THE ANATOMY OF AN EPIDEMIC
In this astonishing and startling book, award winning
science and history writer Robert Whitaker 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 disability 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 investigators 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
psychiatric medications through the prism of long-term results. Are long-term
recovery rates higher for medicated 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 of
Mental 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 literature, 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 ANATOMY OF AN EPIDEMIC
Magic Bullets, Psychiatric Drugs, and the Astonishing Rise
of Mental Illness in America
Robert Whitaker
CROW N PUBLISHER S
New York
To Lindsay
May you sing "Seasons of Love" again and be filled with joy
C O N T E N T S
Foreword ix
Part One: The Epidemic
A Modern Plague 3
Anecdotal Thoughts 12
Part Two: The Science of Psychiatric Drugs
The Roots of an Epidemic 39
Psychiatry's Magic Bullets 47
The Hunt for Chemical Imbalances 67
Part Three: Outcomes
A Paradox Revealed 89
. The Benzo Trap 126
An Episodic Illness Turns Chronic 148
The Bipolar Boom 172
An Epidemic Explained 200
The Epidemic Spreads to Children 216
Suffer the Children 247
Part Four: Explication of
a Delusion
The Rise of an Ideology 263
The Story That Was... and Wasn't Told 283
Tallying Up the Profits 313
Part Five: Solutions
Blueprints for Reform 331
Epilogue 361
Notes 363
Acknowledgments 395
Index 397
F O R E W O R D
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 companies, 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
patients in research settings. Even while I co-owned “Center
Watch”, 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
schizophrenia patients from their antipsychotic medications, which we figured
was an unethical thing to do. In fact, we thought it was outrageous.
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
researchers to have run dozens of withdrawal studies in which they carefully
tallied up the percentage of schizophrenia patients who became sick again and
had to be re-hospitalized. 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 research findings that just didn't
make sense. The first was by Harvard Medical School investigators, who in 1994
announced that outcomes for schizophrenia patients in the United States had
worsened during the past two decades and were now no better than they had been
a century earlier. The second was by the World Health Organization, 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 experts about the WHO findings, and they suggested that the
poor outcomes in the United States were due to social policies and cultural
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
antipsychotic 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 Organization
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 conventional
wisdom. I believed that psychiatric researchers were discovering 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
writing 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
I
A Modern Plague
'That is the essence of science: ask an impertinent
question, and you are on the way to
a pertinent answer."
— JACO B BRONOWSK I (1973) 1
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 85 0
adults and 25 0 children every day. And those startling 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.
Scientists are uncovering the biological causes of mental disorders, and
pharmaceutical companies have developed a number of effective medications 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 antidepressants 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
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 treatments 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
behavioral disorders that occur across the life span," Satcher wrote. The
introduction of Prozac and other "second-generation" psychiatric
drugs, the surgeon general added, was "stoked by advances in both
neurosciences and molecular biology" and represented yet another leap
forward in the treatment of mental disorders.3
Medical students training to be psychiatrists read about
this history in their textbooks, and the public reads about it in popular
accounts of the field. Thorazine, wrote University of Toronto professor Edward
Shorter, in his 1997 book, A History of Psychiatry, "initiated a
revolution in psychiatry, comparable to the introduction of penicillin in
general medicine."4 That was the start of the "psychopharmacology
era," and today we can rest assured that science 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, informed 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
understand this to be true. At the 161st annual meeting of the American
Psychiatric Association, which was held in May 200 8 in Washington, D.C.,
nearly half of the twenty thousand psychiatrists who attended were foreigners.
The hallways were filled with chatter about schizophrenia, bipolar illness,
depression, panic disorder, attention deficit/
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 knowledge 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 disabled 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 disorders, 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
exploration of science and history, and ultimately to a story with many
surprising twists. But this mystery arises from an in-depth
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 provide a rough count of the
number of people under governmental care because they have been disabled by
mental illness.
The Hospitalized Mentally III in 1955
|
First Admissions |
Resident Patients |
Psychotic Disorders |
|
|
Schizophrenia |
28.48,2 |
267.60 3 |
Manic-depressive |
9.679 |
50.93 7 |
Other |
1.387 |
14.73 4 |
Psychoneurosis (Anxiety) |
6.549 |
5.415 |
Personality Disorders |
8.730 |
9.73 9 |
All Others |
6.497 |
6.96 6 |
Although there were 558,922 resident patient s in state and
county menta l hospitals in 1955, only 355,000 suffered from menta l illness.
Th e other 200,000 were elderly patient s suffering from dementia, end-stage
syphilis, alcoholism, menta l retardation, and various neurological syndromes.
Source: Silverman, C. The Epidemiology of Depression (1968): 139.
In 1955, there were 566,00 0 people in state and county
mental hospitals. However, only 355,00 0 had a psychiatric diagnosis, as the
rest suffered from alcoholism, syphilis-related dementia, Alzheimer'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 46 8 Americans was
hospitalized due to a mental illness. In 1987, there were 1.25 million people
receiving an SSI or SSDI payment because they were disabled by mental illness,
or 1 in every 184 Americans.
Now it may be argued that this is an apples-to-oranges
comparison. 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 hospitalized in 195 5 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 195 5 were home to many
elderly schizophrenics. There were also many more mentally ill people who were
homeless and in jail in 198 7 than in 1955, and that population 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 disability rates between 1955 and 1987.
Fortunately, from 1987 forward it's an apples-to-apples
comparison, 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 second puzzle. In 1955, major depression and bipolar illness didn't
disable many people. There were only 50,93 7 people in state and county mental
hospitals with a diagnosis for one of those affective disorders.1 0 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 million people eighteen to sixty-four years old receiving a
federal payment because they are disabled by an affective disorder."
Moreover, this trend is accelerating: According to a 200 8 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 200 6 were diagnosed with an affective
illness (and another 8 percent were disabled by "anxiety disorder").
1 2
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 of the SSI an d SSD I numbers. Source: Social
Security Administration reports, 1987-2007.
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 disabled by a serious mental
illness. Such children comprised only 5. 5 percent of the 293,00 0 children on
the disability rolls—mental illness 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 561,56 9 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 disability in children, with
the mentally ill group comprising 50 percent 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 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 personally attest to how the drugs
have helped them lead normal lives. Furthermore, as Satcher noted in his 1999
report, the scientific literature 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 children 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 medications 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
exploration 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 disorders 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 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 200 8 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 benefits 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 understanding 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 imbalances" 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 constant 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
have to take psychiatric medications the rest of their
lives, just like a "diabetic takes insulin." That medical dictum
teaches all of the children 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
conventional history is true, and psychiatry has in fact made great progress in
identifying the biological causes of mental disorders and in developing
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 reasonable 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 200 8 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 disabling mental illness
what then? We will have documented a history 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.
2
Anecdotal Thoughts
"If we value the pursuit of knowledge, we must he free to follow wherever that search may lead us."
