

the patient begins sleeping better and bathing regularly, and in other

ways begins to reestablish societal connections, the therapists know

that the patient's "grip on life" is strengthening, and that medica¬

tion will not be needed. Now and then, Alakare may prescribe a

benzodiazepine to help a person sleep or to dampen the patient's

anxiety, and eventually she may prescribe a neuroleptic at a low

dose. "Usually I suggest that the patient use it for some months,”

Alakare said. "But when the problems go away, after six months or

a year, or maybe even after three years, we try to stop the medica¬

tion."

From the outset, the therapists strive to give both the patient and

family a sense of hope. "The message that we give is that we can

manage this crisis. We have experience that people can get better,

and we have trust in this kind of possibility,” Alakare said. They

have found that it can take a long time —two, three, or even five

years —for a patient to recover. Although a patient's psychotic

BLUEPRINTS FOR REFORM

343

symptoms may abate fairly quickly, they are focused on the patient's

"grip on life" and repairing his or her relationship to society, and

that is a much bigger task. The team continues to meet with the pa¬

tient and family, and as this process unfolds, teachers and prospec¬

tive employers are asked to attend too. "It's about restoring social

connections," Salo said. "The 'in-between' starts working again,

with family and with friends.”

Over the past seventeen years, open-dialogue therapy has trans¬

formed "the picture of the psychotic population" in western Lap-

land. Since the 1992-93 study, not a single first-episode psychotic

patient has ended up chronically hospitalized. Spending on psychi¬

atric services in the region dropped 33 percent from the 1980s to

the 1990s, and today the district's per-capita spending on mental-

health services is the lowest among all health districts in Finland.

Recovery rates have stayed high: From 2002 to 2006, Tornio par¬

ticipated in a multinational study by Nordic countries of first-

episode psychosis, and at the end of two years, 84 percent of the

patients had returned to work or school, and only 20 percent were

taking antipsychotics. Most remarkable of all, schizophrenia is now

disappearing from the region. Families in western Lapland have be¬

come so comfortable with this gentle form of care that they call the

hospital (or one of the outpatient clinics) at the first sign of psy¬

chosis in a loved one, with the result being that today first-episode

patients typically have had psychotic symptoms for less than a

month and, with treatment initiated at this early stage, very few go

on to develop schizophrenia (the diagnosis is made after a patient

has been psychotic for longer than six months). Only two or three

new cases of schizophrenia appear each year in western Lapland, a

90 percent drop since the early 1980s.”

Tornio's success has drawn the attention of mental-health-care

providers in other European countries, and during the past twenty

years, two or three other groups in Europe have reported that the

combination of psychosocial care and limited use of neuroleptics

has produced good outcomes. 16 "This really happened," Seikkula

said. "It's not just a theory."

344

ANATOMY OF AN EPIDEMIC

On my way back to Helsinki, I kept puzzling over this one thought:

Why are the group meetings in Tornio so therapeutic? Given the

outcomes literature for neuroleptics, I could understand why selec¬

tive use of the drugs had proven to be so helpful. But why did open-

dialogue therapy help psychotic patients heal?

During my two days in Tornio, I sat in on three group sessions,

and although I don't speak Finnish, it was nevertheless possible to

gain a sense of the meetings' emotional tenor and to observe how

the conversation flowed. Everyone sat in a circle, in a very relaxed

and calm manner, and before anyone spoke, there often was a split-

second moment of silence, as if whoever was going to speak next

was gathering his or her thoughts. Now and then someone laughed,

and I couldn't identify a time when anyone was interrupted, and yet

no individual seemed to go on speaking too long, either. The con¬

versation seemed graced by gentility and humility, and both family

members and patients listened with rapt attention whenever the

therapists turned and spoke to each other. "We like to know what

they really think, rather than just have them give us advice," said

the parents in one of the meetings.

But that was the sum of it. It was all a bit mystifying, and even

the staff at Keropudas Hospital hadn't really been able to explain

why these conversations were so therapeutic. "The severe symp¬

toms begin to pass,” Salo said with a shrug. "We don't know how it

happens, but [open-dialogue therapy] must be doing something,

because it works.”

A Natural Antidepressant

In the early 1800s, Americans regularly turned to a book written by

Scottish physician William Buchan for medical advice. In Domestic

Medicine, Buchan prescribed this pithy remedy for melancholy:

The patient ought to take as much exercise in the open air as

he can bear ... A plan of this kind, with a strict attention to

BLUEPRINTS FOR REFORM

345

diet, is a much more rational method of cure, than confining

the patient within doors, and plying him with medicines. 17

Two centuries later, British medical authorities rediscovered the

wisdom of Buchan's advice. In 2004, the National Institute for

Health and Clinical Excellence, which acts as an advisory panel to

the country's National Health Service, decided that "antidepres¬

sants are not recommended for the initial treament of mild depres¬

sion, because the risk-benefit ratio is poor." Instead, physicians

should try non-drug alternatives and advise "patients of all ages

with mild depression of the benefits of following a structured and

supervised exercise programme." 18

Today, general practitioners in the UK may write a prescription

for exercise. "The evidence base for exercise as a treatment for de¬

pression is quite good," said Andrew McCulloch, executive director

of the Mental Health Foundation, a London-based charity that has

been promoting this alternative. "It also reduces anxiety. It's good

for self-esteem, control of obesity, et cetera. It has a broad-spectrum

effect." 19

In terms of its short-term efficacy as an antidepressant, studies

have shown that exercise produces a "substantial improvement"

within six weeks, that its effect size is "large," and that 70 percent

of all depressed patients respond to an exercise program. "These

success rates are quite remarkable," German investigators wrote in

2008. = “ In addition, over time, exercise produces a multitude of

"side benefits.” It enhances cardiovascular function, increases mus¬

cle strength, lowers blood pressure, and improves cognitive func¬

tion. People sleep better, they function better sexually, and they also

tend to become more socially engaged.

A 2000 study by James Blumenthal at Duke University also

revealed that it is unwise to combine exercise with drug therapy.

He randomized 156 older depressed patients into three groups —

exercise, Zoloft, and Zoloft plus exercise —and at the end of sixteen

weeks, those treated with exercise alone were doing as well as those

in the other two groups. 21 Blumenthal then tracked the patients for

another six months, with the patients free to choose whatever

346

ANATOMY OF AN EPIDEMIC

The Long-Term Benefit of Exercise for Depression

Treatment During

First Four Months

Percentage of Patients

in Remission at End of

Four Months

Percentage of Remitted

Patients Who Relapsed

in Six-Month Follow-up

Percentage of

Patients Depressed

at End of Ten

Months

Zoloft alone

6 9%

3 8%

5 2 %

Zoloft plus

6 6 %

3 1 %

5 5 %

exercise therapy

Exercise therapy

6 0%

3 0%

alone

In this study by Duke researchers, older patients with depression were treated for 16 weeks in

one ofthree ways, and then followed for another six months. Patients treated with exercise alone

had the lowest rates of relapse during the foMowing six months, and as a group, they were much

less likely to be suffering from depressive symptoms at the end often months. Source: Babyak,

M. "Exercise treatment for major depression." Psychosomatic Medicine 62 (2000): 6S S -3 8.1 00- 1 1 .

treatment they wanted during this period, and at the end the pa¬

tients treated initially with exercise alone were doing the best. Only

8 percent of those who had been well at the end of sixteen weeks

had relapsed during the follow-up, and by the end of ten months 70

percent of the exercise-only group were asymptomatic. In the two

Zoloft-exposed groups, more than 30 percent of the patients who

had been well at the end of sixteen weeks relapsed, and fewer than

50 percent were asymptomatic by the study's end. The "Zoloft plus

exercise" group had fared no better than the "Zoloft alone” pa¬

tients, which suggested that exposure to Zoloft negated the benefits

of exercise. "This was an unexpected finding, because it was as¬

sumed that combining exercise with medication would have, if

anything, an additive effect,” Blumenthal wrote. 22

In 2003, when Britain's Mental Health Foundation launched its

exercise-for-depression campaign, it took advantage of the fact that

general practitioners in Britain were already "prescribing” exercise

to patients with diabetes, hypertension, osteoporosis, and other

physical conditions. The delivery of this medical care requires

physicians to collaborate with local YMCAs, gyms, and recre¬

ational facilities, with these collaborations known as "exercise-

referral schemes," and thus the foundation simply needed to get the

GPs to start prescribing exercise to their depressed patients too.

BLUEPRINTS FOR REFORM

347

Today, more than 20 percent of the GPs in the UK prescribe exercise

to depressed patients with some frequency, which is four times the

percentage who did in 2004.

A "prescription" for exercise typically provides the patient with

twenty-four weeks of treatment. An exercise professional assesses

the patient's fitness and develops an appropriate "activity plan,"

with the patient then given discounted or free access to the collabo¬

rating YMCA or gym. Patients work out on exercise machines,

swim, and take various exercise classes. In addition, many exercise-

referral schemes provide access to "green gyms.” The outdoor pro¬

grams may involve group walks, outdoor stretching classes, and

volunteer environmental work (managing local woodlands, improv¬

ing footpaths, creating community gardens, etc.). Throughout the

six months of treatment, the exercise professional monitors the

patient’s health and progress.

As might be expected, patients have found ”exercise-on-

prescription" treatment to be quite helpful. They told the Mental

Health Foundation that exercise allowed them to "take control of

their recovery" and to stop thinking of themselves as "victims" of a

disease. Their confidence and self-esteem increased; they felt calmer

and more energetic. Treatment was now focused on their "health,"

rather than on their "illness."

"The fathers of medicine wouldn't be surprised about what we

are doing," McCulloch said. "They would say, 'Hasn't science gone

any further? Diet and exercise? This is what is new?' If they could

travel in a time machine, they would think we were mad, because

people have been saying these things for thousands of years."

These Kids Are Awesome

The children who end up living at Seneca Center in San Leandro,

California, have come to the last stop for severely disturbed youth

in the northern part of the state. The children, five to thirteen years

old, have usually cycled through several foster homes and have had

multiple hospitalizations, and their behavior has been so difficult

348

ANATOMY OF AN EPIDEMIC

that there are no foster homes or hospitals left that want to see them

again. In bureaucratic terms, they are "level-14" kids, which is the

designation given to the most troubled kids in California, but since

these children have flunked out of other level-14 facilities, they are

better described as ”level-14-plus-plus” youth. Counties pay Seneca

Center $15,000 a month to shelter a child and, not surprisingly,

when the children arrive at the center, most are on heavy-duty drug

cocktails. "They are so drugged up that they are asleep most of the

day," said Kim Wayne, director of the residence program. 23

And then their lives begin to change dramatically.

I visited one of Seneca Center's two residences for younger chil¬

dren in the summer of 2009, and when I entered, here is what I saw:

a young African American girl wearing headphones singing along to

a Jordin Sparks song; a second slightly older African American girl

sitting at the kitchen table, leafing through photos of their recent

group trip to Disneyland; and two African American boys at the

table goofing around with each other and racing to see who could

drink a glass of water the fastest. A Caucasian girl sat on the couch,

and the sixth resident of the house, I later learned, was off at a

swimming lesson. Within a short while, the girl with the head¬

phones was singing a cappella (and quite well), and the girl huddled

over the photo album had started calling me Bob Marley, appar¬

ently because I knew who Jordin Sparks was. Now and then, one of

the children erupted into laughter.

"The kids are so grateful to be off the drugs," said therapist Kari

Sundstrom. "Their personalities come back. They are people again."

The two Seneca Center homes may be the last residential facilities

in the United States where severely troubled children under county

or state control are treated without psychiatric drugs. Indeed, in

most child-psychiatry circles, this would be considered unethical.

'T've been told, 'If your child had a disease, would you deny your

child medication that helped him get better?' " said Seneca Center

founder and CEO Ken Berrick. And even within the agency, which

has a staff of around seven hundred and provides a variety of ser¬

vices to two thousand troubled children and youth in northern

California, the residence program is an anomaly.

When the center opened in 1985, Berrick and others sought to

BLUEPRINTS FOR REFORM

349

hire consulting psychiatrists who would use psychiatric medications

in a "conservative” fashion and never for purposes of "behavioral

control.” Some used the drugs more than others, and then there was

Tony Stanton, whom the agency hired in 1987 to oversee the chil¬

dren's residential program. In the 1960s, he had trained at Langley

Porter Hospital in San Francisco, which at the time emphasized the

"importance of environment" to a child's mental health. Stanton's

own "attachment theory" convinced him of the importance of emo¬

tional relationships to a child's well-being. Then, in the late 1970s,

while he was in charge of a psychiatric ward for children at a

county hospital, he assigned a "mentor” to every child. The chil¬

dren weren't medicated, and he saw a number of them become at¬

tached to their mentors and "blossom.”

"That experience allowed me to see this therapeutic principle in

action," Stanton said. "You just can't organize yourself without a

connection to another human being, and you can't make that con¬

nection if you embalm yourself with drugs.”

When a child enters Seneca Center's residential program, Stanton

does not ask "what's wrong” with the child, but rather "what hap¬

pened to them.” He gets the department of social services, schools,

and other agencies to send him all of the records they have on the

child, and then he spends eight to ten hours constructing a "life

chart.” As might be expected, the charts regularly tell of children

who have been sexually abused, physically abused, and horribly

neglected. But Stanton also tracks their medication history and how

their behavior may have changed after they were put on a particular

drug, and given that the children who arrive at Seneca Center are se¬

riously disturbed, these medical histories regularly tell of psychiatric

care that has worsened their behavior. "I'll have people say, 'We

want to try the child on Risperdal now,’ and I'll say, 'Let’s take a

look at the chart and see what happened before. I don't think it will

be helpful,' " Stanton said.

The children regularly arrive at the center on drug cocktails, and

thus it can take a month or two to withdraw the medications. Often

the children, having been repeatedly told that they need the drugs,

are nervous about this process —"One kid told me 'What do you

mean you are taking me off my meds? I'll destroy your program,' "

350

ANATOMY OF AN EPIDEMIC

Stanton said—and often they do become more aggressive for a time.

Staff may have to use "physical restraints" more frequently (they

have been trained to hold the kids in "safe” ways). However, these

behavioral problems usually begin to abate and by the end of the

withdrawal process, the child has "come alive.”

"It's wonderful," Kim Wayne said. "Most times when the kids

come in, they can't keep their heads up, they are lethargic, they are

just a blank and there is minimal engagement. You just can't get

through to them. But when they come off their meds, you can en¬

gage them and you get to see who they are. You get a sense of their

personality, their sense of humor, and what kinds of things they like

to do. You may have to use physical restraints for a time, but to me,

it's worth it."

Once they are off meds, the children begin to think of themselves

in a new way. They see that they can control their own behavior,

and this gives them a sense of "agency," Stanton said. The Seneca

Center uses behavior-modification techniques to promote this self-

control, with the children constantly having to abide by a well-

defined set of rules. They have to ask permission to go to the

bathroom and enter bedrooms, and if they don't comply with

the rules, they may be sent to a "time-out" or lose a privilege. But

the staff tries to focus on reinforcing positive behaviors, offering

words of praise and rewarding the kids in various ways. The chil¬

dren are required to keep their rooms clean and perform a daily

chore, and at times they will help prepare the evening meal.

"The question of feeling in charge of yourself and being responsi¬

ble for yourself is the central issue in their lives," Stanton said.

"They may only partially get there while they are with us, but when

we are really successful, we see them develop this sense of 'Oh, I can

do this; I want to be in control of myself and my own life.' They see

themselves as having that power.”

Even more important, once the children are off the medications

they are better able to form emotional bonds with the staff, and the

staff with them. They have known rejection all their lives, and they

need to form relationships that nurture a belief that they are worthy

of being loved, and when that happens, their "internal narrative”

can switch from "I'm a bad kid” to "I'm a good kid.”