— ADLA I STEVENSO N (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 200 8 that I
came there, in order to attend a meeting of the Depression and Bipolar Support
Alliance, that sense of tranquility was heightened by the weather. It was one
of the most gorgeous nights of the summer, and as I approached 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 community, 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, Thursday, Friday, and
Saturday, and an evening meeting every Wednesday—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 that, in a small way, bore witness to the epidemic of disabling mental
illness that has erupted in our country over the past twenty years. The
Depression and Bipolar Support Alliance (DBSA) was founded in 198 5 (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 expected, 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 disorder 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
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 understanding to be helpful. The issue of
medication came up, and on this topic, opinions and experiences varied widely.
The former executive, 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 provided 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 atypical
[antipsychotics]. I'm hoping that will work."
After the group sessions ended, people gathered in the
cafeteria in clutches of two and three, sharing small talk. That made for a
pleasant 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
government'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 patient 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 disease are known as "case studies," and it is understood that
these anecdotal 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
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 immensely; 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
disabling 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 diagnosis 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 threatened, 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
remembers 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.
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 involved with a guy. I went to
a lot of parties and I couldn't concentrate 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 overalls
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 medication,"
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
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 antipsychotic 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 antipsychotics, Cathy clearly
responded very well to this new agent. She went back to school and earned a
degree in radio, film, and television 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 Risperdal, the very drug that has helped her so much,
nevertheless has proven to be a barrier to full-time work. Although she is
usually energetic 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. "Th e meds isolate you. They interfere with your
empathy. There is a flatness to you,
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 physically 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. "M y feet, my bladder, my heart, my
sinuses, the weight gain—I have it all." Even more alarming, in 200 6 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
believes that this drug is essential to her mental health today, and indeed,
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?
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 accomplished
in her life?
This is a question that Cathy, given her experience with
Risperdal, 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 productive 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:
"Th e 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 psychiatrists
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
thirteen-year-old son, Brandon, lives with him—"He is
on the football 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
amphetamines, marijuana, and cocaine, and I liked it. The drugs relaxed 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 conspiracies 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 diagnosed 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 hospitalizations, 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
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 schizophrenia, 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 Center, 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 himself, 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
institutionalized for decades. "Now I am on a ward with people urinating
on themselves," he recalls. "I' m 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
mentally 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 medication and spitting it out when the staff
weren't looking. "I could think again," he says. "Th e
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 symptoms,
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."
At first, it didn't go well. Like Madelyne, Brandon had been
born with health problems—he had an intestinal abnormality that required
surgery—and Tara broke down from that stress and was re-hospitalized. 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. "M y sister 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 success 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 schizophrenia 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
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 active 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,
Massachusetts, 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 conventional 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. Instead,
they soared beyond to what seemed a much better place. She now had energy to
burn. She took long runs and threw herself into 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 publishing 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
returned 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 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, Monica'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
apparently 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 someone so smart and accomplished end up
on that governmental program? 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?
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
"bipolar." She'd been so diagnosed in 1998, her psychiatrist
explaining that she suffered from a chemical imbalance in the brain, and by 200
2 she was on a cocktail of drugs that included an antipsychotic, Zyprexa. But
by the fall of 2008, she was off all psychiatric medications (and had been for
two years), she was thriving in a life that revolved 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
condominium 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 outbursts" 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
accomplished 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
justice—her father, a physician, volunteered half of his
time to work in a clinic he'd founded in Denver's tough "Five Points"
neighborhood—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 explanation 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 famous 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,
although 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
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
research; her previous work in a rug shop seemed about right. "That sounds
insane now," says Angela, who is a professor of mathematics 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
continued down that path except for the fact that in 200 3 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 withdrawal
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 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 permission 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 psychiatric 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 otherwise 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?
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 medication. 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 running
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
reluctant to diagnose him, and so they took him to a psychiatrist, who quickly
concluded that Nathan suffered from "attention deficit hyperactivity
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 medications. Nathan was put on a high dose of Ritalin, but "he
was like a 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 something in his hands, and he was put on Prozac
to control those symptoms. 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 diagnosed as suffering from both
bipolar and ADHD.
"They say that ADH D 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 afternoon, 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 medications 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.
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 answered. 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. "Jessica," 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 district 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 evaluation. There they saw a
nurse practitioner, who immediately concluded 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 antipsychotics," 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 Jessica 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
recommended. However, she couldn't find any study that told of good
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 behavior 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 as 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 another 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
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
antipsychotic, 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
3 The Roots of an Epidemic
"Americans have come to believe that science is capable of almost everything."
— D R. L O U I S M. O R R, A M A P R E S I D E N T (1958) 1
It may seem odd to begin an investigation of a modern-day
epidemic with a visit back to one of the great moments in medical history, but
if we are going to understand how our society came to believe that Thorazine
kicked off a psychopharmacological revolution, 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.
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 microbes 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 188 2 Congress of Internal Medicine in Germany. But Ehrlich's
studies 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 invading 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 bacteria 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 selectively 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 trypanosomes, 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
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 bestseller. "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 bullets against other disease-causing microbes, and although it took
twenty-five years, in 1935 Bayer chemical company provided medicine with its
second miracle drug. Bayer discovered that sulfanilamide, which was a
derivative of an old coal-tar compound, was fairly effective in eradicating
staphylococcal and streptococcal infections. 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 difficult to
culture, and even when they'd succeeded in growing it, they hadn't been able to
extract and purify sufficient quantities of the active 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, diphtheria, 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-
dieted those 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 1950 s began, medicine could look back and count
numerous other successes as well. Pharmaceutical firms had developed improved
anesthetics, sedatives, antihistamines, and anticonvulsants, evidence of how
scientists were getting better at synthesizing chemicals 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 provided doctors with an effective treatment for diabetes.
Although replacement 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 extraordinary 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 Andrew Carnegie
and John D. Rockefeller the most prominent benefactors, 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 leaders looked around for a medical field that had lagged behind, they
quickly found one that seemed to stand above all the rest. Psychiatry, 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
form the Association of Medical Superintendents of American
Institutions for the Insane. At that time, the asylums provided a form of
environmental care known as moral therapy, which had been introduced into the
United States by Quakers, and for a period, it produced 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 189 2 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 showers and prolonged baths, were said to be
helpful. An injection of extract 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 191 6 that he cured insanity by removing his patients' teeth. Fever
therapies were said to be beneficial, 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 1930 s and early 1940s, asylum psychiatrists
embraced a trio of therapies that acted directly on the brain, which the
popular 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 glucose, the New York Times explained, the
"short circuits of the brain
vanish, and the normal circuits are once more restored and bring
back with them sanity and reality."7 Next came the convulsive therapies.
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 public 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
comparison:
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 almost a physical existence of its own. I saw hundreds of patients living
under leaking roofs, surrounded by moldy, decaying walls, and sprawling on
rotting floors for want of seats or benches.9
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 address this problem,
which had remained hidden for so long. "Mental illness was the greatest
cause of noneffectiveness and loss of manpower that we met" during the
war, he said. 1 0
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 solutions 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 treatments, 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, forgetting 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
institutions 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
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 antibiotics, a rapidly growing
pharmaceutical industry ready to capitalize 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.
4 Psychiatry's Magic Bullets
"It was the first drug cure in all of psychiatric history."