BLUEPRINTS FOR REFORM

351

"They come in thinking, T'm crazy, you are going to hate me,

you are going to get rid of me, I'm going to be the worst kid you

have ever seen,” said therapist Julie Kim. "But then they become

willing to form [emotional] attachments, and that’s such an amaz¬

ing thing. You can see the power of a relationship to change a kid,

and even the kids who seem the toughest when they come in here,

who don't make any progress at first, eventually do."

Although Kim and others can tell anecdotal stories of children

discharged from the residence program who have returned to ordi¬

nary schools and done well, the center has not done a long-term

follow-up of the children that have gone through their residence

program. The only statistical information the center has to show

that its residence program works is this: 225 children lived at its res¬

idences from 1995 to 2006, and nearly all were discharged to lower-

level group homes or to a foster home or to their biological families.

Their time at Seneca Center at least turned their lives in a new di¬

rection. And yet, it is difficult to be optimistic that their lives con¬

tinue down that path. Their emotional and behavioral problems do

not completely go away, and so many of the discharged children —

and perhaps most —are remedicated. They return to a world where

that is the norm. Their time at Seneca Center may primarily provide

them with a temporary oasis from a society prone to asking "what's

wrong with them," and thus, if we want to assess whether the no¬

medication policy of the center's residence program is providing the

children with a "benefit," instead of looking to the future, perhaps

we should focus on the present and look at what it is like for the

children to have this opportunity to "come alive” for a time and

fully feel the world.

I spent two days at the center, and there were three children in

particular I had a chance to interact with. One was a twelve-year-

old boy I'll call Steve. When he'd arrived at Seneca Center a year

earlier, he'd been so filled with suicidal and self-destructive habits

that doctors thought he had suffered brain damage from all of his

head-banging episodes. Since then he’d become very attached to

Stacy, one of the male staff at his house, and during our interview,

he flopped down into a chair, grinned, and immediately took over

the conversation. "I hate taking medicine. It is real boring being on

352

ANATOMY OF AN EPIDEMIC

drugs,” he said, and then he began telling us about migratory tur¬

tles, a raccoon that had been poking around their house, a trip to

McDonald’s with Stacy, and what people needed to do to prepare

for an earthquake. All of that was prelude to a story about a comic

book he wanted to write, titled The Adventures of Sam Dune and

Rock, which featured numerous "good and evil" characters, includ¬

ing one who needed to take drugs to keep from going mad. Steve

held center stage for at least an hour, and afterward he happily in¬

formed Stacy that the interview had been "cold, real cold,” which

of course meant that he had enjoyed himself immensely.

I'll call the two African American girls I met in the Los Reyes

house Layla (the a cappella singer) and Takeesha. Their "life charts"

both told of nightmarish pasts, and that was particularly true

for Takeesha. When she'd arrived at the Seneca Center in 2006, at

age seven, she was described as delusional, guarded, suspicious, un¬

cooperative, and very sedated. After we spent thirty minutes or so at

the kitchen table, talking about American Idol and the trip they had

taken to Disneyland, Takeesha asked if we could go outside and

play catch with a football. We did that for a while, and then Takee¬

sha got permission to ride her bike in the street, but only if she

promised to go only a few houses away in either direction, and sud¬

denly she came to a screeching halt in the driveway. "I'm going to

Burger King. What do you want?” she announced. Seconds later she

proudly returned holding an imaginary bag filled with a Whopper,

French fries, and a Coke, which I paid for with an equally imagi¬

nary five-dollar bill, asking if she would please make change. When

it came time to say good-bye, Layla asked for a hug, and then

Takeesha —having scurried into her bedroom to find something-

held out what appeared to be a package of gum, except for the fact

that the piece sticking out was clearly metallic in kind.

"It’s just gum!" she squealed when I felt the slight buzz.

The next day I sat in on their class. I spoke briefly with the teacher

and several of the aides, and they all said the same thing. "These kids

are awesome! We could drug the kids into submission, but for what

purpose? I love this place!” I was there with Tony Stanton, and after

a while it became evident that our presence was causing a dilemma

for both Layla and Takeesha. They were supposed to be paying at-

BLUEPRINTS FOR REFORM

353

tention to the teacher, and they knew that if they didn't, they would

be sent to time-out (there was a steady march of children to the time¬

out corner), and yet both were clearly intent on making contact with

us. We were sitting by the sink, and at last both girls decided they

just had to wash their hands. As Layla went back to her seat, she

couldn't resist giving us a high-five, even though this was a breach of

class protocol. Meanwhile, as Takeesha passed by my chair, she

whispered, "Bob Marley, what are you doing here?”

At that moment, I couldn't imagine any outcome data of a more

powerful sort.

On the Drawing Board

Psychiatry and the rest of medicine regularly proclaim that treat¬

ments should be "evidence-based." The solutions we've reviewed in

this chapter all meet that standard. David Healy's belief that the

psychiatric medications should be used in a cautious manner, the

open-dialogue program in Tornio, and the prescribing of exercise as

a first-line therapy for mild-to-moderate depression are all rooted in

good science. The same can be said of Tony Stanton's medication-

withdrawal policy. Earlier in the book, we saw that children put on

stimulants, antidepressants, and antipsychotics often worsen over

the long term, and that those who end up on drug cocktails can be

said to be suffering from an iatrogenic illness. The medications can

be viewed as pathological agents, and thus when Tony Stanton

takes the Seneca Center children off the drugs, he is —in essence-

providing treatment for a "disease.” The proof that the treatment

works can be found in the staff's observation that the children

"come alive.”

Given this perspective, it would be helpful if we could identify a

mainstream medication-withdrawal program in adults, one that

arises from research into this process. How quickly should the

drugs be withdrawn? After the drugs are withdrawn, how long does

it take for the brain to "renormalize?" Or does it? Do neuronal

feedback mechanisms reset? Do presynaptic neurons begin releasing

354

ANATOMY OF AN EPIDEMIC

normal amounts of the neurotransmitter? Do receptor densities re¬

turn to normal? Psychiatry has been using psychotropic medications

for more than fifty years, yet all of these questions basically remain

unanswered. Indeed, people who want to stop taking the drugs have

been mostly left to fend for themselves, sharing information on the

Internet and through their various peer networks.

However, in the fall of 2 009, a major provider of mental-health

services in eastern and central Massachusetts, Advocates, drew up a

plan for a medication-withdrawal study. Advocates provides ser¬

vices to several thousand people with psychiatric difficulties, and in

2008, when it asked its clients for "new ideas,” many put this at the

top of their wish list, said Keith Scott, director of recovery and peer

support services. "A number said, 'Geez, it would be great if there

would be a place where I could try to stop taking my medication

without being threatened with losing my housing or my services and

the relationships that are important to me.' That seemed extremely

reasonable to me." 24

The medical director of Advocates, Chris Gordon, who is an as¬

sistant clinical professor of psychiatry at Harvard Medical School,

said that he hoped to obtain funding from either the state Depart¬

ment of Mental Health or a federal agency. Advocates plans to

provide both medical and social support to patients in the "drug

reduction/elimination" study, and Gordon said that if patients begin

to struggle during the withdrawal process, he'd like to see if they

can be helped through that crisis without restarting the medica¬

tions. He'd like to follow the patients in the program for five years,

so Advocates can get a sense of their long-term outcomes.

This initiative, Gordon said, is being driven in part by the fact

that the mentally ill are now dying twenty-five years earlier than

their peers, and that it is clear that the atypical antipsychotics,

which regularly cause metabolic dysfunction, are contributing to

that early death problem. “We see it all the time. We could name a

terrible list of people we know personally and care about who died

way too young," he said. 25

BLUEPRINTS FOR REFORM

355

The Alaska Project

If I had to identify one person in the United States who was doing

the most to "change the system," I would pick Alaska attorney Jim

Gottstein. A 1978 graduate of Harvard Law School, Gottstein was

hospitalized twice in the 1980s because of bouts of mania, and that

personal experience has inspired a lifelong career of fighting to im¬

prove the plight of the mentally ill in our society.

During the 1980s and 1990s, Gottstein joined other attorneys in

an epic lawsuit by the Alaska Mental Health Association against the

state. In 1956, Congress allowed Alaska's territorial administrators

to set aside one million acres of prime federal land as an asset that

would fund mental-health programs, but in 1978 the state legisla¬

ture redesignated the acreage as "general grant lands," leaving the

mentally ill out in the cold. The state basically "stole” the land,

Gottstein said, and eventually he and other attorneys negotiated a

$1.1 billion settlement. 26 The state gave $200 million and nearly a

million acres of land to a newly created Mental Health Trust Au¬

thority, with the trust allowed to spend this money as it sees fit,

without the legislature's approval.

In 2002, Gottstein founded a non-profit organization, Psych-

Rights, and the first thing that it did was mount a "public informa¬

tion" campaign. PsychRights brought various people to Anchorage

to speak to judges, lawyers, psychiatrists, and the general public

about the outcomes literature for antipsychotics.* Gottstein be¬

lieved that this would provide a foundation for a lawsuit challenging

the state's right to medicate patients forcibly, and for lobbying the

Mental Health Trust Authority to fund a Soteria-like home, where

psychotic patients who didn't want to take neuroleptics could get

help.

"The public opinion is that the meds work, and that if people

weren't crazy, they would know that the drugs are good for them,"

Gottstein said. "But if we can get judges and lawyers to understand

* In the interest of full disclosure, I was one of the speakers at several of those

events.

356

ANATOMY OF AN EPIDEMIC

that it's not necessarily good for the person and potentially very

harmful, they would tend to honor a person's legal right to refuse

treatment. In the same vein, if the public knew that there are other

non-drug approaches like Soteria that work better, they would sup¬

port alternatives, right?"

State case laws governing the forced treatment of psychiatric pa¬

tients date back to the late 1970s. Although state supreme courts

typically ruled that patients have a right to refuse treatment (in non¬

emergency situations), they nevertheless noted that antipsychotics

were understood to be "a medically sound treatment of mental dis¬

ease," and thus hospitals could apply to a court to sanction forced

treatment. At such hearings, hospitals regularly argue that no com¬

petent person would refuse "medically sound treatment," and thus

courts consistently order patients to be medicated. 27 But in 2003,

Gottstein initiated a forced-drugging lawsuit on behalf of a woman

named Faith Myers, and he put the medication on trial, arguing that

the state could not show that it was in her best medical interest to

take an antipsychotic. He got Loren Mosher and a second psychia¬

trist who knows the outcomes literature well, Grace Jackson, to

serve as his expert witnesses, and he also filed copies of the many re¬

search studies that tell of how neuroleptics can worsen long-term

outcomes.

Having become versed in the scientific literature, the Alaska

Supreme Court gave PsychRights a stunning legal victory in 2006.

"Psychotropic medication can have profound and lasting negative

effects on a patient's mind and body," the court wrote. These drugs

"are known to cause a number of potentially devastating side ef¬

fects.” As such, it ruled in Myers v. Alaska Psychiatric Institute that

a psychiatric patient could be forcibly medicated only if a court "ex¬

pressly finds by clear and convincing evidence that the proposed

treatment is in the patient’s best interest and that no less intrusive

alternative is available." 28 In Alaska case law, antipsychotics are no

longer viewed as treatment that will necessarily help psychotic

people.

In 2004, Gottstein launched an effort to get the Mental Health

Trust Authority to fund a Soteria home in Anchorage, which would

offer psychotic patients the type of care that Loren Mosher's Soteria

BLUEPRINTS FOR REFORM

357

Project did in the 1970s. Once again, he relied on the persuasive

powers of the scientific literature to carry his argument, and in the

summer of 2009, a seven-bedroom Soteria home opened a few miles

south of downtown. The director of the project, Susan Musante,

formerly led a psychiatric rehabilitation program at the University

of New Mexico Mental Health Center; the consulting psychiatrist,

Aron Wolf, is a well-respected figure in Alaskan psychiatry.

"We want to work with younger people who have been on psy¬

chiatric medications for only a short time, and by getting them off

the meds and helping them get better, we hope to keep them from

going down the path of chronic illness," Musante said. "Our expec¬

tation is that people will recover. We expect them to go to work or

to school, to return to age-appropriate behavior. We are here to help

them to dream again and to pursue those dreams. We are not set up

to funnel them onto SSI or SSDI." 29

Gottstein now has his sights set on a legal challenge national in

scope. He has been filing lawsuits that challenge the medicating of

foster children and poor children in Alaska (the poor are covered by

Medicaid), and ultimately he hopes to take one of these cases to the

U.S. Supreme Court. He sees this as a 14th Amendment issue, with

the children being deprived of their liberty without due process of

law. At the heart of any such case would be a scientific question: Are

the foster children being treated with medications that help, or are

they being treated with tranquilizing drugs that cause long-term

harm?

"I analogize it to Broum v. Board of Education," Gottstein said.

"Before that decision, there was widespread acceptance in the

United States that segregation is OK. The Supreme Court had previ¬

ously said that segregation was OK. But then in Brown v. Board of

Education, the court said it wasn't OK, and that really changed

public opinion. Today you can't get anyone to say segregation is

OK. And that’s how I visualize this whole effort."

ANATOMY OF AN EPIDEMIC

358

We the People

As a society, we put our trust in the medical profession to develop

the best possible clinical care for diseases and ailments of all types.

We expect that the profession will be honest with us as it goes about

this task. And yet, as we look for ways to stem the epidemic of dis¬

abling mental illness that has erupted in this country, we cannot

trust psychiatry, as a profession, to fulfill that responsibility.

For the past twenty-five years, the psychiatric establishment has

told us a false story. It told us that schizophrenia, depression, and

bipolar illness are known to be brain diseases, even though —as the

MindFreedom hunger strike revealed—it can't direct us to any sci¬

entific studies that document this claim. It told us that psychiatric

medications fix chemical imbalances in the brain, even though

decades of research failed to find this to be so. It told us that Prozac

and the other second-generation psychotropics were much better

and safer than the first-generation drugs, even though the clinical

studies had shown no such thing. Most important of all, the psychi¬

atric establishment failed to tell us that the drugs worsen long-term

outcomes.

If psychiatry had been honest with us, the epidemic could have

been curbed long ago. The long-term outcomes would have been

publicized and discussed, and that would have set off societal

alarms. Instead, psychiatry told stories that protected the image of

its drugs, and that storytelling has led to harm done on a grand and

terrible scale. Four million American adults under sixty-five years

old are on SSI or SSDI today because they are disabled by mental ill¬

ness. One in every fifteen young adults (eighteen to twenty-six years

old) is "functionally impaired” by mental illness. Some 250 children

and adolescents are added to the SSI rolls daily because of mental

illness. The numbers are staggering, and still the epidemic-making

machinery rolls on, with two-year-olds in our country now being

"treated" for bipolar illness.

As I noted earlier in this chapter, I believe the MindFreedom Six

showed what must be done if we are going to halt this epidemic. We

need to become informed about the long-term outcomes literature

BLUEPRINTS FOR REFORM

359

reviewed in this book, and then we need to ask the NIMH, NAMI,

the APA, and all those who prescribe the medications to address the

many questions raised by that literature. In other words, we need to

have an honest scientific discussion. We need to talk about what is

truly known about the biology of mental disorders, about what the

drugs actually do, and about how the drugs increase the risk that

people will become chronically ill. If we could have that discussion,

then change surely would follow. Our society would embrace and

promote alternative forms of non-drug care. Physicians would pre¬

scribe the medications in a much more limited, cautious manner. We

would stop putting foster children on heavy-duty cocktails and pre¬

tending that it was medical care. In short, our societal delusion

about a "psychopharmacology" revolution could at last fade away,

and good science could illuminate the path to a much better future.