— N A T H A N K L I N
E
DIRECTOR OF RESEARCH AT ROCKLAND
STATE HOSPITAL IN NEW YORK (1974) 1
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 invaders. 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.
Neuroleptics, Minor Tranquilizers, and Psychic Energizers
The story of the discovery of Thorazine, the drug that is
remembered today as having kicked off the psychopharmacology
"revolution," 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 phenothiazines 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 194 6
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 precipitous 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 discovered that in addition to its antihistaminic properties,
it induced a "euphoric quietude Patients
are calm and somnolent, with a relaxed and detached expression." 2
Promethazine, it seemed, might have use as an anesthetic. At
that time, barbiturates and morphine were regularly employed in medicine 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 functions," 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 anesthetic agents. A
cocktail that included promethazine—or an even more potent derivative of it, if
such a compound could be synthesized—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 456 0 RP into the rats:
Not only were the rats physically unable to climb the rope, they weren't
emotionally interested 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
surgical patients in June of 1951. As expected, it put them into a
"twilight state." Other surgeons tested it as well, reporting that it
served to "potentiate" the effects of the other anesthetic agents,
the cocktail 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.4
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 Portuguese neurologist, Egas
Moniz, who had invented it. The press, in its most breathless moments, had even
touted lobotomy as an operation 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 psychotic 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 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 reports 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 preoccupations, 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 treatment.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 nervous system.
Chlorpromazine, they concluded, induced deficits similar to those seen in
patients ill with encephalitis lethargica. "In fact," Deniker wrote,
"it would be possible to cause true encephalitis epidemics with the new
drugs. Symptoms progressed from reversible 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 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 introduction 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 quantities
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, urinary, and gastrointestinal illnesses. At that time,
there was a commercial disinfectant sold in Britain, called Phenoxetol, that
was advertised as effective against gram-negative bacteria in the environment,
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 surprise, 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 muscle paralysis—they
displayed this odd tranquility.
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 minutes of peace.
In 1947, Berger moved to the United States and went to work for Wallace
Laboratories in New Jersey, where he synthesized a compound, meprobamate, that
lasted eight times as long in the body as mephenesin. When Berger gave it to
animals, he discovered 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 0 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 nevertheless
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 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." 1 1
Psychiatry now had a new drug for quieting hospitalized
patients and a second one for easing anxiety, the latter a drug that could be
marketed 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 scientists
developed a novel compound, hydrazine, to serve as a substitute fuel. After the
war ended, chemical companies from the Allied countries swooped in to grab
samples of it, their pharmaceutical divisions 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, "patients 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. Tuberculosis patients treated with
iproniazid were also developing so many nasty side effects—dizziness, constipation,
difficulty urinating, 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 Hospital in
Orangeburg, New York, rescued iproniazid with a report that if depressed
patients were kept on the drug long enough, for at 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
revolution. 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 nervous 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 properly 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
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
organization 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 vendors of these products. Neither group needed to prove to a government
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 assessment. 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 advertisements 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 organization was
both providing a valuable service to the public and furthering 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 required 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 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
society. 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 prescription. "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 advertisements in its
journals for drugs that had not been approved by its Council on Pharmacy and
Chemistry. In 1955, the AMA abandoned 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 pharmaceutical industry, had "become what I would call
sissy," confessed 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.
* In
1914, the Harrison Narcotics Act required a doctor's prescription for opiates
and cocaine. The 1938 Food and Drug Cosmetics Act extended that
prescription-only requirement to a larger number of drugs.
The AMA and physicians were also now working with the 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 producing 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 articles 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." 1 7 In 1952, an industry trade publication, FDC Reports, noted
that the pharmaceutical 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." 1 8
This new marketplace for drugs proved profitable for all
involved. Drug industry revenues topped $1 billion in 1957, the pharmaceutical
companies enjoying earnings that made them "the darlings of Wall
Street," one writer observed. 19 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 advertisements 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 195 9 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 1950 s 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.
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 $350,00 0 developing Thorazine, having administered it to fewer than 150
psychiatric 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 imaginable. "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
difficult and costly, but it is a job our industry is privileged to
perform." 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 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
wonder 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 according to what
psychiatrists were telling newspaper and magazine reporters, it had amazing
properties.2 6 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." 27
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: Y E S, WE HAV E M I L T O W N ! The
comedian Milton Berle said that he liked the drug so much that he might change
his first name to Miltown. Wallace Laboratories hired Salvador Dali to help
stoke Miltown fever, paying the great artist $35,00 0 to create an exhibit at
an AM A convention that was meant to capture the magic of this new drug.
Attendees walked into a darkened claustrophobic tunnel that represented 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 makes them accessible to treatment." 2 9 Both
Thorazine and Miltown, explained the New York Times, should be considered as
"adjuncts to psychotherapy, not the cure." 3 0 Thorazine was called a
"major tranquilizer" and Miltown a "minor tranquilizer," and
when Hoffmann-La Roche brought iproniazid to market, it was described 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 "Th e 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 unbalanced cerebral
metabolism." 3 2 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 195 9 the New York Times called them
"antidepressants" for the first time. Both appeared to "reverse
psychic states," the paper said. 3 3 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." 3 4 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 curative 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." 35 Merck did the same,
marketing its drug Suavitil as "a mood normalizer.... Suavitil offers a
new and specific type of neurochemical treatment for the patient who is disabled
by anxiety, tension, depression, or obsessive-compulsive manifestations."
36
The final step in this image makeover of the psychiatric
drugs came in 1963. The NIMH had conducted a six-week trial of Thorazine and
other neuroleptics, and after these drugs were shown to be more effective than
a placebo in knocking down psychotic symptoms, the researchers concluded that
that the drugs should be regarded "as antischizophrenic in the broad
sense. In fact, it is questionable whether the term 'tranquilizer' should be
retained." 37
With this pronouncement by the NIMH, the transformation of
the psychiatric drugs was basically complete. In the beginning, Thorazine 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 developed for use in psychiatry because of their
"taming" properties were now "mood normalizers." The
psychic energizers were "antidepressants." All of these drugs were
apparently antidotes to specific disorders, and in that sense, they deserved to
be compared to antibiotics. They were disease-fighting agents, rather than mere
tonics. 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 understand 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
neurologists 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 debate that historian
Elliot Valenstein, in his book Blaming the Brain, characterized as the
"war between the sparks and the soups." However, by the mid-1950s,
researchers had isolated a number of possible 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 reserpine, an herbal drug used
in India to quiet psychotic patients, lowered brain levels of serotonin. It
also made the animals "lethargic" 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 discovered that if
animals were pretreated with iproniazid or imipramine 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 serotonin 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" neuron
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 metabolized by an enzyme and
shuttled off as waste, or else it flows back into the presynaptic neuron.
Researchers discovered that iproniazid thwarts the first process. It blocks an
enzyme, known as monoamine oxidase, that metabolizes norepinephrine and
serotonin. 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 norepinephrine are associated with behavioral
stimulation or excitement and generally exert an antidepressant effect in man.