Epilogue

"Few dare to announce unwelcome truth.

- EDWIN PERCY WHIPPLE (1 866)'

This book tells a history of science that leads readers to a socially

awkward place. Our society believes that psychiatric medications

have led to a "revolutionary” advance in the treatment of mental

disorders, and yet these pages tell of a drug-induced epidemic of dis¬

abling mental illness. Society sees the beautiful woman, and this

book directs the reader's gaze to the old woman. It's never easy to

hold a belief that is out of sync with what the rest of society be¬

lieves, and in this instance, it's particularly difficult because the

story of progress is told by figures of scientific authority —the APA,

the NIMH, and psychiatrists at prestigious universities such as Har¬

vard Medical School. Disagree with the common wisdom on this

topic, and it seems that you must be a card-carrying member of the

flat-Earth society.

But for those readers still wondering about the history told here,

I offer one last story. You can read it and decide for yourself

whether you are now, metaphorically speaking, in the flat-Earth

camp.

After I interviewed Jaakko Seikkula at the University of

Jyvaskyla, he asked me to give a short talk on the history of an-

tipsychotics to a few of his colleagues. Now, Seikkula and others at

Keropudas Hospital in Tornio did not decide to use antipsychotics

362

ANATOMY OF AN EPIDEMIC

in a selective manner because they thought that the drugs worsened

psychotic symptoms over the long term. Instead, they observed that

many people did better when off them. Thus, when I spoke to

Seikkula's colleagues at the University of Jyvaskyla, this notion that

antipsychotics can make people chronically ill was something they

hadn't thought much about before, and at the end of my talk, one of

the members of our circle asked if this could be true of antidepress¬

ants, too. He and others had been researching the long-term out¬

comes of depressed patients in Finland, and charting too whether

they had used the drugs, and they had been startled by their results.

So, dear readers, ask yourself this: What do you think they

found? And are you surprised?

NOTES

To read many of the source documents listed here, go to madinamerica.com or

robertwhitaker.org

Chapter 1: A Modern Plague

1. J. Bronowski, The Ascent of Man (New York: Little, Brown & Co., 1973), 153.

2. IMS Health, "2007 top therapeutic classes by U.S. sales."

3. U.S. Department of Health and Human Services, Mental Health: A Report of the

Surgeon General (1999), 3, 68, 78.

4. E. Shorter, A History of Psychiatry (New York: John Wiley & Sons, 1997), 255.

5. R. Friedman, "On the Horizon, Personalized Depression Drugs," New York Times ,

June 19, 2007.

6. Boston Globe editorial, "When Kids Need Meds," June 22, 2007.

7. Address by Carolyn Robinowitz, APA Annual Conference, Washington, D.C., May

4, 2008.

8. C. Silverman, The Epidemiology of Depression (Baltimore: Johns Hopkins Press,

1968), 139.

9. Social Security Administration, annual statistical reports on the SSDI and SSI pro¬

grams, 1987-2008. To calculate a total disability number for 1987 and 2007, I

added the number of recipients under age sixty-five receiving an SSI payment that

year and the number receiving an SSDI payment due to mental illness, and then I ad¬

justed the total to reflect the fact that one in every six SSDI recipients also receives

an SSI payment. Thus, mathematically speaking: SSI recipients + (.833 x SSDI recip¬

ients) = total number of disabled mentally ill.

10. Silverman, The Epidemiology of Depression, 139.

11. The annual Social Security Administration reports don't provide data on the specific

364

NOTES

diagnoses of SSI and SSDI recipients disabled by mental illness. However, various re¬

searchers have reported that affective disorders now make up 37 percent (or more)

of the disabled mentally ill. See, for instance, J. Cook, "Results of a multi-site clini¬

cal trials study of employment models for mental health consumers," available at:

psvch.uic.edu/EIDP/eidp-3-20-03.pdf .

12. U.S. Government Accountability Office, "Young adults with serious mental illness"

(June 2008).

13. Social Security Administration, annual statistical reports on the SSI program, 1996-

2008; and Social Security Bulletin, Annual Statistical Supplement, 1988-1992.

Chapter 2: Anecdotal Thoughts

1. Adlai Stevenson, speech at University of Wisconsin, October 8, 1952. As cited by L.

Frank, Quotationary (New York: Random House, 2001), 430.

Chapter 3: The Roots of an Epidemic

1. J. Young, The Medical Messiahs (Princeton, NJ: Princeton University Press, 1967),

281.

2. Chemical Heritage Foundation, "Paul Ehrlich, Pharmaceutical Achiever," accessed

at chemheritage.org .

3. P. de Kruif, Dr. Ehrlich's Magic Bullet (New York: Pocket Books, 1940), 387.

4. L. Sutherland, Magic Bullets (Boston: Little, Brown and Company, 1956), 127.

5. L. Garrett, The Coming Plague (New York: Penguin, 1995), 49.

6. T. Mahoney, The Merchants of Life (New York: Harper &c Brothers, 1959), 14.

7. "Mind Is Mapped in Cure of Insane," New York Times, May 15, 1937.

8. "Surgery Used on the Soul-Sick," New York Times, June 7, 1937.

9. A. Deutsch, The Shame of the States (New York: Harcourt Brace, 1948), 41.

10. E. Torrey, The Invisible Plague (New Brunswick, NJ: Rutgers University Press,

2001), 295.

11. G. Grob, The Mad Among Us (Cambridge, MA: Harvard University Press, 1994),

189.

12. "Need for Public Education on Psychiatry Is Stressed," New York Times, November

16, 1947.

Chapter 4: Psychiatry's Magic Bullets

1. E. Valenstein, Blaming the Brain (New York: The Free Press, 1998), 38.

2. J. Swazey, Chlorpromazine in Psychiatry (Cambridge, MA: MIT Press, 1974), 78.

3. Ibid, 79.

4. Ibid, 105.

5. Ibid, 134-35.

6. F. Ayd Jr., Discoveries in Biological Psychiatry (Philadelphia: Lippincott, 1970), 160.

7. Symposium proceedings, Chlorpromazine and Mental Health (Philadelphia: Lea

and Fabiger, 1955), 132.

8. Ayd, Discoveries in Biological Psychiatry, 121.

9. M. Smith, Small Comfort (New York: Praeger, 1985), 23.

NOTES

3 65

10. Ibid, 26.

11. Ibid, 72.

12. "TB and Hope," Time, March B, 1952.

13. Valenstein, Blaming the Brain, 38.

14. "TB Drug Is Tried in Mental Cases," New York Times, April 7, 1957.

15. M. Mintz, The Therapeutic Nightmare (Boston: Houghton Mifflin, 1965), 166.

16. Ibid, 488.

17. Ibid, 481.

18. Ibid, 59, 62.

19. T. Mahoney, The Merchants of Life (New York: Harper 8c Brothers, 1959), 4, 16.

20. Mintz, The Therapeutic Nightmare, 83.

21. Swazey, Chlorpromazine in Psychiatry, 190.

22. "Wonder Drug of 1954?" Time, June 14, 1954.

23. "Pills for the Mind," Time, March 7, 1955.

24. "Wonder Drugs: New Cures for Mental Ills?" U.S. News and World Report, June

17 , 1955 .

25. "Pills for the Mind," Time, March 7, 1955.

26. "Don't-Give-a-Damn Pills," Time, February 27, 1956.

27. Smith, Small Comfort, 67-69.

28. "To Nirvana with Miltown," Time, July 7, 1958.

29. "Wonder Drug of 1 954?" Time, June 14, 1954.

30. "TB Drug Is Tried in Mental Cases," New York Times, April 7, 1957.

31. Smith, Small Comfort, 70.

32. "Science Notes: Mental Drug Shows Promise," New York Times, April 7, 1957.

33. "Drugs and Depression," New York Times, September 6, 1959.

34. H. Himwich, "Psychopharmacologic drugs," Science 127 (1958): 59-72.

35. Smith, Small Comfort, 110.

36. Ibid, 104.

37. The NIMH Psychopharmacology Service Center Collaborative Study Group, "Phe-

nothiazine treatment in acute schizophrenia," Archives of General Psychiatry 10

( 1964 ): 246 - 61 .

38. Valenstein, Blaming the Brain, 70-79. Also see David Healy, The Creation of

Psychopharmacology (Cambridge, MA: Harvard University Press, 2002), 106, 205-

206 .

39. J. Schildkraut, "The catecholamine hypothesis of affective disorders," American

Journal of Psychiatry 111 (1965): 509-22.

40. Valenstein, Blaming the Brain, 82.

41. A. Baumeister, "Historical development of the dopamine hypothesis of schizophre¬

nia," Journal of the History of the Neurosciences 1 1 (2002): 265-77.

42. Swazey, Chlorpromazine in Psychiatry, 4.

43. Ibid, 8.

44. Ayd, Discoveries in Biological Psychiatry, 215-16.

45. Ibid, 127.

46. Ibid, 195.

366

NOTES

Chapter 5: The Hunt for Chemical Imbalances

1. T. H. Huxley, Critiques and Addresses (London: Macmillan &c Co., 1873), 229.

2. E. Azmitia, "Awakening the sleeping giant," Journal of Clinical Psychiatry 52

(1991), suppl. 12:4-16.

3. M. Bowers, "Cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid

in psychiatric patients," International Journal of Neuropharmacology 8 (1969):

255-62.

4. R. Papeschi, "Homovanillic and 5-hydroxyindoleacetic acid in cerebrospinal fluid of

depressed patients," Archives of General Psychiatry 25 (1971): 354-58.

5. M. Bowers, "Lumbar CSF 5-hydroxyindoleacetic acid and homovanillic acid in af¬

fective syndromes," Journal of Nervous and Mental Disease 158 (1974): 325-30.

6. D. L. Davies, "Reserpine in the treatment of anxious and depressed patients,"

Lancet 2 (1955): 117-20.

7. J. Mendels, "Brain biogenic amine depletion and mood," Archives of General Psy¬

chiatry 30 (1974): 447-51.

8. M. Asberg, "Serotonin depression: A biochemical subgroup within the affective dis¬

orders?" Science 191 (1976): 478-80; M. Asberg, "5-HIAA in the cerebrospinal

fluid," Archives of General Psychiatry 33 (1976): 1193-97.

9. H. Nagayama, "Postsynaptic action by four antidepressive drugs in an animal

model of depression," Pharmacology Biochemistry and Behavior 15 (1981): 125-

30. Also see H. Nagayama, "Action of chronically administered antidepressants on

the serotonergic postsynapse in a model of depression," Pharmacology Biochem¬

istry and Behavior 25 (1986): 805-11.

10. J. Maas, "Pretreatment neurotransmitter metabolite levels and response to tricyclic

antidepressant drugs," American Journal of Psychiatry 141 (1984): 1159-71.

11. J. Lacasse, "Serotonin and depression: a disconnect between the advertisements and

the scientific literature," PloS Medicine 2 (2005): 1211-16.

12. C. Ross, Pseudoscience in Biological Psychiatry (New York: John Wiley &c Sons,

1995), 111.

13. Lacasse, "Serotonin and depression."

14. D. Healy, "Ads for SSRI antidepressants are misleading," PloS Medicine news

release, November 2005.

15. I. Creese, "Dopamine receptor binding predicts clinical and pharmacological poten¬

cies of antischizophrenic drugs," Science 192 (1976): 481-83; P. Seeman, "Antipsy¬

chotic drug doses and neuroleptic/dopamine receptors," Nature 261 (1976J: 177-79.

16. "Schizophrenia: Vast effort focuses on four areas," New York Times, November 13,

1979.

17. M. Bowers, "Central dopamine turnover in schizophrenic syndromes," Archives of

General Psychiatry 31 (1974): 50-54.

18. R. Post, "Cerebrospinal fluid amine metabolites in acute schizophrenia," Archives

of General Psychiatry 32 (1975): 1063-68.

19. J. Haracz, "The dopamine hypothesis: an overview of studies with schizophrenic

patients," Schizophrenia Bulletin 8 (1982): 438-58.

NOTES

367

20. T. Lee, "Binding of 3 H-neuroleptics and 3 H-apomorphine in schizophrenic brains,"

Nature 374 (1978): 897-900.

21. D. Burt, "Antischizophrenic drugs: chronic treatment elevates dopamine receptor

binding in brain," Science 196 (1977): 326-27.

22. M. Porceddu, "[ 3 H]SCH 23390 binding sites increase after chronic blockade of d-1

dopamine receptors," European Journal of Pharmacology 118 (1985): 367-70.

23. A. MacKay, "Increased brain dopamine and dopamine receptors in schizophrenia,"

Archives of General Psychiatry 39 (1982): 991-97.

24. J. Kornhuber, " 3 H-spiperone binding sites in post-mortem brains from schizo¬

phrenic patients," Journal of Neural Transmission 75 (19 8 9): 1-10.

25. J. Martinot, "Striatal D 2 dopaminergic receptors assessed with positron emission

tomography and bromospiperone in untreated schizophrenic patients," Ameri¬

can Journal of Psychiatry 147 (1990): 44-50; L. Farde, "D 2 dopamine receptors in

neuroleptic-na'ive schizophrenic patients," Archives of General Psychiatry 47 (1990):

213-19; J. Hietala, "Striatal D 2 dopamine receptor characteristics in neuroleptic-

nai've schizophrenic patients studied with positron emission tomography," Archives

of General Psychiatry 51 (1994): 116-23.

26. P. Deniker, "The neuroleptics: a historical survey," Acta Psychiatrica Scandinavica

82, suppl. 358 (1990): 83-87. Also: "From chlorpromazine to tardive dyskinesia,"

Psychiatric Journal of the University of Ottawa 14 (1989): 253-59.

27. J. Kane, "Towards more effective antipsychotic treatment," British Journal of Psy¬

chiatry 165, suppl. 25 (1994): 22-31.

28. E. Nestler and S. Hyman, Molecular Neuropharmacology (New York: McGraw

Hill, 2002), 392.

29. J. Mendels, "Brain biogenic amine depletion and mood," Archives of General Psy¬

chiatry 30 (1974): 447-51.

30. P. Deniker, "The neuroleptics: a historical survey," Acta Psychiatrica Scandinavica

82, suppl. 358 (1990): 83-87. Also: "From chlorpromazine to tardive dyskinesia,"

Psychiatric Journal of the University of Ottawa 14 (1989): 253-59.

31. D. Healy, The Creation of Psychopharmacology (Cambridge, MA: Harvard Univer¬

sity Press, 2002), 217.

32. E. Valenstein, Blaming the Brain (New York: The Free Press, 1998), 96.

33. U.S. Department of Health and Human Services, Mental Health: A Report of the

Surgeon General (1999), 3, 68, 78.

34. J. Glenmullen, Prozac Backlash (New York: Simon & Schuster, 2000), 196.

35. Lacasse, "Serotonin and depression."

36. R. Fuller, "Effect of an uptake inhibitor on serotonin metabolism in rat brain," Life

Sciences 15 (1974): 1161-71.

37. D. Wong, "Subsensitivity of serotonin receptors after long-term treatment of rats

with fluoxetine," Research Communications in Chemical Pathology and Pharma¬

cology 32 (1981): 41-51.

38. J. Wamsley, "Receptor alterations associated with serotonergic agents," Journal of

Clinical Psychiatry 48, suppl. (1987): 19-25.

368

NOTES

39. A. Schatzberg, Textbook of Psychopharmacology (Washington, DC: American

Psychiatric Press, 1995), 8.

40. C. Montigny, "Modification of serotonergic neuron properties by long-term treat¬

ment with serotonin reuptake blockers," Journal of Clinical Psychiatry 51, suppl. B

(1990): 4-8.

41. D. Wong, "Subsensitivity of serotonin receptors after long-term treatment of rats

with fluoxetine," Research Communications in Chemical Pathology and Pharma¬

cology 32 (1981): 41-51.