From these findings a number of investigators have formulated 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 absolute 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
Parkinson's disease. In the late 1950s, Sweden's Arvid Carlsson and others
suggested that Parkinson's might be due to a deficiency in dopamine. 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 ganglia, 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. 40
Psychiatric researchers immediately understood the possible
relevance of this to schizophrenia. Thorazine and other neuroleptics regularly
induced Parkinsonian symptoms—the same tremors, tics, and slowed gait. And if
Parkinson's resulted from the death of dopaminergic neurons in the basal
ganglia, then it stood to reason those antipsychotic 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
"disconnected" certain brain regions. They weren't normalizing brain
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 neuroleptics 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 substantiated, it may have forgoing
consequences for the pathophysiology of schizophrenia. Overstimulation of
dopamine receptors could then be part of the etiology" 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
suffering 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" medication, with
total sales of such drugs reaching $69 2 million. 4 2
This was a narrative of a scientific triumph, and in the
late 1960 s 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
history of medicine itself."4 3 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."4 4 Anti-anxiety medicines, said
Frank Berger, the creator of Miltown, were "adding to happiness, human
achievement, and the dignity of man." 4 5 Such were the sentiments of
those who had led this revolution, and finally, at a 1970 symposium 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
understanding 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." 4 6
A Scientific Revolution... or a Societal Delusion?
Today, by retracing the discovery of the first generation of
psychiatric 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 expect 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.
Two possible histories were under way, and in the 1970 s and
1980s, researchers investigated the critical question: Do people diagnosed with
depression and schizophrenia suffer from a chemical imbalance that is then
corrected by the medication? Were the new drugs truly antidotes to something
chemically amiss in the brain?
5
The Hunt for Chemical Imbalances
The great tragedy of
science—the slaying of a beautiful hypothesis by an ugly fact."
— T H O M A S H U X L E Y (1870) 1
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 talents of the human mind. At the
invitation of a friend, Jang-Ho Cha, who is a neuroscientist at Massachusetts
General Hospital, I attended a brain-cutting seminar at the hospital, with the
thought that seeing a human brain would help me better visualize the
neurotransmitter 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
understood. 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
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 synaptic 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 telecommunications
cable, and once scientists discovered that dopamine, norepinephrine, and
serotonin fluoresced different colors when exposed 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 purposes, in regard to our
investigation of the chemical imbalance theory of mental disorders, we need to
look at that pathway in the brain for depression, and at the dopaminergic
pathway for schizophrenia.
The serotonergic pathway is one with ancient evolutionary
roots. Serotonergic neurons are found in the nervous systems of all vertebrates
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 system that is involved in the control of
respiratory, cardiac, and gastrointestinal activities. Other serotonergic
neurons have axons that ascend into all areas of the brain—the cerebellum, the
hypothalamus, the basal ganglia, the temporal lobes, the limbic system, the cerebral
cortex, and the frontal lobes. This pathway is involved in 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 either
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 reality. 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 synaptic gap, and thus the serotonergic pathways
in the brain were "underactive." Antidepressants brought serotonin levels
in the synaptic gap up to normal, and that allowed these pathways to transmit
messages at a proper pace. Meanwhile, the hallucinations and voices that
characterized schizophrenia resulted from overactive dopaminergic pathways.
Either the presynaptic neurons pumped out too much dopamine into the synapse or
the target neurons had an abnormally 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 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 cerebrospinal fluid for
these metabolites, and the amounts found would serve as an indirect gauge of
the synaptic levels of the neurotransmitters. 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 report 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 antidepressants), he announced that their
5-HIAA levels were lower than normal, but not "significantly" so. 3
Two years later, investigators at McGill University said that they, too, had
failed to find a "statistically significant" difference in the 5-HIAA
levels of depressed patients 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 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 scientific 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. Reserpine, Mendels and Frazer
concluded, didn't reliably induce depression 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 clinical
syndrome of depression," they wrote.7
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-HIAA levels, and these
low-serotonin patients were somewhat 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 disorder 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 "biological subgroup" of
depressed patients was mostly a story of wishful 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 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 depressed 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 investigators
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 theory 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 "biological
subgroup" of depressed patients with "low " levels of serotonin
were the best responders to an antidepressant, amitriptyline, that selectively
blocked its reuptake. If an antidepressant was an antidote 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." 1 0 Moreover, he and the other NIMH researchers
discovered—just as Asberg had—that 5-HIAA levels varied widely in depressed
patients. Some had high levels of serotonin metabolites in their cerebrospinal
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 evidence that any psychiatric disorder, including depression,
results from a deficiency of brain serotonin," said Stanford psychiatrist
David Burns in 2003. 1 1 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.12 In 2000, 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." 1 3 Yet, fueled by pharmaceutical
advertisements, the belief lived on, and it caused Irish psychiatrist David
Healy, who has written a number of books on the history of psychiatry, to quip
in 200 5 that this theory needed to be put into the medical dustbin, where
other such discredited theories can be found. "The serotonin theory of
depression," he wrote, with evident exasperation, "is comparable to
the masturbatory theory of insanity." 14
* The
NIMH researchers also looked at a number of other possible associations between
variable neurotransmitter levels and response to an antidepressant. 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 subgroups 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 serotonin, 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.
Dopamine Deja Vu
When Van Rossum set forth his dopamine hypothesis of
schizophrenia, 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 2. Next,
both investigators found that antipsychotics blocked 70 to 90 percent of the D2
receptors.1 5 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." 1 6
However, even as Snyder and Seeman were reporting their
results, 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 system." 1 7 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 different
from controls." 1 8 Autopsy studies also revealed that the brain tissue of
drug-free schizophrenics did not have abnormal levels of
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 overabundance 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 D2 receptors than normal. At first glance,
it seemed that the cause of schizophrenia had been found, but Seeman cautioned
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 increase in D2 receptors
might "have resulted from the long-term administration of
neuroleptics." 20
A variety of studies quickly proved that the drugs were
indeed the culprit. When rats were fed neuroleptics, their D2 receptors quickly
increased in number.2 1 If rats were given a drug that blocked D, receptors,
that receptor subtype increased in density.2 2 In each instance, 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 [D2 ] receptors were seen only in patients in whom
neuroleptic medication had been maintained until the time of death, indicating
that they were entirely iatrogenic [drug-caused]."2 3 A few years later,
German investigators reported the same results from their autopsy studies.2 4
Finally, investigators in France, Sweden, and Finland used positron emission
topography to study D,-receptor densities in living patients who had never been
exposed to neuroleptics, and all reported "no significant
differences" between the schizophrenics and "normal controls." 25
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 patients. 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 credibility for
psychiatrists," observed Pierre Deniker in 1990. 2 6 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 function in schizophrenia." 2 7 Still, the
public continued to be told that people diagnosed with schizophrenia had
overactive dopamine systems, with the drugs likened to "insulin for
diabetes," and thus former NIMH director Steve Hyman, in his 200 2 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. 28
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 imbalances, 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:
Researchers would identify the mechanism of action for a
class of drugs, how the drugs either lowered or raised levels of a brain
neurotransmitter, 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 hypothesis of depression had arisen out of "tunnel
thinking" that relied on an "inadequate evaluation of certain
findings not consistent with the initial assumption." 2 9 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 diminish certain phenomena of schizophrenia, but [the drugs] do
not pretend to be an etiological treatment of these psychoses." 3 0 The
chemical-imbalance theory of mental disorders, wrote David Healy, in his book
The Creation of Psychopharmacology, was embraced by psychiatrists because it
"set the stage" for them "to become real doctors." 3 1 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 reasons that will be explored later), and it has led those who have
investigated and written about this history to emphasize, time and again, the
same bottom-line conclusion. "The evidence does not support 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." 3 3 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." 3 4 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 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 1970 s and 1980s, investigators put together
detailed accounts 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 common process at work. But
since the story of chemical imbalances in the public mind really took off after
Eli Lilly brought Prozac (fluoxetine) 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, entering 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 serotonin 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 machine." If serotonin levels are too high,
they scream "turn it off." This is a feedback loop designed by
evolution to keep the serotonergic system in balance, and fluoxetine triggers
the latter message. With serotonin no longer being whisked away from the
synapse, the 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. 3 7 Other investigators subsequently
reported that "chronic fluoxetine treatment" may lead to a 50 percent
reduction in serotonin receptors in certain areas of the brain. 3 8 As a
result, the postsynaptic neurons become "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 "synaptic resilience."3 9 However, there is one other change
that occurs during 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
feedback 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 properties.