42. C. Montigny, "Modification of serotonergic neuron properties by long-term treat¬

ment with serotonin reuptake blockers," Journal of Clinical Psychiatry 51, suppl. B

(1990): 4-8.

43. R. Fuller, "Inhibition of serotonin reuptake," Federation Proceedings 36 (1977):

2154-58.

44. B. Jacobs, "Serotonin and behavior," Journal of Clinical Psychiatry 52, suppl.

(1991): 151-62.

45. Schatzberg, Textbook of Psychopharmacology, 619.

46. S. Hyman, "Initiation and adaptation: A paradigm for understanding psychotropic

drug action," American Journal of Psychiatry 153 (1996): 151-61.

Chapter 6: A Paradox Revealed

1. E. Stip, "Happy birthday neuroleptics!" European Psychiatry 17 (2002): 115-19.

2. M. Boyle, "Is schizophrenia what it was?" Journal of the History of Behavioral

Science 26 (1990): 323-33; M. Boyle, Schizophrenia: A Scientific Delusion? (New

York: Routledge, 1990).

3. P. Popenoe, "In the melting pot," Journal of Heredity 14 (1923): 223.

4. J. Cole, editor. Psychopharmacology (Washington, DC: National Academy of Sci¬

ences, 1959), 142.

5. Ibid, 386-87.

6. N. Lehrman, "Follow-up of brief and prolonged psychiatric hospitalization," Com¬

prehensive Psychiatry 2 (1961): 227-40.

7. R. Warner, Recovery from Schizophrenia (Boston: Routledge & Kegan Paul, 1985),

74.

8. L. Epstein, "An approach to the effect of ataraxic drugs on hospital release rates,"

American Journal of Psychiatry 119 (1962): 246-61.

9. C. Silverman, The Epidemiology of Depression (Baltimore: Johns Hopkins Press,

1968), 139.

10. J. Swazey, Chlorpromazine in Psychiatry (Cambridge, MA: MIT Press, 1974), 247.

11. Cole, Psychopharmacology, 144,285.

12. Ibid, 285.

13. Ibid, 347.

14. R. Baldessarini, Chemotherapy in Psychiatry (Cambridge, MA: Harvard University

Press, 1977), 29.

15. A. Schatzberg, editor. Textbook of Psychopharmacology (Washington, DC:

American Psychiatric Press, 1995), 624.

NOTES

369

16. P. Gilbert, "Neuroleptic withdrawal in schizophrenic patients," Archives of General

Psychiatry 52 (1995): 173-88.

17. J. Geddes, "Prevention of relapse," New England Journal of Medicine 346 (2002):

56-58.

18. L. Dixon, "Conventional antipsychotic medications for schizophrenia." Schizophre¬

nia Bulletin 21 (1995): 567-77.

19. Stip, "Happy birthday, neuroleptics!"

20. N. Schooler, "One year after discharge," American journal of Psychiatry 123

(1967): 986-95.

21. R. Prien, "Discontinuation of chemotherapy for chronic schizophrenics," Hospital

and Community Psychiatry 22 (1971): 20-23.

22. G. Gardos and J. Cole, "Maintenance antipsychotic therapy: is the cure worse than

the disease?" American journal of Psychiatry 133 (1977): 32-36.

23. G. Gardos and J. Cole, "Withdrawal syndromes associated with antipsychotic

drugs," American Journal of Psychiatry 135 (1978): 1321-24. Also see Gardos and

Cole, "Maintenance antipsychotic therapy."

24. J. Bockoven, "Comparison of two five-year follow-up studies," American Journal of

Psychiatry 132 (1975): 796-801.

25. W. Carpenter, "The treatment of acute schizophrenia without drugs," American

Journal of Psychiatry 134 (1977): 14-20.

26. M. Rappaport, "Are there schizophrenics for whom drugs may be unnecessary or

contraindicated?" International Pharmacopsychiatry 13 (1978): 100-11.

27. S. Mathews, "A non-neuroleptic treatment for schizophrenia," Schizophrenia Bul¬

letin 5 (1979): 322-32.

28. J. Bola, "Treatment of acute psychosis without neuroleptics," Journal of Nervous

and Mental Disease 191 (2003): 219-29.

29. Carpenter, "The treatment of acute schizophrenia."

30. G. Paul, "Maintenance psychotropic drugs in the presence of active treatment pro¬

grams," Archives of General Psychiatry 27 (1972): 106-14.

31. T. Van Putten, "The board and care home: does it deserve a bad press?" Hospital

and Community Psychiatry 30 (1979): 461-64.

32. Gardos and Cole, "Maintenance antipsychotic therapy."

33. P. Deniker, "Are the antipsychotic drugs to be withdrawn?" in C. Shagass, editor.

Biological Psychiatry (New York: Elsevier, 1986), 1-9.

34. G. Chouinard, "Neuroleptic-induced supersensitivity psychosis," American Journal

of Psychiatry 135 (1978): 1409-10.

35. G. Chouinard, "Neuroleptic-induced supersensitivity psychosis: Clinical and phar¬

macologic characteristics," American Journal of Psychiatry 137 (1980): 16-20.

36. G. Chouinard, "Neuroleptic-induced supersensitivity psychosis, the 'Hump Course,'

and tardive dyskinesia," Journal of Clinical Psychopharmacology 2 (1982): 143-44.

37. G. Chouinard, "Severe cases of neuroleptic-induced supersensitivity psychosis,"

Schizophrenia Research 5 (1991): 21-33.

38. P. Muller, "Dopaminergic supersensitivity after neuroleptics," Psychopharmacology

60 (1978): 1-11.

370

NOTES

39. L. Martensson, "Should neuroleptic drugs be banned?" Proceedings of the World

Federation of Mental Health Conference in Copenhagen, 1984, accessed via

www.larsmartensson.com, 10/30/08.

40. P. Breggin, Brain Disabling Treatments in Psychiatry (New York: Springer Publish¬

ing Company, 1997), 60.

41. S. Snyder, Drugs and the Brain (New York: Scientific American Library, 1986), 88.

42. C. Harding, "The Vermont longitudinal study of persons with severe mental ill¬

ness," American journal of Psychiatry 144 (1987): 727-34; C. Harding, "The

Vermont longitudinal study of persons with severe mental illness, II," American

Journal of Psychiatry 144 (1987): 727-35.

43. P. McGuire, "New hope for people with schizophrenia," APA Monitor 31 (February

2000 ).

44. C. Harding, "Empirical correction of seven myths about schizophrenia with

implications for treatment," Acta Psychiatrica Scandinavica 384, suppl. (1994):

14-16.

45. A. Jablensky, "Schizophrenia: manifestations, incidence and course in different cul¬

tures," Psychological Medicine 20, monograph (1992): 1-95.

46. Ibid. See tables on page 60 for medication usage by individual centers; see table on

page 64 for medication usage by developing and developed countries.

47. K. Hopper, "Revisiting the developed versus developing country distinction in

course and outcome in schizophrenia," Schizophrenia Bulletin 26 (2000): 835-46.

48. J. Wade, "Tardive dyskinesia and cognitive impairment," Biological Psychiatry 22

(1987): 393-95.

49. M. Myslobodsky, "Central determinants of attention and mood disorder in tardive

dyskinesia," Brain and Cognition 23 (1993): 56-70.

50. H. Wisniewski, "Neurofibrillary pathology in brains of elderly schizophrenics

treated with neuroleptics," Alzheimer Disease and Associated Disorders 8 (1994):

211-27.

51. M. Chakos, "Increase in caudate nuclei volumes of first-episode schizophrenic pa¬

tients taking antipsychotic drugs," American Journal of Psychiatry 151 (1994):

1430-36; A. Madsen, "Neuroleptics in progressive structural brain abnormalities in

psychiatric illness," Lancet 352 (1998): 784-85; R. Gur, "A follow-up of magnetic

resonance imaging study of schizophrenia," Archives of General Psychiatry 55

(1998): 145-52.

52. R. Gur, "Subcortical MRI volumes in neuroleptic-naive and treated patients with

schizophrenia," American Journal of Psychiatry 155 (1998): 1711-17.

53. P. Seeman, "Dopamine supersensitivity correlates with Dz HIGH states, implying

many paths to psychosis," Proceedings of the National Academy of Science 102

(2005): 3513-18.

54. B. Ho, "Progressive structural brain abnormalities and their relationship to clinical

outcome," Archives of General Psychiatry 60 (2003): 585-94.

55. N. Andreasen, "Longitudinal changes in neurocognition during the first decade of

schizophrenia illness," International Congress on Schizophrenia Research (2005):

348.

NOTES

371

56. C. Dreifus, "Using imaging to look at changes in the brain," New York Times,

September 16, 2008.

57. T. McGlashan, "Rationale and parameters for medication-free research in psy¬

chosis," Schizophrenia Bulletin 32 (2006): 300-302.

58. M. Harrow, "Factors involved in outcome and recovery in schizophrenia patients

not on antipsychotic medications," Journal of Nervous and Mental Disease 195

(2007): 406-14.

59. National Institute of Mental Health, "The Numbers Count," accessed at

www.nimh.nih.gov on 3/7/2008.

Chapter 7: The Benzo Trap

1. S. Garfield, "Valium's 40th Birthday," Observer, February 2, 2003.

2. E. Shorter, A History of Psychiatry (New York: John Wiley & Sons, 1997), 161,

181.

3. A. Tone, The Age of Anxiety (New York: Basic Books, 2009), 15.

4. American Psychiatry Association, Diagnostic and Statistical Manual of Mental

Disorders (1952), 31.

5. C. Silverman, The Epidemiology of Depression (Baltimore: Johns Hopkins Press,

1968), 139.

6. L. Hollister, "Drugs for emotional disorders," Journal of the American Medical As¬

sociation 234 (1975): 942-47.

7. F. Ayd Jr., Discoveries in Biological Psychiatry (Philadelphia: Lippincott, 1970), 127.

8. D. Greenblatt, "Meprobamate: a study of irrational drug use," American Journal of

Psychiatry 127 (1971): 33-39.

9. C. Essig, "Addiction to nonbarbiturate sedative and tranquillizing drugs," Clinical

Pharmacology & Therapeutics 5 (1964): 334-43.

10. "Letdown for Miltown," Time, April 30, 1965.

11. Tone, The Age of Anxiety, 171.

12. M. Smith, Small Comfort (New York: Praeger, 1985), 78.

13. Tone, The Age of Anxiety, 172.

14. G. Cant, "Valiumania," New York Times, February 1, 1976.

15. R. Hughes, The Tranquilizing of America (New York: Harcourt Brace Jovanovich,

1979), 8.

16. Tone, The Age of Anxiety, 176.

17. Committee on the Review of Medicines, "Systematic review of the benzodi¬

azepines," British Medical Journal 280 (1980): 910-12.

18. Editorial, "Benzodiazepines on trial," British Medical Journal 288 (1984): 1101-12.

19. Smith, Small Comfort, 32.

20. S. Stahl, "Don't ask, don't tell, but benzodiazepines are still the leading treatments

for anxiety disorder," Journal of Clinical Psychiatry 63 (2002): 756-67.

21. IMS Health, "Top therapeutic classes by U.S. dispensed prescriptions," 2006 and

2007 reports.

22. K. Solomon, "Pitfalls and prospects in clinical research on antianxiety drugs,"

Journal of Clinical Psychiatry 39 (1978): 823-31.

372

NOTES

23. A. Shapiro, "Diazepam: how much better than placebo?" Journal of Psychiatric Re¬

search 17 (1983): 51-73.

24. C. Gudex, "Adverse effects of benzodiazepines," Social Science & Medicine 33

(1991): 587-96.

25. J. Martin, "Benzodiazepines in generalized anxiety disorder," Journal of Psy¬

chopharmacology 21 (2007): 774-82.

26. Malcolm Lader interview, January 12, 2009.

27. B. Maletzky, "Addiction to diazepam," International Journal of Addictions 11

(1976): 95-115.

28. A. Kales, "Rebound insomnia," Science 201 (1978): 1039-40.

29. H. Petursson, "Withdrawal from long-term benzodiazepine treatment," British

Medical Journal 283 (1981): 643-35.

30. H. Ashton, "Benzodiazepine withdrawal," British Medical Journal 288 (1984):

1135-40.

31. H. Ashton, "Protracted withdrawal syndromes from benzodiazepines," Journal of

Substance Abuse Treatment 9 (1991): 19-28.

32. P. Cowen, "Abstinence symptoms after withdrawal of tranquillising drugs," Lancet

2, 8294(1982): 360-62.

33. H. Ashton, "Benzodiazepine withdrawal," British Medical Journal 288 (1984):

1135-40.

34. H. Ashton, Benzodiazepines: How They Work and How to Withdraw (Newcastle

upon Tyne: University of Newcastle, 2000), 42.

35. H. Ashton, "Protracted withdrawal syndromes from benzodiazepines," Journal of

Substance Abuse Treatment 9 (1991): 19-28.

36. K. Rickels, "Long-term benzodiazepine users 3 years after participation in a discon¬

tinuation program," American Journal of Psychiatry 148 (1991): 757-61.

37. K. Rickels, "Psychomotor performance of long-term benzodiazepine users before,

during, and after benzodiazepine discontinuation," Journal of Clinical Psychophar¬

macology 19 (1999): 107-13.

38. S. Patten, "Self-reported depressive symptoms following treatment with cortico¬

steroids and sedative-hypnotics," International Journal of Psychiatry in Medicine 26

(1995): 15-24.

39. Ashton, Benzodiazepines, 8.

40. A. Pelissolo, "Anxiety and depressive disorders in 4,425 long term benzodiazepine

users in general practice," Encephale 33 (2007): 32-38.

41. Hughes, The Tranquilizing of America, 17.

42. S. Golombok, "Cognitive impairment in long-term benzodiazepine users," Psycho¬

logical Medicine 18 (1988): 365-74.

43. M. Barker, "Cognitive effects of long-term benzodiazepine use," CNS Drugs 18

(2004): 37-48.

44. WHO Review Group, "Use and abuse of benzodiazepines," Bulletin of the World

Health Organization 61 (1983): 551-62.

45. Maletzky, "Addiction to diazepam."

NOTES

373

46. R. Caplan, "Social effects of diazepam use/' Social Science & Medicine 21 (1985):

887-98.

47. H. Ashton, "Tranquillisers," British Journal of Addiction 84 (1989): 541-46.

48. Ashton, Benzodiazepines , 12.

49. Stevan Gressitt interview, January 9, 2009.

50. U.S. Department of Health 6c Human Services, SAMHSA, Mental Health , United

States (2002).

51. Government Accountability Office, Young Adults with Serious Mental Illness , June

2008.

52. R. Vasile, "Results of a naturalistic longitudinal study of benzodiazepine and SSRI

use in the treatment of generalized anxiety disorder and social phobia," Depression

and Anxiety 22 (2005): 59-67.

53. Malcolm Lader interview, January 12, 2009.

Chapter 8: An Episodic Illness Turns Chronic

1. C. Dewa, "Depression in the workplace," A Report to the Ontario Roundtable on

Appropriate Prescribing, November 2001.

2. A. Solomon, The Noonday Demon (New York: Simon & Schuster, 2001), 289.

3. C. Goshen, editor. Documentary History of Psychiatry (New York: Philosophical

Library, 1967), 118-20.

4. Solomon, The Noonday Demon , 286.

5. E. Wolpert, editor, Manic-Depressive Illness (New York: International Universities

Press, 1997), 34.

6. C. Silverman, The Epidemiology of Depression (Baltimore: Johns Hopkins Press,

1968), 44, 139. The first-admission and residence data in Silverman's book is for all

manic-depressive patients; the unipolar patients comprised about 75 percent of that

total.