Psychiatrists had long observed that antidepressants took two or three weeks to
"work, " and thus the Eli Lilly researchers reasoned 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." 4 1 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.
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 neurotransmission," 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 system's feedback loop
is partially disabled. The postsynaptic neurons are "desensitized" to
serotonin. Mechanically speaking, the serotonergic 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 disrupted
serotonergic pathways, could be used to study "the role of serotonin
neurons in various brain functions—behavior, sleep, regulation of pituitary
hormone release, thermoregulation, pain responsiveness 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
hyperactivity" in rats and "suppressed RE M sleep" in both rats
and cats. 43
In 1991, in a paper published in the Journal of Clinical
Psychiatry, 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] environmental/biological
conditions. Thus, any behavioral or physiologic change produced under these
conditions might more appropriately be considered pathologic, rather than
reflective of the normal biological role of 5-HT [serotonin.]"44
During the 1970 s 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 D2 receptors in the brain. In
response, the presynaptic neurons begin pumping out more dopamine and the
postsynaptic neurons increase the density of their D2 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 pathways. 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 ofPsychopharmacology.45
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
D2 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."
A Paradigm for Understanding Psychotropic Drugs
Today, as provost of Harvard University, Steve Hyman is
mostly engaged 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 "Initiation and Adaptation: A Paradigm for
Understanding Psychotropic Drug Action," it was published in the American
Journal of Psychiatry, 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 adaptations. 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 receptors 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."
His was an elegant paper, and it summed up what had been
learned from decades of impressive scientific work. Forty years earlier, 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 detailed 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,
depression, 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 opening 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 diseases. Those
compounds were then found to cause alterations in mood, behavior, and thinking
that were seen as helpful to psychiatric patients. The drugs, in essence, were
perceived as having beneficial 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 produce
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 emotional response to environmental
stressors. Iproniazid was a "psychic stimulator," and if the report
of TB patients dancing in the
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, psychotropics 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
6 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."
— E M M A N U E L STIP, E U R O P E A N P S Y C H I A T R Y
( 2 O O 2 ) 1
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 1800 s 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 purchased 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 disorder. In the absence
of antipsychotic medications, how would peopie 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 population 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 illness, and that is an understanding that originated with the work of
German psychiatrist Emil Kraepelin. In the late 1800s, he systematically
tracked the outcomes of patients at an asylum in Estonia, and he observed that
there was an identifiable group that reliably deteriorated 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 189 9
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 199 0 article, "Is Schizophrenia What It Was? A Re-analysis of
Kraepelin's and Bleuler's Population," many of Kraepelin's dementia
praecox patients were undoubtedly suffering from a viral disease, encephalitis
lethargica, which in the late 1800 s had yet to be
identified. This disease caused people to turn delirious, or
to drop into a stupor, or to start walking in a jerky manner, and once Austrian
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 intellectually
deteriorated"—those types of schizophrenia patients, Boyle noted, largely
disappeared. As a result, the descriptions of schizophrenia in psychiatric
textbooks during the 1920 s and 1930 s 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
outcomes for that group of psychotic patients? Here, unfortunately, we run into
a second problem. From 190 0 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
concluded, with an air of satisfaction, that "segregation of the insane is
fairly complete." 3 As a result, many people diagnosed with schizophrenia
in the first half of the century were hospitalized and never discharged, but
that social policy was then misperceived as outcomes 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
embraced, 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
the community. Social policy changed and discharge rates
soared. As a result, there is a brief window of time, from 194 6 to 1954, when
we can look at how newly diagnosed schizophrenia patients fared and thereby get
a sense of the "natural outcomes" of schizophrenia 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 Hospital
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 21 6
schizophrenia patients admitted to Delaware 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 schizophrenia 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 1940 s and early 1950 s 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 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
function fairly well in the community.
*
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.
It is also important to note that the arrival of Thorazine
did not improve discharge rates in the 1950 s for people newly diagnosed with
schizophrenia, nor did its arrival trigger the release of chronic patients. In
1961, the California Department of Mental Hygiene reported 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 eighteen 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
1950 s that compared discharge rates for first-episode patients treated with
and without drugs, and the investigators concluded 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
mental hospitals—and thus the beginning of deinstitutionalization—got under way
in 1965 with the enactment of Medicare and Medicaid. In 1955, there were 267,00
0 schizophrenia patients in state and county mental hospitals, and eight years
later, this number had barely budged. There were still 253,00 0 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 noticeably drop, rather than in 1955, when Thorazine
was introduced. Unfortunately, our societal belief that it was this medication
that emptied the asylums, which is so central to the "psychopharmacology
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 195 6 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 changing. Equally problematic, what defined a "good
outcome"? Psychiatrists 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.1 1 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 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." 1 2
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
Psychopharmacology 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 settled 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 symptoms 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 medicine would prescribe an
antibiotic for a bacterial infection, a psychiatrist 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 provide any insight into
how patients were faring over the long term.
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
psychiatry's future. The use of the clinical trial would cause psychiatrists to
see their therapies through a very particular prism, and even at the 195 6
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 beginning of the scientific record that serves today as the "evidence
base" for these drugs. In the six-week trial, 27 0 patients were given
Thorazine or another neuroleptic (which were also known as "phenothiazines,")
while the remaining 74 were put on a placebo. The neuroleptics did help reduce
some target symptoms—unrealistic thinking, anxiety, suspiciousness, auditory hallucinations,
etc.—better than the placebo, and thus, according to the rating's scales
cumulative 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
at Harvard Medical School reviewed 149 such trials and found
that the antipsychotic drug proved superior to a placebo in 83 percent of them.