7. Ibid, 79, 142.

8. E Ayd, Recognizing the Depressed Patient (New York: Grune & Stratton, 1961),

13.

9. A. Zis, "Major affective disorder as a recurrent illness," Archives of General Psy¬

chiatry 36 (1979): 835-39.

10. G. Winokur, Manic Depressive Illness (St. Louis: The C.V. Mosby Company, 1969),

19-20.

11. T. Rennie, "Prognosis in manic-depressive psychoses," American Journal of Psychi¬

atry 98 (1941): 801-14. See table on page 811.

12. G. Lundquist, "Prognosis and course in manic-depressive psychoses," Acta Psychi-

atrica Scandinavica , suppl. 35 (1945): 7-93.

13. D. Schuyler, The Depressive Spectrum (New York: Jason Aronson, 1974), 49.

14. J. Cole, "Therapeutic efficacy of antidepressant drugs," Journal of the American

Medical Association 190 (1964): 448-55.

15. N. Kline, "The practical management of depression," Journal of the American

Medical Association 190 (1964): 122-30.

374

NOTES

16. Winokur, Manic Depressive Illness, 19.

17. Schuyler, The Depressive Spectrum, 47.

18. Medical Research Council, "Clinical trial of the treatment of depressive illness,"

British Medical Journal 1 (1965): 881-86.

19. A. Smith, "Studies on the effectiveness of antidepressant drugs," Psychopharmacol¬

ogy Bulletin 5 (1969): 1-53.

20. A. Raskin, "Differential response to chlorpromazine, imipramine, and placebo,"

Archives of General Psychiatry 23 (1970): 164-73.

21. R. Thomson, "Side effects and placebo amplification," British Journal of Psychiatry

140(1982): 64-68.

22. I. Elkin, "NIMH treatment of depression collaborative research program," Archives

of General Psychiatry 47 (1990): 682-88.

23. A. Khan, "Symptom reduction and suicide risk in patients treated with placebo in

antidepressant clinical trials," Archives of General Psychiatry 57 (2000): 311-17.

24. E. Turner, "Selective publication of antidepressant trials and its influence on appar¬

ent efficacy," New England Journal of Medicine 358 (2008): 252-60.

25. I. Kirsch, "Initial severity and antidepressant benefits," PLoS Medicine 5 (2008):

260-68.

26. G. Parker, "Antidepressants on trial," British Journal of Psychiatry 194 (2009): 1-3.

27. C. Barbui, "Effectiveness of paroxetine in the treatment of acute major depression in

adults," Canadian Medical Association Journal 178 (2008): 296-305.

28. J. Ioannidis, "Effectiveness of antidepressants," Philosophy, Ethics, and Humanities

in Medicine 3 (2008): 14.

29. Hypericum Trial Study Group, "Effect of Hypericum perforatum in major depres¬

sive disorder," Journal of the American Medical Association 287 (2002): 1807-14.

30. J.D. Van Scheyen, "Recurrent vital depressions," Psychiatria, Neurologia, Neuro-

chirurgia76 (1973): 93-112.

31. Ibid.

32. R. Mindham, "An evaluation of continuation therapy with tricyclic antidepressants

in depressive illness," Psychological Medicine 3 (1973): 5-17.

33. M. Stein, "Maintenance therapy with amitriptyline," American Journal of Psychia¬

try 137(1980): 370-71.

34. R. Prien, "Drug therapy in the prevention of recurrences in unipolar and bipolar af¬

fective disorders," Archives of General Psychiatry 41 (1984): 1096-1104. See table

6 and figure 2.

35. M. Shea, "Course of depressive symptoms over follow-up," Archives of General

Psychiatry 49 (1992): 782-87.

36. A. Viguera, "Discontinuing antidepressant treatment in major depression," Harvard

Review of Psychiatry 5 (1998): 293-305.

37. P. Haddad, "Antidepressant discontinuation reactions," British Medical Journal 316

(1998): 1105-6.

38. G. Fava, "Do antidepressant and antianxiety drugs increase chronicity in affective

disorders?" Psychotherapy and Psychosomatics 61 (1994): 125-31.

NOTES

375

39. G. Fava, "Can long-term treatment with antidepressant drugs worsen the course of

depression?" Journal of Clinical Psychiatry 64 (2003): 123-33.

40. Ibid.

41. G. Fava, "Holding on: depression, sensitization by antidepressant drugs, and the

prodigal experts," Psychotherapy and Psychosomatics 64 (1995): 57-61; G. Fava,

"Potential sensitizing effects of antidepressant drugs on depression," CNS Drugs 12

(1999): 247-56.

42. R. Baldessarini, "Risks and implications of interrupting maintenance psychotropic

drug therapy," Psychotherapy and Psychosomatics 63 (1995): 137-41.

43. R. El-Mallakh, "Can long-term antidepressant use be depressogenic?" Journal of

Clinical Psychiatry 60 (1999): 263.

44. "Editorial sparks debate on effects of psychoactive drugs," Psychiatric News, May

20, 1994.

45. Consensus Development Panel, "Mood disorders," American Journal of Psychiatry

142 (1985): 469-76.

46. R. Hales, editor. Textbook of Psychiatry (Washington, DC: American Psychiatric

Press, 1999), 525.

47. J. Geddes, "Relapse prevention with antidepressant drug treatment in depressive

disorders," Lancet 361 (2003): 653-61.

48. L. Judd, "Does incomplete recovery from first lifetime major depressive episode her¬

ald a chronic course of illness?" American Journal of Psychiatry 157 (2000): 1501-4.

49. R. Tranter, "Prevalence and outcome of partial remission in depression," Journal of

Psychiatry and Neuroscience 27 (2002): 241-47.

50. Hales, Textbook of Psychiatry, 547.

51. J. Rush, "One-year clinical outcomes of depressed public sector outpatients," Bio¬

logical Psychiatry 56 (2004): 46-53.

52. Ibid.

53. D. Warden, "The star*d project results," Current Psychiatry Reports 9 (2007):

449-59.

54. NIMH, Depression (2007): 3. (NIH Publication 07-3561.)

55. D. Deshauer, "Selective serotonin reuptake inhibitors for unipolar depression,"

Canadian Medical Association Journal 178 (2008): 1293-1301.

56. C. Ronalds, "Outcome of anxiety and depressive disorders in primary care," British

Journal of Psychiatry 171 (1997): 427-33.

57. E. Weel-Baumgarten, "Treatment of depression related to recurrence," Journal of

Clinical Pharmacy and Therapeutics 25 (2000): 61-66.

58. S. Patten, "The impact of antidepressant treatment on population health," Popula¬

tion Health Metrics 2 (2004): 9.

59. D. Goldberg, "The effect of detection and treatment on the outcome of major de¬

pression in primary care," British Journal of General Practice 48 (1998): 1840-44.

60. Dewa, "Depression in the workplace."

61. W. Coryell, "Characteristics and significance of untreated major depressive disor¬

der," American Journal of Psychiatry 152 (1995): 1124-29.

376

NOTES

62. J. Moncrieff, "Trends in sickness benefits in Great Britain and the contribution of

mental disorders," Journal of Public Health Medicine 22 (2000): 59-67.

63. T. Helgason, "Antidepressants and public health in Iceland," British Journal of Psy¬

chiatry 184 (2004): 157-62.

64. R. Rosenheck, "The growth of psychopharmacology in the 1990s," International

Journal of Law and Psychiatry 28 (2005): 467-83.

65. M. Posternak, "The naturalistic course of unipolar major depression in the absence

of somatic therapy," Journal of Nervous and Mental Disease 194 (2006): 324-49.

66. Ibid. Also see M. Posternak, "Untreated short-term course of major depression,"

Journal of Affective Disorders 66 (2001): 139-46.

67. J. Cole, editor. Psychopharmacology (Washington, DC: National Academy of Sci¬

ences, 1959), 347.

68. NIMH, "The numbers count," accessed at www.nimh.nih.gov on 3/7/2008; W. Eaton,

"The burden of mental disorders," Epidemiologic Reviews 30 (2008): 1-14.

69. M. Fava, "A cross-sectional study of the prevalence of cognitive and physical symp¬

toms during long-term antidepressant treatment," Journal of Clinical Psychiatry 67

(2006): 1754-59.

70. M. Kalia, "Comparative study of fluoxetine, sibutramine, sertraline and defenflu¬

ramine on the morphology of serotonergic nerve terminals using serotonin immuno-

histochemistry," Brain Research 858 (2000): 92-105. Also see press release by

Thomas Jefferson University Hospital, "Jefferson scientists show several serotonin¬

boosting drugs cause changes in some brain cells," 2/29/2000.

Chapter 9: The Bipolar Boom

1. D. Healy, Mania (Baltimore: Johns Hopkins University Press, 2008), 16, 41, 43.

2. I calculated these estimates by applying the 25 percent figure to the 1955 data on

patients in state and county mental hospitals with a diagnosis of manic-depressive

illness.

3. C. Silverman, The Epidemiology of Depression (Baltimore: Johns Hopkins Univer¬

sity Press, 1968), 139.

4. G. Winokur, Manic Depressive Illness (St. Louis: The C.V. Mosby Company, 1969),

19.

5. F. Wertham, "A group of benign chronic psychoses," American Journal of Psychia¬

try 9 (1929): 17-78.

6. G. Lundquist, "Prognosis and course in manic-depressive psychoses," Acta Psychi-

atrica Scandinavica, suppl. 35 (1945): 7-93.

7. M. Tsuang, "Long-term outcome of major psychoses," Archives of General Psychi¬

atry 36 (1979): 1295-1301.

8. Winokur, Manic Depressive Illness, 21.

9. NIMH, The Numbers Count: Mental Disorders in America, accessed at

www.nimh.nih.gov on 3/7/2008.

10. C. Baethge, "Substance abuse in first-episode bipolar I disorder," American Journal

of Psychiatry 162 (2005): 1008-10; E. Frank, "Association between illicit drug and

NOTES

377

alcohol use and first manic episode," Pharmacology Biochemistry and Behavior 86

(2007): 395-400.

11. S. Strakowski, "The effects of antecedent substance abuse on the development of

first-episode psychotic mania," Journal of Psychiatric Research 30 (1996): 59-68.

12. J. Goldberg, "Overdiagnosis of bipolar disorder among substance use disorder inpa¬

tients with mood instability," Journal of Clinical Psychiatry 69 (2008): 1751-57.

13. M. Van Laar, "Does cannabis use predict the first incidence of mood and anxiety

disorders in the adult population?" Addiction 102 (2007): 1251-60.

14. G. Crane, "The psychiatric side effects of iproniazid," American Journal of Psychia¬

try 112 (1956): 494-501.

15. J. Angst, "Switch from depression to mania," Psych op athology 18 (1985): 140-54.

16. American Psychiatric Association, Practice Guidelines for Major Depressive Disor¬

der in Adults (Washington, DC: APA, 1993), 22.

17. A. Martin, "Age effects on antidepressant-induced manic conversion," Archives of

Pediatrics & Adolescent Medicine 158 (2004): 773-80.

18. J. Goldberg, "Risk for bipolar illness in patients initially hospitalized for unipolar

depression," American Journal of Psychiatry 158 (2001): 1265-70.

19. R. El-Mallakh, "Use of antidepressants to treat depression in bipolar disorder," Psy¬

chiatric Services 53 (2002): 58-84.

20. Interview with Fred Goodwin, "Advances in the diagnosis and treatment of bipolar

disorder," Primary Psychiatry, accessed via Internet on 3/6/09 at primarypsychia-

try.com .

21. G. Fava, "Can long-term treatment with antidepressant drugs worsen the course of

depression?" Journal of Clinical Psychiatry 64 (2003): 123-33.

22. L. Judd, "The prevalence and disability of bipolar spectrum disorders in the US pop¬

ulation," Journal of Affective Disorders 73 (2003): 123-31.

23. J. Angst, "Toward a re-definition of subthreshold bipolarity," Journal of Affective

Disorders 73 (2003): 133-46.

24. Ibid; Judd, "The prevalence and disability."

25. R. Fieve, Moodswing (New York: William Morrow and Company, 1975), 13.

26. For a history of lithium, see Healy, Mania, and J. Moncrieff, The Myth of the Chem¬

ical Cure (New York: Palgrave MacMillan, 2008).

27. S. Tyrer, "Lithium in the treatment of mania," Journal of Affective Disorders 8

(1985): 251-57.

28. J. Baker, "Outcomes of lithium discontinuation," Lithium 5 (1994): 187-92.

29. R. Baldessarini, "Discontinuing lithium maintenance treatment in bipolar disor¬

ders," Bipolar Disorders 1 (1999): 17-24.

30. G. Faedda, "Outcome after rapid v. gradual discontinuation of lithium treatment in

bipolar disorders," Archives of General Psychiatry 50 (1993): 448-55.

31. J. Himmelhoch, "On the failure to recognize lithium failure," Psychiatric Annals 24

(1994): 241-50.

32. J. Moncrieff, The Myth of the Chemical Cure (London: Palgrave Macmillan, 2008),

199.

378

NOTES

33. G. Goodwin, "Recurrence of mania after lithium withdrawal," British Journal of

Psychiatry 164 (1994): 149-52.

34. H. Markar, "Efficacy of lithium prophylaxis in clinical practice," British Journal of

Psychiatry 155 (1989): 496-500; J. Moncrieff, "Lithium revisited," British Journal

of Psychiatry 167 (1995): 569-74.

35. J. Goldberg, "Lithium treatment of bipolar affective disorders under naturalistic fol¬

lowup conditions," Psychopharmacology Bulletin 32 (1996): 47-54.

36. M. Gitlin, "Relapse and impairment in bipolar disorder," American Journal ofPsy-

.chiatry 152 (1995): 1635-40.

37. J. Moncrieff, "Lithium: evidence reconsidered," British Journal of Psychiatry 171

(1997): 113-19.

38. F. Goodwin, Manic-Depressive Illness (New York: Oxford University Press, 1990),

647.

39. A. Zis, "Major affective disorder as a recurrent illness," Archives of General

Psychiatry 36 (1979): 835-39.

40. A. Koukopoulos, "Rapid cyclers, temperament, and antidepressants," Comprehen¬

sive Psychiatry 24 (1983): 249-58.

41. N. Ghaemi, "Diagnosing bipolar disorder and the effect of antidepressants," Jour¬

nal of Clinical Psychiatry 61 (2000): 804-809.

42. N. Ghaemi, "Antidepressants in bipolar disorder," Bipolar Disorders 5 (2003):

421-33.

43. R. El-Mallakh, "Use of antidepressants to treat depression in bipolar disorder," Psy¬

chiatric Services 53 (2002): 580-84.

44. A. Koukopoulos, "Duration and stability of the rapid-cycling course," Journal of

Affective Disorders 72 (2003): 75-85.

45. R. El-Mallakh, "Antidepressant-associated chronic irritable dysphoria in bipolar

disorder," Journal of Affective Disorders 84 (2005): 267-72.

46. N. Ghaemi, "Treatment of rapid-cycling bipolar disorder," American Journal of

Psychiatry 165 (2008): 300-301.

47. C. Schneck, "The prospective course of rapid-cycling bipolar disorder," American

Journal of Psychiatry 165 (2008): 370-77.

48. L. Judd, "The long-term natural history of the weekly symptomatic status of bipolar

I disorder," Archives of General Psychiatry 59 (2002): 530-37.

49. L. Judd, "A prospective investigation of the natural history of the long-term weekly

symptomatic status of bipolar II disorder," Archives of General Psychiatry 60

(2003): 261-69.

50. R. Joffe, "A prospective, longitudinal study of percentage of time spent ill in patients

with bipolar I or bipolar II disorders," Bipolar Disorders 6 (2004): 62-66.