1 4 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.1 5 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
antipsychotic 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 chlorpromazine." 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.
a 200 2 article in the New England Journal of Medicine,
"Antipsychotic drugs are effective in treating acute psychotic symptoms
and preventing relapse." 1 7 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
effectiveness 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 treatment with conventional
antipsychotics is unclear." 18
This doubt prompted an extraordinary 2002 editorial in European
Psychiatry, penned by Emmanuel Stip, a professor of psychiatry at the
Universite de Montreal. "After fifty years of neuroleptics, are we able to
answer the following simple question: Are neuroleptics effective in treating
schizophrenia?" There was, he said, "no compelling evidence on the
matter, when 'long-term' is considered." 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
relapse studies dramatically increased the risk that the schizophrenia patients
would become sick again. Indeed, the relapse rate for gradually withdrawn
patients was similar to what it was for the drug-maintained patients.
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 treatment [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
suspicion. Schizophrenia patients discharged on medications were returning 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 researchers observed that "relapse is
greater in severity during drug administration than when no drugs are
given." 2 2 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: nausea, vomiting, diarrhea, agitation, insomnia, headaches,
and weird motor tics. 2 3 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.
These poor results prompted two psychiatrists at Boston
Psychopathic 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
antipsychotics, 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 194 7 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 196 7 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 psychotropic 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 1970 s 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
percent of the nonmedicated group relapsed within a year after discharge,
compared to 45 percent of the medicated group. The off-drug patients also
suffered less from depression, blunted emotions, 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 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 diagnosed 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 average, 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 "evidence 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/of f |
24 |
1.70 |
8 % |
Antipsychotic/of f |
17 |
2.79 |
47 % |
Placebo/o n |
17 |
3.54 |
53 % |
Antipsychotic/o n |
22 |
3.51 |
73 % |
In this
study, patients were grouped according to both their in-hospital care (placebo
or drug ) and whether they use d antipsychotics after they were discharged.
Thus, 24 of the 4 1 patients treated with placebo in the hospital remained off
the drugs during the follow-u p period. This never-exposed group had the best
outcomes by far. Rappaport, M. "Are there schizophrenic s for who m drugs
maybe unnecessary or contraindicated. " International Pharmaco-psychiatry
1 3 (1978): 100-11.
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 schizophrenics suffered from a
"broken brain." He believed that psychosis 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 hallucinations 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
healing 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." 2 7 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.
"Contrary to popular views, minimal use of
antipsychotic medications 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." 2 8
Three NIMH-funded studies, and all pointed to the same conclusion.
* Perhaps 50 percent of newly diagnosed schizophrenia patients, 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
psychiatry now faced:
There is no question that, once patients are placed on
medication, 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 antipsychotic medication may make some
schizophrenic patients 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
chronically ill.
---------------
* 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 without 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 successfully 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.
----------------
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 emotional "zombies." In 1972, researchers concluded that
neuroleptics "impaired learning." 3 0 Others reported that even if
medicated patients 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.3 1 None of this told of medicated schizophrenia
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 permanent 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 observed that
studies had shown that at least 50 percent of all schizophrenia patients could
fare well without the drugs. There was only one moral thing for psychiatry to
do: "Every schizophrenic outpatient maintained on antipsychotic medication
should have the benefit 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
withdrawn?" 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 explanation 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
percent of all D2 receptors in the brain. In an effort to compensate for this
blockade, the postsynaptic neurons increase the density of their D2 receptors
by 30 percent or more. The brain is now "supersensitive" to dopamine,
Chouinard and Jones explained, and this neurotransmitter is thought to be a
mediator of psychosis. "Neuroleptics can produce a dopamine supersensitivity
that leads to both dyskinetic and psychotic symptoms," they wrote.
"An implication is that the tendency toward psychotic relapse in a patient
who has developed such a supersensitivity is determined by more than just the
normal course of the illness." 34
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 transmission, and
in response the brain puts down the dopamine accelerator (the extra D2
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. 3 5
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 necessarily 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
withdrawal 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 neuroleptic 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,
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 prescribe higher doses of
antipsychotics to tamp down those tardive symptoms. "The most efficacious
treatment is the causative agent itself, 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
21 6 schizophrenia outpatients they studied showed signs of tardive psychosis.3
6 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 suffered 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." 3 7
Animal studies confirmed this picture too. Philip Seeman reported
that antipsychotics caused an increase in D2 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
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. Scientific 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 understand how the drugs acted on the brain, and once they began
investigating why patients were developing tardive dyskinesia and why they were
becoming so chronically ill, then this counterintuitive picture of the
drugs—that they were increasing the likelihood that patients 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? Psychiatry desperately needed
this discussion to go away. Soon the articles 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, assured 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 schizophrenia 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." 4 1
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 those 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 1950 s and early 1960s, Vermont State Hospital
discharged 26 9 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 relationships, were employed or otherwise productive citizens, were
able to care for themselves, and led full lives in general." 42 This was a
startling 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 "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 countries." They were
much more likely to be asymptomatic during the follow-up period, and even more
important, they enjoyed "an exceptionally good social outcome."
These findings stung the psychiatric community in the United
States and Europe, which protested that there must have been a design 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
results 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 maintained on antipsychotics, versus 61 percent of the
patients in the rich countries. Moreover, in Agra, India, where patients
arguably 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. 4 6 In this
cross-cultural study, the best outcomes were clearly associated with low
medication use. Later, in 1997, WHO researchers interviewed 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 "outcome differential" held up for "general
clinical state, symptomatology, disability, and social functioning." In
the developing countries, 53 percent of the schizophrenia patients were simply
"never psychotic" anymore, and 73 percent were employed.4 7 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 become dysfunctional. But there
are three dopaminergic pathways, and so it stands to reason that the third one,
which transmits messages to the frontal lobes, also becomes dysfunctional over
time. If so, researchers could expect to find a global decline in brain
function in patients diagnosed with tardive dyskinesia, and from 197 9 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 severe forms of the disorder are
most impaired cognitively."4 8 Researchers 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.4 9
Investigators have dubbed this long-term cognitive deterioration tardive dementia;
in 1994, researchers found that three-fourths of medicated 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
structures 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 reported that the drugs caused
basal ganglion structures and the thalamus to swell, and the frontal lobes to
shrink, with these changes in volumes "dose related." 5 1 Then, in
1998, Raquel Gur at the University of Pennsylvania Medical Center reported that
the swelling of the basal ganglia and thalamus was "associated with
greater severity 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 disengaged ("negative
symptoms"). The MR I 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
Seeman reported that all of these psychotic triggers cause
an increase in D2 receptors in the brain that have a "HIG H 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 mutations, drug abuse, or brain injury,
all of which may converge via D2 HIGH to elicit psychotic symptoms," he
wrote. 5 3
Seeman reasoned that this is why antipsychotics work: They
block D2 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" D2 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
Psychiatry 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 worsening of negative symptoms and functional impairment, and
thus Andreasen concluded that this shrinkage is evidence that schizophrenia is
a "progressive neurodevelopmental disorder," one which antipsychotics
unfortunately fail to arrest. "Th e 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
ineffective, rather than harmful, and two years later, she fleshed out this
picture. Her patients' cognitive abilities began to "worsen
significantly" five years after initial diagnosis, a decline tied to the
"progressive brain volume reductions after illness onset." 55 In
other words, as her patients' frontal lobes shrank in size, their ability to
think declined. But other researchers conducting MR I studies had found that
the shrinkage of the frontal lobes was drug-related, and in a 200 8 interview
with the New York Times, Andreasen conceded 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 activity. 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 psychiatrist Thomas McGlashan, who three decades
earlier had wondered whether antipsychotics were making patients "more
biologically vulnerable to psychosis," to once again question this entire
paradigm of care. He put his troubled thoughts into a scientific context:
In the short term, acute D2 [receptor] blockade detaches
salience and the patient's investment in positive symptoms. In the long term,
chronic D2 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 D2 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 200 6 issue of the Schizophrenia
Bulletin, and at that moment it seemed like the late 1970 s all over again. The
"cure," it seemed, had once again been proven to be "worse than
the disease."