51. R. Post, "Morbidity in 258 bipolar outpatients followed for 1 year with daily

prospective ratings on the NIMH life chart method," Journal of Clinical Psychiatry

64 (2003): 680-90.

52. L. Judd, "Residual symptom recovery from major affective episodes in bipolar dis¬

orders and rapid episode relapse/recurrence," Archives of General Psychiatry 65

(2008): 386-94.

NOTES

379

53. C. Zarate, "Functional impairment and cognition in bipolar disorder," Psychiatric

Quarterly 71 (2000): 309-29.

54. Gitlin, "Relapse and impairment."

55. R Keck, "12-month outcome of patients with bipolar disorder following hospital¬

ization for a manic or a mixed episode," American journal of Psychiatry 155

(1998): 646-52.

56. D. Kupfer, "Demographic and clinical characteristics of individuals in a bipolar

disorder case registry," journal of Clinical Psychiatry 63 (2002): 120-25.

57. N. Huxley, "Disability and its treatment in bipolar disorder patients," Bipolar Dis¬

orders 9 (2007): 183-96.

58. T. Goldberg, "Contrasts between patients with affective disorders and patients with

schizophrenia on a neuropsychological test battery," American journal of Psychia¬

try 150 (1993): 1355-62.

59. J. Zihl, "Cognitive deficits in schizophrenia and affective disorders," Acta Psychi-

atrica Scandinavica 97 (1998): 351-57.

60. F. Dickerson, "Outpatients with schizophrenia and bipolar I disorder," Psychiatry

Research 102 (2001): 21-27.

61. G. Malhi, "Neuropsychological deficits and functional impairment in bipolar de¬

pression, hypomania and euthymia," Bipolar Disorders 9 (2007): 114-25.

62. V. Balanza-Martinez, "Persistent cognitive dysfunctions in bipolar I disorder and

schizophrenic patients," Psychotherapy and Psychosomatics 74 (2005): 113-19;

A Martinez-Aran, "Functional outcome in bipolar disorder," Bipolar Disorders 9

(2007): 103-13.

63. M. Pope, "Determinants of social functioning in bipolar disorder," Bipolar Disor¬

ders 9 (2007): 38-44.

64. C. Zarate, "Antipsychotic drug side effect issues in bipolar manic patients," Journal

of Clinical Psychiatry 61, suppl. 8 (2000): 52-61.

65. C. Zarate, "Functional impairment and cognition in bipolar disorder," Psychiatric

Quarterly 71 (2000): 309-29.

66. D. Kupfer, "The increasing medical burden in bipolar disorder," journal of the

American Medical Association 293 (2005): 2528-30.

67. L. Citrome, "Toward convergence in the medication treatment of bipolar disorder

and schizophrenia," Harvard Review of Psychiatry 13 (2005): 28-42.

68. Huxley, "Disability and its treatment."

69. M. Harrow, "Factors involved in outcome and recovery in schizophrenia patients

not on antipsychotic medications," Journal of Nervous and Mental Disorders 195

(2007): 406-14.

70. W. Eaton, "The burden of mental disorders," Epidemiology Review 30 (2008):

1-14.

Chapter 10: An Epidemic Explained

1. Interview with Amy Upham, June 14, 2009.

2. M. Morgan, "Prospective analysis of premature mortality in schizophrenia in rela¬

tion to health service engagement," Psychiatry Research 117 (2003): 127-35;

3 8 o

NOTES

C. Colton, "Congruencies in increased mortality rates, years of potential life lost,

and causes of death among public mental health clients in eight states," Preventing

Chronic Disease 3 (April 2006).

3. S. Saha, "A systematic review of mortality in schizophrenia," Archives of General

Psychiatry 64 (2007): 1123-31; L. Appleby, "Sudden unexplained death in psychi¬

atric in-patients," British Journal of Psychiatry 176 (2000): 405-406; M. Jouka-

maa, "Schizophrenia, neuroleptic medication, and mortality," British Journal of

Psychiatry 188 (2006): 122-27.

Chapter 11: The Epidemic Spreads to Children

1. B. Carey, "What's wrong with a child? Psychiatrists often disagree," New York

Times , November 11, 2006.

2. R. Kessler, "Mood disorders in children and adolescents," Biological Psychiatry 49

(2001): 1002-14.

3. J. O'Neal, Child and Adolescent Psychopharmacology Made Simple (Oakland, CA:

New Harbinger Publications, 2006), 6.

4. R. Mayes, Medicating Children (Cambridge, MA: Harvard University Press, 2009),

46.

5. G. Jackson, "Postmodern psychiatry," unpublished paper, September 2, 2002.

6. Mayes, Medicating Children, 54.

7. Ibid, 61.

8. R. Mayes, "ADHD and the rise in stimulant use among children," Harvard Review

of Psychiatry 16 (2008): 151-66.

9. G. Golden, "Role of attention deficit hyperactivity disorder in learning disabilities,"

Seminars in Neurology 11 (1991): 35-41.

10. NIH Consensus Development Conference statement, "Diagnosis and treatment of

attention deficit hyperactivity disorder," November 16-18, 1998.

11. P. Breggin, Talking Back to Ritalin (Cambridge, MA: Perseus Publishing, 2001),

180.

12. S. Hyman, "Initiation and adaptation: a paradigm for understanding psychotropic

drug action," American Journal of Psychiatry 153 (1996): 151-61.

13. Breggin, Talking Back to Ritalin , 83.

14. H. Rie, "Effects of methylphenidate on underachieving children," Journal of Con¬

sulting and Clinical Psychology 44 (1976): 250-60.

15. C. Cunningham, "The effects of methylphenidate on the mother-child interactions

of hyperactive identical twins," Developmental Medicine & Child Neurology 20

(1978): 634-42.

16. N. Fiedler, "The effects of stimulant drugs on curiosity behaviors of hyperactive

boys," Journal of Abnormal Child Psychology 11 (1983): 193-206.

17. T. Davy, "Stimulant medication and short attention span," Journal of Developmen¬

tal & Behavioral Pediatrics 10 (1989): 313-18.

18. D. Granger, "Perceptions of methylphenidate effects on hyperactive children's peer

interactions," Journal of Abnormal Child Psychology 21 (1993): 535-49.

NOTES

381

19. J. Swanson, "Effects of stimulant medication on learning in children with ADHD,"

Journal of Learning Disabilities 24 (1991): 219-30.

20. Breggin, Talking Back to Ritalin, 92.

21. J. Richters, "NIMH Collaborative Multisite Multimodal Treatment Study of Chil¬

dren with ADHD," Journal of the American Academy of Child & Adolescent Psy¬

chiatry 34 (1995): 987-1000.

22. T. Spencer, "Pharmacotherapy of attention-deficit hyperactivity disorder across the

life cycle," Journal of the American Academy of Child & Adolescent Psychiatry 35

(1996): 409-32.

23. E. Sleator, "How do hyperactive children feel about taking stimulants and will they

tell the doctor?" Clinical Pediatrics 21 (1982): 474-79.

24. D. Jacobvitz, "Treatment of attentional and hyperactivity problems in children with

sympathomimetic drugs," Journal of the American Academy of Child & Adolescent

Psychiatry 29 (1990): 677-88.

25. A. Sroufe, "Treating problem children with stimulant drugs," New England Journal

of Medicine 289 (1973): 407-13.

26. Ibid.

27. Rie, "Effects of methylphenidate."

28. R. Barkley, "Do stimulant drugs improve the academic performance of hyperkinetic

children?" Clinical Pediatrics 8 (1978): 137-46.

29. Swanson, "Effects of stimulant medication."

30. C. Whalen, "Stimulant pharmacotherapy for attention-deficit hyperactivity disor¬

ders," in S. Fishberg and R. Greenberg, eds.. From Placebo to Panacea (New York:

John Wiley & Sons, 1997), 329.

31. R. Schachar, "Attention-deficit hyperactivity disorder," Canadian Journal of Psychi¬

atry 47 (2002): 337-48.

32. Whalen, "Stimulant pharmacotherapy," 327.

33. P. Breggin, "Psychostimulants in the treatment of children diagnosed with ADHD,"

International Journal of Risk & Safety in Medicine 12 (1993): 3-35.

34. Ibid.

35. Richters, "NIMH Collaborative Multisite."

36. P. Jensen, "3-year follow-up of the NIMH MTA study," Journal of the American

Academy of Child & Adolescent Psychiatry 46 (2007): 989-1002. See chart on page

997 for medication use.

37. The MTA Cooperative Group, "A 14-month randomized clinical trial of treatment

strategies for attention-deficit/hyperactivity disorder," Archives of General Psychia¬

try 56 (1999): 1073-86.

38. Jensen, "3-year follow-up."

39. B. Molina, "Delinquent behavior and emerging substance use in the MTA at 36

months," Journal of the American Academy of Child & Adolescent Psychiatry 46

(2007): 1028-39.

40. B. Molina, "MTA at 8 years," Journal of the American Academy of Child & Ado¬

lescent Psychiatry 48 (2009): 484-500.

382

NOTES

41. C. Miranda, "ADHD drugs could stunt growth," Daily Telegraph (UK), November

12, 2007.

42. Breggin, Talking Back to Ritalin; K. Bolla, "The neuropsychiatry of chronic cocaine

abuse," Journal of Neuropsychiatry and Clinical Neurosciences 10 (1998): 280-89.

43. S. Castner, "Long-lasting psychotomimetic consequences of repeated low-dose am¬

phetamine exposure in rhesus monkeys," Neuropsychopharmacology 20 (1999):

10-28.

44. W. Carlezon, "Enduring behavioral effects of early exposure to methylphenidate in

rats," Biological Psychiatry 54 (2003): 1330-37.

45. C. Bolanos, "Methylphenidate treatment during pre- and periadolescence alters be¬

havioral responses to emotional stimuli at adulthood," Biological Psychiatry 54

(2003): 1317-29.

46. J. Zito, "Rising prevalence of antidepressants among US youths," Pediatrics 109

(2002): 721-27.

47. R. Fisher, Prom Placebo to Panacea (New York: John Wiley & Sons, 1997), 309.

48. T. Delate, "Trends in the use of antidepressants in a national sample of commercially

insured pediatric patients, 1998 to 2002," Psychiatric Services 55 (2004): 387-91.

49. Editorial, "Depressing research," Lancet 363 (2004): 1335.

50. T. Laughren, Memorandum, "Background comments for Feb. 2, 2004 meeting of

psychopharmacological drugs advisory committee," January 5, 2004. Accessed at

fda.gov .

51. J. Leo, "The SSRI trials in children," Ethical Human Psychology and Psychiatry 8

(2006): 29-41.

52. C. Whittington, "Selective serotonin reuptake inhibitors in childhood depression,"

Lancet 363 (2004): 1341-45.

53. Editorial, "Depressing research," Lancet 363 (2004): 1335.

54. J. Jureidini, "Efficacy and safety of antidepressants for children and adolescents,"

British Medical Journal (2004): 879-83.

55. T. Wilens, "A systematic chart review of the nature of psychiatric adverse events in

children and adolescents treated with selective serotonin reuptake inhibitors," Jour¬

nal of Child and Adolescent Psychopharmacology 13 (2003): 143-52.

56. T. Gualtieri, "Antidepressant side effects in children and adolescents," Journal of

Child and Adolescent Psychopharmacology 16 (2006): 147-57.

57. P. Breggin, Brain-Disabling Treatments in Psychiatry (New York: Springer Publish¬

ing Company, 2008), 153.

58. D. Papolos, The Bipolar Child (New York: Broadway Books, 2000), xiv.

59. C. Moreno, "National trends in the outpatient diagnosis and treatment of bipolar

disorder in youth," Archives of General Psychiatry 64 (2007): 1032-39.

60. J. Kluger, "Young and Bipolar," Time , August 19, 2002.

61. L. Lurie, "Psychoses in children," Journal of Pediatrics 36 (1950): 801-9.

62. Ibid.

63. B. Hall, "Our present knowledge about manic-depressive states in childhood," Ner¬

vous Child 9 (1952): 319-25.

NOTES

383

64. J. Anthony, "Manic-depressive psychosis in childhood," Journal of Child Psychol¬

ogy and Psychiatry 1 (1960): 53-72.

65. W. Weinberg, "Mania in childhood," American Journal of Diseases of Childhood

130(1976): 380-85.

66. R. DeLong, "Lithium carbonate treatment of select behavior disorders in children

suggesting manic-depressive illness," Journal of Pediatrics 93 (1978): 689-94.

67. M. Strober, "Bipolar illness in adolescents with major depression," Archives of

General Psychiatry 39 (1982): 549-55.

68. R Lewinsohn, "Bipolar disorders in a community sample of older adolescents," Jour¬

nal of the American Academy of Child & Adolescent Psychiatry 34 (1995): 454-63.

69. G. Carlson, "Manic symptoms in psychiatrically hospitalized children —what do

they mean?" Journal of Affective Disorders 51 (1998): 123-35.

70. J. Kluger, "Young and Bipolar."

71. D. Janowsky, "Proceedings: effect of intravenous d-amphetamine, 1-amphetamine

and methylphenidate in schizophrenics," Psychopharmacology Bulletin 19 (1974):

15-24.

72. E. Cherland, "Psychotic side effects of psychostimulants," Canadian Journal of

Psychiatry 44 (1999): 811-13.

73. K. Gelperin, "Psychiatric adverse events associated with drug treatment of ADHD,"

FDA, Center for Drug Evaluation and Research, March 3, 2006.

74. D. Papolos, "Bipolar disorder, co-occuring conditions, and the need for extreme

caution before initiating drug treatment," Bipolar Child Newsletter 1 (November

1999).

75. M. DelBello, "Prior stimulant treatment in adolescents with bipolar disorder," Bi¬

polar Disorders 3 (2001): 53-57.

76. J. Biederman, "Attention-deficit hyperactivity disorder and juvenile mania," Journal

of the American Academy of Child & Adolescent Psychiatry 35 (1996): 997-1008.

77. J. Jain, "Fluoxetine in children and adolescents with mood disorders," Journal of

Child & Adolescent Psychopharmacology 2 (1992): 259-65.

78. G. Emslie, "A double-blind, randomized, placebo-controlled trial of fluoxetine in

children and adolescents with depression," Archives of General Psychiatry 54

(1997): 1031-37.

79. P. Breggin, The Anti-Depressant Fact Book (Cambridge, MA: Perseus Publishing,

2001), 116.

80. A. Martin, "Age effects on antidepressant-induced manic conversion," Archives of

Pediatrics & Adolescent Medicine 158 (2004): 773-80.

81. G. Faedda, "Pediatric onset bipolar disorder," Harvard Review of Psychiatry 3

(1995): 171-95.

82. B. Geller, "Bipolar disorder at prospective follow-up of adults who had prepubertal

major depressive disorder," American Journal of Psychiatry 158 (2001): 125-27.

83. D. Cicero, "Antidepressant exposure in bipolar children," Psychiatry 66 (2003):

317-22.

84. D. Papolos. "Antidepressant-induced adverse effects in juvenile-onset bipolar

384

NOTES

disorder/' paper presented at the Fifth International Conference on Bipolar Disor¬

der, June 12-14, 2003, Pittsburgh, PA.

85. G. Faedda, "Pediatric bipolar disorder," Bipolar Disorders 6 (2004): 305-13.

86. M. Hellander, "Children with bipolar disorder," Journal of the American Academy

of Child & Adolescent Psychiatry 38 (1999): 495.

87. H. Marano, "Crisis on the campus," Psychology Today, May 2, 2002.

88. C. Reichart, "Earlier onset of bipolar disorder in children by antidepressants or

stimulants," Journal of Affective Disorders 78 (2004): 81-84. Also see abstracts

presented at the Fourth International Conference on Bipolar Disorder in Pittsburgh,

June 2001.

89. B. Geller, "Child and adolescent bipolar disorder," Journal of the American Acad¬

emy of Child & Adolescent Psychiatry 36 (1997): 1168-76.

90. Papolos, "Antidepressant-induced adverse effects."

91. G. Faedda, "Treatment-emergent mania in pediatric bipolar disorder," Journal of

Affective Disorders (82): 149-58.

92. R. Pedis, "Long-term implications of early onset in bipolar disorder," Biological

Psychiatry 55 (2004): 875-81.

93. B. Birmaher, "Course and outcome of bipolar spectrum disorder in children and

adolescents," Development and Psychopathology 18 (2006): 1023-35.

94. M. DelBello, "Twelve-month outcome of adolescents with bipolar disorder

following first hospitalization for a manic or mixed episode," American Journal of

Psychiatry 164 (2007): 582-90.

95. T. Goldstein, "Psychosocial functioning among bipolar youth," Journal of Affective

Disorders 114 (2009): 174-83.

96. B. Geller, "Two-year prospective follow-up of children with a prepubertal and early

adolescent bipolar disorder phenotype," American Journal of Psychiatry 159

(2002): 927-33.

97. "Hayes says new treatments for pediatric bipolar disorder not ready for prime time"

(December 3, 2008 press release), accessed at hayesinc.com, August 2, 2009.

98. Social Security Administration, annual statistical reports on the SSI program, 1996-

2008; Social Security Bulletin, Annual Statistical Supplement, 1988-1992.

99. Pediatric Academic Societies, "Pediatric psychiatry admissions on the rise," May 16,

2000, press release.

100. D. Satcher, Report of Surgeon General's Conference on Children's Mental Health

(U.S. Dept, of Health and Human Services, 2001).

101. B. Whitford, "Depression, eating disorders and other mental illnesses are on the

rise," Newsweek, August 27, 2008.

102. U.S. Government Accountability Office, "Young adults with serious mental illness"

(June 2008).

Chapter 12: Suffer the Children

1. J. Zito, "Psychotropic medication patterns among youth in foster care," Pediatrics

121 (2008): 157-63.

NOTES

385

Chapter 13: The Rise of an Ideology

1. C. Ross, Pseudoscience in Psychiatry (New York: John Wiley & Sons, 1995).

2. G. Klerman, "A debate on DSM-III," American journal of Psychiatry 141 (1984):

539-42.

3. M. Sabshin, "Report of the medical director," American journal of Psychiatry 137

(1980): 1308.

4. See blurbs for second edition of The Myth of Mental Illness, published by Harper &c

Row in 1974.

5. B. Nelson, "Psychiatry's anxious years," New York Times, November 2, 1982.

6. D. Adler, "The medical model and psychiatry's tasks," Hospital and Community

Psychiatry 32 (1981): 387-92.

7. Sabshin, "Report of the medical director."

8. Nelson, "Psychiatry's anxious years."

9. Copy from a Smith Kline and French advertisement that ran monthly in Mental

Hospitals in 1962.

10. L. Thorne, "Inside Russia's psychiatric jails," New York Times Magazine, June 12,

1977.

11. U.S. Senate, Committee on the Judiciary, Subcommittee to Investigate Juvenile

Delinquency, Drugs in Institutions, 94th Cong., 1st sess., 1975.

12. A. Tone, The Age of Anxiety (New York: Basic Books, 2009), 176.

13. M. Smith, Small Comfort (New York: Praeger, 1985), 32.

14. Interview with Arthur Piatt, June 8, 2009.

15. M. Sabshin, "On remedicalization and holism in psychiatry," Psychosomatics 18

(1977): 7-8.

16. A. Ludwig, "The medical basis of psychiatry," American journal of Psychiatry 134

(1977): 1087-92.

17. P. Blaney, "Implications of the medical model and its alternatives," American Jour¬

nal of Psychiatry 132 (1975): 911-14.

18. S. Guze, "Nature of psychiatric illness," Comprehensive Psychiatry 19 (1978):

295-307.

19. Adler, "The medical model."

20. M. Wilson, "DSM-III and the transformation of American psychiatry," American

journal of Psychiatry 150 (1993): 399-410.

21. S. Kirk, The Selling ofDSM (New York: Aldine de Gruyter, 1992), 114.

22. Ibid, 134.

23. M. Sabshin, "Turning points in twentieth-century American psychiatry," American

Journal of Psychiatry (1990): 1267-74.

24. Klerman, "A debate on DSM-III."

25. J. Maxmen, The New Psychiatrists (New York: New American Library, 1985),

35,31.

26. H. Kutchins, Making Us Crazy (New York: The Free Press, 1997), 248.

27. Kirk, The Selling ofDSM, 115.

28. M. Sabshin, "Report of the medical director" (1980), 1308.

386

NOTES

29. L. Havens, "Twentieth-century psychiatry," American journal of Psychiatry 138

(1981): 1279-87.

30. B. Bursten, "Rallying 'round the medical model," Hospital and Community Psychi¬

atry 32(1981): 371.

31. Sources for this political battle include reviews by NIMH's "Clinical Programs Proj¬

ects Research Review Committee" on April 27, 1970; April 1-2, 1973; April 1974;

April 21, 1975; June 27, 1977; December 1, 1977; February 17-18, 1978; and June

26-27, 1978.

32. Interview with Loren Mosher, December 1, 2000.

33. M. Sabshin, "Report of the medical director," American Journal of Psychiatry 138

(1981): 1418-21.

34. P. Breggin, Toxic Psychiatry (New York: St. Martin's Press, 1991), 360.

35. Sabshin, "Report of the medical director" (1981).

36. M. Sabshin, "Report of the medical director," American Journal of Psychiatry 140

(1983): 1398-1403.

37. R. Peele, "Report of the speaker-elect," American Journal of Psychiatry 143 (1986):

1348-50.

38. M. Sabshin, "Report of the medical director," American Journal of Psychiatry 143

(1986): 1342-46.

39. M. Sabshin, "Report of the medical director," American Journal of Psychiatry 145

(1988): 1338 A 12.

40. Sabshin, "Report of the medical director" (1981).

41. M. Sabshin, Changing American Psychiatry (Washington, DC: American Psychiatric

Publishing, Inc., 2008), 78.

42. Sabshin, "Report of the medical director" (1983).

43. Sabshin, "Report of the medical director" (1986).

44. New York Times , November 26, 1981; September 7, 1982; July 29, 1984.

45. J. Franklin, "The Mind-Fixers," Baltimore Evening Sun, July 1984.

46. M. Gold, The Good News About Depression (New York: Villard Books, 1987),

xi-xiii.

47. N. Andreasen, The Broken Brain (New York: Harper & Row, 1984), 29-30.

48. Ibid, 138.

49. Franklin, "The Mind-Fixers."

50. Sabshin, Changing American Psychiatry, 194.

51. M. Dumont, "In bed together at the market," American Journal of Orthopsychiatry

60 (1990): 484-85.

52. F. Gottlieb, "Report of the speaker," American Journal of Psychiatry 142 (1985):

1246-49.

53. Breggin, Toxic Psychiatry, 46, 357.

54. P. Breggin, Medication Madness (New York: St. Martin's Press, 2008), 150.

55. S. Boseley, "Scandal of scientists who take money for papers ghostwritten by drug

companies," Guardian, February 7, 2002.

56. M. Angel, "Is academic medicine for sale?" New England Journal of Medicine 342

(2000): 1516-18.

NOTES

387

57. D. Regier, "The NIMH depression awareness, recognition, and treatment pro¬

gram," American Journal of Psychiatry 145 (1988): 1351-57.

58. Breggin, Toxic Psychiatry, 14.

59. E. Foulks, "Advocating for persons who are mentally ill," Administration and

Policy in Mental Health and Mental Health Services Research 27 (2000): 353-67.

60. A. Hatfield, "The National Alliance for the Mentally 111," Community Mental

Health Journal 27 (1991): 95-103.

61. E. Benedek, "Report of the secretary," American Journal of Psychiatry 144 (1987):

1381-88.

62. Breggin, Toxic Psychiatry, 363.

63. Foulks, "Advocating for persons."

64. K. Silverstein, " Prozac.org ," Mother Jones, November/December 1999.

65. R. Behar, "The thriving cult of greed and power," Time, May 6, 1991.

Chapter 14: The Story That Was... and Wasn't Told

1. D. Healy, Mania (Baltimore: Johns Hopkins University Press, 2008), 132.

2. G. Carson, The Roguish World of Doctor Brinkley (New York: Rinehart & Co.,

1960).

3. P. Breggin, Brain-Disabling Treatments in Psychiatry (New York: Springer Publish¬

ing Co., 2008), 390.

4. "Fluoxetine project team meeting," July 31, 1978, accessed at healyprozac.com .

5. "Fluoxetine project team meeting," July 23, 1979, accessed at healyprozac.com .

6. J. Cornwell, The Power to Harm (New York: Viking, 1996), 147-48.

7. D. Healy, Let Them Eat Prozac (New York: New York University Press, 2004), 39.

8. Ibid, 128.

9. Ibid, 249.

10. BGA letter to Eli Lilly, May 25, 1984, Forsyth v. Eli Lilly trial documents, exhibit

42. See baumhedlundlaw.com/media/timeline .

11. Forsyth v. Eli Lilly trial documents, exhibit 58.

12. Cornwell, The Power to Harm, 198.

13. Healy, Let Them Eat Prozac, 35.

14. P. Breggin, Talking Back to Prozac (New York: St. Martin's Press, 1994), 41.

15. Ibid, 46.

16. Ibid, 90. Also see P. Breggin, Brain-Disabling Treatments in Psychiatry, 79,

86,91.

17. D. Graham, "Sponsor's ADR submission on fluoxetine dated July 17, 1990," FDA

document, September 1990.

18. T. Moore, "Hard to Swallow," Washingtonian, December 1997.

19. D. Kessler, "Introducing MEDWatch," Journal of the American Medical Association

269(1993): 2765-68.

20. J. Bremner, "Fluoxetine in depressed patients," Journal of Clinical Psychiatry 45

(1984): 414-19.

21. J. Feigner, "A comparative trial of fluoxetine and amitriptyline in patients with

major depressive disorder," Journal of Clinical Psychiatry 46 (1985): 369-72.

388

NOTES

22. J. Cohn, "A comparison of fluoxetine, imipramine, and placebo in patients with

major depressive disorder," Journal of Clinical Psychiatry 46 (1985): 26-31.

23. J. Wernicke, "The side effect profile and safety of fluoxetine," Journal of Clinical

Psychiatry 46 (1985): 59-67.

24. P. Stark, "A review of multicenter controlled studies of fluoxetine vs. imipramine

and placebo in outpatients with major depressive disorder," Journal of Clinical Psy¬

chiatry 46 (1985): 53-58.

25. S. Levine, "A comparative trial of a new antidepressant, fluoxetine," British Journal

of Psychiatry 150 (1987): 653-55.

26. R. Pary, "Fluoxetine: prescribing guidelines for the newest antidepressant," South¬

ern Medical Journal 82 (1989): 1005-9.

27. D. Regier, "The NIMH depression awareness, recognition and treatment program,"

American Journal of Psychiatry 145 (1988): 1351-57.

28. Healy, Let Them Eat Prozac, 9.

29. F. Schumer, "Bye-Bye, Blues," New York, December 18, 1989.

30. G. Cowley, "Prozac: A Breakthrough Drug for Depression," Newsweek, March 26,

1990.

31. N. Angier, "New antidepressant is acclaimed but not perfect," New York Times,

March 29, 1990.

32. B. Duncan, "Exposing the mythmakers," Psychotherapy Networker, March/April

2000 .

33. M. Waldholz, "Prozac said to spur idea of suicide," Wall Street Journal, July 18,

1990.

34. Ibid. Also see S. Shellenbarger, "Eli Lilly stock plunges $4,375 on news of another

lawsuit over Prozac drug," Wall Street Journal, July 27, 1990.

35. Memo from Leigh Thompson to Allan Weinstein, February 7, 1990, accessed at

healyprozac.com

36. Memo from Mitch Daniels to Leigh Thompson, "Upcoming TV appearance," April

15, 1991, accessed at healyprozac.com .

37. Ibid.

38. T. Burton, "Medical flap: Anti-depression drug of Eli Lilly loses sales after attack by

sect," Wall Street Journal, April 19, 1991.

39. L. Garnett, "Prozac revisited," Boston Globe, May 7, 2000.

40. R. Behar, "The Thriving Cult of Greed and Power," Time, May 6, 1991.

41. T. Burton, "Panel finds no credible evidence to tie Prozac to suicides and violent be¬

havior," Wall Street Journal, September 23, 1991.

42. S. Begley, "Beyond Prozac," Newsweek, February 7, 1994.

43. P. Breggin, Toxic Psychiatry (New York: St. Martin's Press, 1991), 348-50. In this

book, Breggin detailed the bad science involved in the Xanax trials, the co-opting of

academic psychiatry, and the involvement of the APA in marketing the drug.

44. "High Anxiety," Consumer Reports, January 1993.

45. C. Ballenger, "Alprazolam in panic disorder and agoraphobia," Archives of General

Psychiatry 45 (1988): 413-22.

NOTES

389

46. R. Noyes, "Alprazolam in panic disorder and agoraphobia," Archives of General

Psychiatry 45 (1988): 423-28.

47. J. Pecknold, "Alprazolam in panic disorder and agoraphobia," Archives of General

Psychiatry 45 (1988): 429-36.

48. Ballenger, "Alprazolam in panic disorder."

49. Noyes, "Alprazolam in panic disorder."

50. Pecknold, "Alprazolam in panic disorder."

51. I. Marks, "The 'efficacy' of alprazolam in panic disorder and agoraphobia,"

Archives of General Psychiatry 46 (1989): 668-72.

52. I. Marks, "Reply to comment on the London/Toronto study," British Journal of Psy¬

chiatry 162 (1993): 790-94.

53. Breggin, Toxic Psychiatry, 344-53.

54. F. Pollner, "Don't overlook panic disorder," Medical World News, October 1, 1991.

55. J. Randal, "In a panic?" St. Louis Post-Dispatch, October 7, 1990.

56. H. Brown, "Panic attacks keeps thousands from malls, off roads," Associated Press,

November 19, 1990.

57. R. Davis, "When panic is disabling," Chicago Sun-Times, June 29, 1992.

58. "High Anxiety," Consumer Reports.

59. FDA reviews of risperidone data included the following written commentaries:

reviews by Andrew Mosholder, May 11, 1993, and November 7, 1993; David

Hoberman, April 20, 1993; and Thomas Laughren, December 20, 1993.

60. Approval letter from Robert Temple to Janssen Research Foundation, December 29,

1993.

61. S. Marder, "The effects of risperidone on the five dimensions of schizophrenia

derived by factor analysis," Journal of Clinical Psychiatry 58 (1997): 538-46.

62. "New hope for schizophrenia," Washington Post, February 16, 1993.

63. "Seeking safer treatments for schizophrenia," New York Times, January 15, 1992.

64. FDA reviews of olanzapine data included the following written commentaries:

reviews by Thomas Laughren on September 27, 1996; by Paul Andreason on July

29 and September 26, 1996; and by Paul Leber on August 18 and August 30,

1996.

65. C. Beasley, "Efficacy of olanzapine," Journal of Clinical Psychiatry 58, suppl. 10

(1997): 7-12.

66. "Psychosis drug from Eli Lilly racks up gains," Wall Street Journal, April 14, 1998.

67. "A new drug for schizophrenia wins approval from the FDA," New York Times,

October 2, 1996.

68. "Schizophrenia, close-up of the troubled brain," Parade, November 21, 1999.