The Clinician's Illusion
I attended the 200 8 meeting of the American Psychiatric
Association 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 197 5 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 periodically
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 investigation of the scientific literature to a fitting
climax. If the conventional wisdom is to be believed, then those who stayed on
antipsychotics should have had better outcomes. If the scientific literature 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
patients' fifteen-year outcomes in the Journal of Nervous and Mental Disease,
and he further updated that review in his presentation at the APA's 200 8
meeting.5 8 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 divergence 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 psychotic symptoms. In contrast, only 5 percent
of those taking anti-
Long-term Recovery Rates for Schizophrenia Patients
Source: Harrow, M. "Factor s involved in outcome
and recovery in schizophrenia patients not on antipsychotic medications. "
The Journal of Nervous and Mental Disease, 195 (2007): 406-14.
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 recovered, 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,
Spectrum of Outcomes in Schizophrenia Patients
The
spectrum of outcomes for medicat d versus unmedicated patients. Those on
antipsychotic s had a much lower recovery rate, and were mu h 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, 195 (2007):
406-14.
the most up-to-date one we have today. It also provides us
with insight into how long it takes for the better outcomes for nonmedicated
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 programs, they
stopped seeing therapists, they stopped telling people they had ever been
diagnosed with schizophrenia, and they disappeared 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
nonmedicated 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 stabilized on
the medications, this "better personhood" gave them the 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 [initially] who then went off
the medications." When I pressed on with a question about whether his
findings supported a different interpretation, 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. "Ou r data is overwhelming that not all schizophrenic 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
acknowledged, 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 antipsychotics 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 randomized studies conducted by Rappaport,
Carpenter, and Mosher; in the cross-cultural studies conducted by the World
Health Organization; and in the naturalistic studies conducted by Harding and
Harrow. 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
number 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 rehospitalized in follow-up periods of four and five years. This
was what we saw in Bockoven's study, too: Seventy-six percent of the psychotic
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 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 better than do those in the more modern era," said Maryland
psychiatrist 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
contributed to the rise in the number of disabled mentally ill. In 1955, there
were 267,00 0 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 disability rate of one in every 125 Americans.5 9
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 perceives 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
had been treated with some form of psychosocial care? Or if,
at some point early on, she had been encouraged to withdraw gradually 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 questions, 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 confused. "
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 medication. He is healthy today, he has
an evident zest for life, and he revels 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
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 interact
with my family members," she says, and that awkwardness followed 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 sophomore year she dropped out and went
to live with her mother in Boston, hoping to find a "purpose in
life." Instead, "my sense of reality 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 hospitalization, in February 1997, she was
diagnosed with schizophrenia, and this time she accepted the fact that she
would have to take antipsychotics 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 psychiatric 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 husband often cruelly taunted her,
telling her that she was "ugly" and had a "fat ass." She
chafed too over how everybody in the system treated her. "Recovery on the
med model requires you to be obedient, 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 formal 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 February 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. "No w 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 formal 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
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
hopefully 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 hospital."
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 dilated 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 physically 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—"I'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 responses to such stress
numbed by medication. "I'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 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 getting off meds does not mean that everyone can successfully
withdraw 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 200 5 when I decided to get better, that's
the dividing 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.' "
7
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 inretrospect it's difficult to put a
spanner into a wristwatch and expect that it won't do any harm."
— ALEC JENNER, BRITISH PHYSICIA N WHO CONDUCTE D FIRST
TRIALS OF A BENZODIAZEPIN E IN TH E UK (2003) 1
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.
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 physical 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.
Neurologists 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 nerve
doctor or a general practitioner for help. But if anxiety arose from a
psychological disorder in the brain, rather than from a frazzling of the
nerves, then it made sense that psychiatrists could tend to these patients, and
after Freud visited America in 1909, psychoanalytic societies began to form,
with New York City the hub of this new therapy. Nationwide, only 3 percent of
psychiatrists were in private practice in 1909 ; thirty years later, 38 percent
were seeing patients in private settings.2 Moreover, Freudian theory made
nearly everyone a candidate for the psychiatrist's couch.
"Neurotics," Freud explained during his 190 9 tour, "fall ill of
the same complexes with which we sound people struggle."3
Thanks to Freudian theories, psychiatric disorders were now
divided 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 patient in this way:
The chief characteristic of [neurotic] disorders is "anxiety,"
which may be directly felt and expressed or which may be unconsciously 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 reality
(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
5,41 5 "psychoneurotic" patients in state mental hospitals.5 As
Stanford psychiatrist Leo Hollister confessed after the benzodiazepines were
introduced, these drugs were "designed 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
future promised by Miltown inventor Frank Berger: "Tranquilizers,
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
published in medical journals that told—as two Harvard Medical School
researchers, David Greenblatt and Richard Shader, later recalled—of how it
"was almost magically effective in reducing anxiety." 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 literature 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 determine
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 Center in Lexington, Kentucky,
reported that it "could induce physical dependence in man." 9 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 symptoms like those of
narcotics users 'kicking the habit.' " 10
Publicly, the benzodiazepines mostly escaped this opprobrium
during the 1960s. When Hoffmann-La Roche brought Librium to market in 1960, it
claimed that its drug provided "pure anxiety relief," 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 insomnia, 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." 1 1 Although the FDA held a hearing on the matter, 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
demanded that they be classified as schedule IV drugs under the Controlled
Substances Act. This designation limited the number of refills a patient could
obtain without a new prescription, and revealed to the public that the
government had concluded that benzodiazepines were, in fact, addictive.