69. "Mental illness aid," Chicago Tribune, June 4, 1999.

70. "Lives recovered," Los Angeles Times, January 30, 1996.

71. P. Weiden, Breakthroughs in Antipsychotic Medications (New York: WW Norton,

1999), 26

72. Wall Street Journal, "Psychosis drug from Eli Lilly."

73. "High Anxiety," Consumer Reports.

390

NOTES

74. J. Lieberman, "Effectiveness of antipsychotic drugs in patients with schizophrenia,"

New England Journal of Medicine (2005): 1209-33.

75. L. Davies, "Cost-effectiveness of first- v. second-generation antipsychotic drugs."

British Journal of Psychiatry 191 (2007): 14-22.

76. P. Tyrer, "The spurious advance of antipsychotic drug therapy," Lancet 373 (2009):

4-5.

77. Interview with Peter Breggin, October 10, 2008.

78. Healy interview on CBS News and Current AJfairs, June 12, 2001.

79. D. Healy, "Psychopharmacology and the government of the self," talk given

November 30, 2000, at the University of Toronto.

80. E-mail from David Goldbloom to David Healy, December 7, 2000.

81. Interview with Healy by e-mail, July 4, 2009.

82. Memo from Larry Carpman to Steve Kurkjian, April 11, 2000.

83. "Science News from 2007," NIMH website, accessed on July 2, 2009.

84. NIMH press release, July 20, 2007.

85. J. Sharkey, "Delusions; paranoia is universal," New York Times, August 2, 1998.

86. Search of NAMI website on July 7, 2009.

87. R. Hales, The American Psychiatric Publishing Textbook of Psychiatry (Arlington,

VA: American Psychiatric Publishing, 2008).

Chapter 15: Tallying Up the Profits

1. D. Carlat, "Dr. Drug Rep," New York Times, November 25, 2007.

2. NAMI IRS 990 Form, 2000.

3. B. Koerner, "First you market the disesase, then you push the pills to treat it,"

Guardian, July 30, 2002.

4. E. Tanouye, "Antidepressant makers study kids' market," Wall Street Journal, April

4, 1997.

5. B. Strauch, "Use of antidepression medicine for young patients has soared," New

York Times, August 10, 1997.

6. Tanouye, "Antidepressant makers."

7. Deposition of Joseph Biederman in legal case of Avila v. Johnson & Johnson Co.,

February 26, 2009, pages 139, 231, 232, 237.

8. J. Biederman, "Attention-deficit hyperactivity disorder and juvenile mania," Journal

of the American Academy of Child & Adolescent Psychiatry 35 (1996): 997-1008.

9. Deposition of Joseph Biederman, p. 158.

10. Margaret Williams, report on a sales call. May 17, 2002.

11. J. J. Zorc, "Expenditures for psychotropic medications in the United States in

1985," American Journal of Psychiatry 148 (1991): 644-47

12. "Top therapeutic classes by U.S. sales, 2008," IMS Health.

13. S. Giled, "Better but not best," Health Affairs 28 (2009): 637-48.

14. These calculations are based on Eli Lilly's annual 10-K reports filed with the SEC

from 1987 to 2000. Capitalization figures for 1987 and 2000 are based on prices in

the fourth quarter of each year.

15. J. Pereira, "Emory professor steps down," Wall Street Journal, December 23, 2008.

NOTES

391

16. C. Schneider, "Emory psychiatrist reprimanded over outside work," Atlanta

Journal-Constitution, June 11, 2009.

17. G. Harris, "Radio host has drug company ties," New York Times, November 22,

2008.

18. GlaxoSmithKline internal memo, "Seroxat/Paxil adolescent depression. Position

piece on the phase III studies," October 1998.

19. M. Keller, "Efficacy of paroxetine in the treatment of adolescent major depression,"

Journal of the American Academy of Child & Adolescent Psychiatry 40 (2001):

762-72.

20. E. Ramshaw, "Senator questions doctors' ties to drug companies," Dallas Morning

News, September 24, 2008.

21. L. Kowalczyk, "US cites Boston psychiatrist in case vs. drug firm," Boston Globe,

March 6, 2009.

22. G. Harris, "Lawmaker calls for registry of drug firms paying doctors," New York

Times, August 4, 2007.

23. G. Harris, "Researchers fail to reveal full drug pay," New York Times, June 8, 2008.

24. Avila v. Johnson & Johnson, deposition of Joseph Biederman, February 26, 2009,

119.

25. J. Biederman, Annual Report 2002: The Johnson & Johnson Center for Pediatric

Psychopathology at the Massachusetts General Hospital.

26. J. Olson, "Drug makers step up giving to Minnesota psychiatrists," Pioneer Press,

August 27, 2007.

27. Margaret Williams, reports on sales calls, April 20, 2001, and April 8, 2002.

28. Eli Lilly grant registry, 2009, 1st quarter.

29. E. Mundell, "U.S. spending on mental health care soaring," HealthDay, August 6,

2009.

30. T. Mark, "Mental health treatment expenditure trends, 1986-2003," Psychiatric

Services 58 (2007): 1041-48. Seven percent of national health expenditures in 2008

went to mental health services; by 2015, this figure is expected to rise to 8 percent.

Data on national health expenditures in 2008, and projected expenditures in 2015,

are from the U.S. Department of Health and Human Services.

Chapter 16: Blueprints for Reform

1. MindFreedom, "Original statement by the fast for freedom in mental health," July

28, 2003.

2. Letter from James Scully to David Oaks, August 12, 2003.

3. Letter from MindFreedom scientific panel to James Scully, August 22, 2003.

4. APA statement on "diagnosis and treatment of mental disorders," September 26,

2003.

5. Letter from MindFreedom scientific panel to James Scully, December 15, 2003.

6. Interview with David Oaks, October 4, 2009.

7. J. Modrow, How to Become a Schizophrenic (Seattle: Apollyon Press, 1992), ix.

8. Interview with David Healy in Bangor, Wales, September 4, 2009.

9. D. Healy, "Psychiatric bed utilization," Psychological Medicine 31 (2001): 779-90;

392

NOTES

D. Healy, "Service utilization in 1896 and 1996," History of Psychiatry 16 (2005):

37-41. Also, Healy, unpublished data on readmission rates for first-episode psy¬

chosis, 1875-1924, and 1994-2003.

10. Interviews with Yrjo Alanen, Jukka Aaltonen, and Viljo Rakkolainen in Turku,

Finland, September 7, 2009.

11. V. Lehtinen, "Two-year outcome in first-episode psychosis treated according to an

integrated model," European Psychiatry 15 (2000): 312-20.

12. Interview with Jaakko Seikkula in Jyvaskyla, Finland, September 9, 2009.

13. J. Seikkula, "Five year experience of first-episode nonaffective psychosis in open-

dialogue approach," Psychotherapy Research 16 (2006): 214-28. Also see:

J. Seikkula, "A two-year follow-up on open dialogue treatment in first episode psy¬

chosis," Society of Clinical Psychology 10 (2000): 20-29; J. Seikkula, "Open dia¬

logue, good and poor outcome," Journal of Constructivist Psychology 14 (2002):

267-86; J. Seikkula, "Open dialogue approach: treatment principles and prelimi¬

nary results of a two-year follow-up on first episode schizophrenia," Ethical Human

Sciences Services 5 (2003): 163-82.

14. Interviews with staff at Keropudas Hospital in Tornio, Finland, September 10 and

11,2009.

15. Outcomes for 2002-2006 study and for spending in western Lapland on psychiatric

services from interviews with Jaakko Seikkula and Birgitta Alakare. See also the

published papers by Seikkula, op. cit.

16. J. Cullberg, "Integrating intensive psychosocial therapy and low dose medical treat¬

ment in a total material of first episode psychotic patients compared to treatment as

usual," Medical Archives 53 (1999): 167-70.

17. W. Buchan, Domestic Medicine (Boston: Otis, Broaders, and Co., 1846), 307.

18. National Institute for Health and Clinical Excellence, "Depression," December

2004.

19. Interview with Andrew McCulloch in London, September 3, 2009.

20. F. Dimeo, "Benefits from aerobic exercise in patients with major depression," British

Journal of Sports Medicine 35 (2001): 114-17; K. Knubben, "A randomized, con¬

trolled study on the effects of a short-term endurance training programme in pa¬

tients with major depression," British Journal of Sports Medicine 41 (2007): 29-33;

A. Strohle, "Physical activity, exercise, depression and anxiety disorders," Journal of

Neural Transmission 116 (2009): 777-84.

21. J. Blumenthal, "Effects of exercise training on older patients with major depres¬

sion," Archives of Internal Medicine 159 (1999): 2349-56.

22. Ibid.

23. Interviews with Tony Stanton and staff at Seneca Center in San Leandro, California,

July 13 and 14, 2009.

24. Interviews with Keith Scott and Chris Gordon, Framingham, Massachusetts,

October 1, 2009.

25. Ibid.

26. Interview with Jim Gottstein in Anchorage, Alaska, May 10, 2009.

NOTES

393

27. M. Ford, "The psychiatrist's double bind/' American Journal of Psychiatry 137

(1980): 332-39.

28. Myers v. Alaska Psychiatric Institute, Alaska Supreme Court No. S-11021.

29. Interview with Susan Musante in Anchorage, Alaska, May 10, 2009.

Epilogue

1. E. Whipple, Character and Characteristic Men (Boston: Ticknor & Fields, 1866), 1.

ACKNOWLEDGMENTS

As I began reporting this book, I reached out to leaders of various

"consumer" groups for help in locating "patients" to interview. I

wanted to find people with different diagnoses and of various ages,

and before long I had a list of more than 100 people willing to tell

me their stories. I am deeply grateful to all those who helped me

find patients to interview, and to all of those who spoke to me about

their lives. In addition to those named in the book, I want to thank

the following people: Camille Santoro, Jim Rye, Sara Sternberg,

Monica Cassani, Brenda Davis, Lauren Tenney, Cheryl Stevens,

Ellen Liversidge, Howard Trachtman, Jennifer Kinzie, Kathryn Cas-

cio, Shauna Reynolds, Maggie McClure, Renee LaPlume, Chaya

Grossberg, Lyle Murphy, Oryx Cohen, Will Hall, Evelyn Kaufman,

Dianne Dragon, Melissa Parker, Amanda Green, Nicki Glasser, Stan

Cavers, Cindy Votto, Eva Dech, Dennis Whetsel, Diana Petrakos,

Bert Coffman, Janice Sorensen, Joe Carson, Rich Winkel, Pat Risser,

Susan Hoffman, Les Cook, Amy Philo, Benjamin Bassett, Antti Sep-

pala, Chris LaBrusciano, Kermit Cole, David Oaks, Darby Penney,

and Michael Gilbert.

At every turn, the people I interviewed were extraordinarily

gracious with their time. In Syracuse, Gwen Oates, Sean Oates,

396

ACKNOWLEDGMENTS

Jason Smith, and Kelley Smith welcomed me into their homes. In

California, Tony Stanton organized two days of interviews with ad¬

ministrators, staff, and children at the Seneca Center. Throughout

this project, David Healy answered my inquiries, and when I inter¬

viewed him in North Wales, he and his wife, Helen, proved to be

gracious hosts. The architects of Open Dialogue therapy in Finland

collectively spent a week with me. I'm deeply indebted to Yrjo Ala-

nen, Jaakko Seikkula, and Birgitta Alakare for making my trip there

possible, and to Tapio Salo and his family for a wonderful evening

of conversation in Tornio.

As I worked on this book, I regularly drew sustenance from

friends and family. Thanks to Jang-Ho Cha, I was able to attend a

brain-cutting seminar at Massachusetts General Hospital. Matt

Miller, an associate professor at the Harvard School of Public

Health, proved to be an invaluable sounding board for thinking

about how medical therapies are evaluated and assessed. Cynthia

Frawley, my next-door office "neighbor," drew the many charts that

grace the book. And thanks to Joe Layden, Winnie Yu, and Chris

Ringwald for our regular conversations about the ups and downs of

the writer's life.

This is my fourth book, and I am now more convinced than ever

that writing a book —from the moment of first conception to the

day of publication —is best described as a collective enterprise. My

agent, Theresa Park, helped me shape the proposal and provided me

with invaluable guidance as I worked on the project. My editor,

Sean Desmond, pushed me to broaden the book's scope and its nar¬

rative arc, and when it came time to edit the manuscript, he im¬

proved it in innumerable ways. Every writer should be so lucky to

have an agent as supportive as Theresa Park and an editor as tal¬

ented as Sean Desmond. I am also indebted to Rick Willett for his

skillful copyediting; to Laura Duffy for her eye-catching cover; to

SongHee Kim for her wonderful layout; to Stephanie Chan for her

diligent management of the project; and to the many others at

Crown who contributed their talents to this book. And finally, I am

deeply grateful to Tina Constable for believing that the history told

in Anatomy of an Epidemic is one that deserves to be known.

INDEX

Page numbers of illustrations appear in

italics.

Aaltonen, Jukka, 337

Abbott Laboratories, 317

Ability (aripiprazole), 144-45, 212, 320n

acetylcholine, 61

Adderall (amphetamine), 252

Advocates, Inc., 214, 354

Age of Anxiety, The (Tone), 132

akathisia, 232, 249, 285, 301

Alakare, Birgitta, 341

Alanen, Yrjo, 337, 338, 339

Alaska Mental Health Assn., 355-57

Ambien (Zolpidem), 23

American Foundation for Suicide

Prevention, 327

American Medical Association, 39; drug

company alliances, 54-57

American Psychiatric Association (APA),

161-64, 168-69, 264; annual meeting,

4-5, 11, 115-18, 172-77; diagnostic

categories and market growth, 161-62,

168, 317; drug company alliances,

172-73, 273, 276-89, 278n, 298-99;

lithium approval and, 183; lobbying of

Congress, 277, 280; marketing of

antidepressants, 289-91; medical

(biological) model, 269-76, 304;

practice guide to depression, 180-81;

silencing of dissent, 304-7; Textbook of

Neuropsychiatry, 221; Textbook of

Psychiatry, 161, 225-26, 311-12;

Textbook of Psychopharmacology, 82,

322; Treatment of Psychiatric

Disorders, 272-73; wooing of media,

273-74

amitriptyline, 73, 74n

amphetamines, 64, 219, 228-29, 236. See

also Benzedrine; Ritalin

Andreasen, Nancy, 113-14, 275, 304, 332

Angier, Natalie, 291

anti-anxiety agents, 4, 51-53, 60, 65,

126-47; bipolar illness and, 142, 144,

148; disability numbers and, 146-47;

long-term effects, 136-38; side effects,

29, 140, 296-97; withdrawal from,

133-36, 134. See also benzodiazepine;

specific brand names

antibiotics, 41-42, 45, 51, 56, 57

antidepressants, 4, 60, 61, 62, 70, 73,

79-82, 148-71; bipolar disorder and,

175-77, 180, 181, 186-96, 193, 195;

case studies, 24-26, 148-50, 171,

196-204, 211-12; as cause of mental

illness, 26, 28, 30, 81-82, 157-60,

169-71, 197, 234; children given,

160-61, 229-32; disability numbers

and, 167-68, 168; hiding the evidence,

308-9, 312; marketing of, 74, 289-91 ;

nondrug outcomes vs. , 153-57,

164-69, 164n, 166, 166n, 167, 169,

185-96, 193, 195, 362; paradigm for

psychotropic drugs, 83-84; relapse risk

and, 158, 162, 169, 186; sales and use,

3, 320; side effects, 175-76, 191,

398 •

211-12; tricyclics, 153-55, 157, 158,

186, 198, 199, 229, 234, 240, 249,

285, 288 withdrawal psychosis, 250.

ANTi PSiKiYATRi TÜRKÇE KiTAP

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