"Danger ahead! Valium—The Pill You Love Can Turn on
You," a Vogue headline screamed. A benzodiazepine, the magazine explained,
could lead to a "far worse addiction than heroin." 1 2 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. "M y withdrawal 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 accompanied my withdrawal." 1 3 The happiness pill of the
1950 s was turning 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." 1 4 Two
million Americans were said to be addicted to 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 Subcommittee
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." 1 6 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 recommended that "patients
receiving benzodiazepine therapy be carefully selected and monitored and that
prescriptions be limited to short- term use." 1 7 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 benzodiazepines never
really went away. Although the number of prescriptions 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.1 9 Psychiatrists continued
to prescribe benzodiazepines to many of their nervous patients, and in 2002,
Stephen Stahl, a well-known psychopharmacologist at the
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
Disorders." 2 0 Since that time, the prescribing of benzodiazepines in the
United States has increased, from 69 million prescriptions in 200 2 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 increase 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
rapidly, 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 somewhat mysteriously developed a fear of flying. But as
clinical trials revealed, 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 results could be said to
"hint at therapeutic efficacy," he wrote. 2 2 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 22 4 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 studies
would consistently show significant benzodiazepine therapeutic 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 functioning may be impaired,
and amnesia is a common effect of all benzodiazepines," they said. 2 4 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 benzodiazepines,
explained the importance of this finding in an interview: "Effectiveness
is a measure of what it's like in real practice." 2 6
Withdrawal syndromes
Although the first report of benzodiazepine dependence
appeared in the scientific literature in 1961, when Leo Hollister at Stanford
University reported that patients withdrawing from Librium were experiencing
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, reporting that when their patients stopped taking Valium, many
complained of "extreme anxiety." 2 7 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 anxiety.' " 2 8 In Britain,
Lader reported similar findings. "Anxiety rose sharply during withdrawal,
and to a point of panic in several patients. Patients commonly experienced
bodily symptoms of anxiety, such as a choking feeling, dry mouth, hot and cold,
legs like jelly, etc.
Rebound Anxiety with Valium
In
this 1985 study by British investigators, the patients treated with Valium did
not fare better than the placebo patients during the first six weeks. Th e
Valium patients were the n withdraw n from the drug and their anxiety symptom s
soared, to a much higher level than the symptom sin placebo patients. Source:
Power, K. "Controlled study of withdrawal symptom s an d rebound anxiety
after six week course of diazepam for generalised anxiety." British
Medical Journal 290 (1985): 1246-48.
Patients withdrawing from benzodiazepines, it seemed, were
becoming 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
vision, a ringing in the ears, extreme sensitivity to noise, a feeling that
insects were crawling over them, nightmares, hallucinations, extreme
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 is a severe illness," Ashton wrote. "The patients were
usually frightened, 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 benzodiazepine, 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 syndrome,"
their anxiety remaining at elevated levels "for many months after
benzodiazepine withdrawal," Ashton observed.3 1 Depression may deepen, and
the odd perceptual symptoms—the depersonalization, 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 neurotransmitter 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 activity. 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 neurotransmitter acts as the brain's brake on neuronal activity. A
benzodiazepine binds to the GABA receptor and, in so doing, amplifies GABA's
inhibitory effects. It pushes down on the GABA brake, so to speak, and as a
result, it suppresses central nervous system activity.
In response, the brain decreases its output of GABA and
decreases the density of its GABA receptors. It is trying to "restore
normal GABA transmission," British scientists explained in 1982. 3 2
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 withdrawal." " The anxiety, the insomnia, the sensation of
insects crawling 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. 3 4 Long-term benzodiazepine
use, she explained, may "give rise not only to slowly reversible
functional changes in the central nervous system, but may also occasionally
cause structural neuronal damage." 3 5 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
determined 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 supposed to treat? In 1991, Karl
Rickels at the University of Pennsylvania 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. 3 6
A few years later, he was back with a new study: When long-term users withdrew
from benzodiazepines, they "became more alert, more relaxed, and less
anxious, and this change was accompanied by improved psychomotor
functions." 3 7 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
depressive symptoms. 3 8 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 continuous benzodiazepine use, and
panic attacks and agoraphobia may appear for the first time." 3 9 These
studies and observations told of a very problematic long-term course, and in
2007, French researchers surveyed 4,42 5 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
depressive episodes and generalized anxiety disorder, often with marked
severity and disability."40
In addition to causing emotional distress, long-term
benzodiazepine usage also leads to cognitive impairment. Early on, researchers
recognized that memory problems were associated with short-term use, and this
led David Knott, a physician at the University 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
damage is permanent." 4 1 Over the next twenty-five years, reports of
cognitive 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.4 2 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 "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
impairment—all of these factors contribute to a decline in a person's ability
to function in society. In 1983, the World Health Organization noted a
"striking deterioration in personal care and social interactions" in
long-term benzodiazepine users.4 4 Another investigator reported that they end
up with poor coping skills.4 5 In a study funded by Hoffmann-La Roche, the
manufacturer of Valium, University 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
internal control, poor perceived health and high levels of stress." 4 6
Ashton determined that long-term use led to "malaise, ill-health, and
elevated scores for neuroticism."4 7 Benzodiazepines, she said, contribute
to "jo b loss, unemployment, and loss of work through illness." 48
Such is the history told about benzodiazepines in the
scientific literature. 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 supporting the long-term use of
benzodiazepines for any mental health condition." Benzodiazepines, Gressitt
and his colleagues wrote, may "aggravate" both "medical and
mental health problems." In an interview, 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
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 neurotransmitter system, and in
response, the brain undergoes compensatory 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 dating 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 Geraldine 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,"
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 although it helped for
a short while, months later she still felt something wasn't right and so she
went to see a psychiatrist. "She immediately tells me I have a chemical
imbalance," Geraldine recalls. "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 rehabilitation 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 unless
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 bleeding, the last leading to a hysterectomy.
"All of the women I've known who were on Ativan long-term ended up having
a hysterectomy, every single one of us," she says, with evident bitterness.
At last, in October 1996, she went to a new physician, who, after reviewing her
medical history, identified a likely culprit. "H e told me, 'You are on
one of the most addictive drugs known,' and I thought, '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
addicted 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."
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 musician,
and for a time it went well—he even got to hang out with Carlos 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 benzodiazepine 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 withdrawal 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
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. "M y 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 fashionable
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 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: "M y 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
affluent 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. However, 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 200 2 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 withdrawn? 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 suicidal 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
started crying in class. I couldn't take it anymore, and I
was hospitalized 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 always 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. "M y 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 200 6 Jill
concluded 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 torments: 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
benzodiazepines. 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. "Wha t 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 sunglasses 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.
"M y 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."
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 working, his anxiety had
returned with a vengeance, and he felt physically sick. "I've come to
accept this is my life," he said, his voice filled with what seemed like
bottomless despair. There was, however, 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 people
turning up at mental hospitals, outpatient centers, and residential facilities
for the mentally ill began to sharply rise. The U.S. Department of Health and
Human Services dubs this number "patient care episodes," and it
soared from 1.66 million in 1955 to 6.86
million in 1975, when Valiumania was near its peak. 5 0 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 increase (the emotional struggles
that some Vietnam veterans experienced 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
benzodiazepines 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,
benzodiazepines 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 diagnosis, a 200 6 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 300,00 0 adults in the United States
who received government support in 200 6 due to an anxiety disorder.5 1 That is
roughly sixty times the number of psychoneurotics 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 prescribing of
benzodiazepines for continual use goes on. Indeed, a 200 5 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. 5 2 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. 5 3
8 An Episodic Illness Turns Chronic
"With the range of
available treatments for depression, one might wonder why depression-related
Disability is on the rise."
— CAROLY N DEWA,
CENTRE FOR ADDICTIO N AN D MENTA L HEALTH, ONTARI O (2001) 1
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 2008, 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
ingredients. 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
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 surprising to learn
of this ugly-duckling moment from her past. But with her schoolmates taunting
her, her childhood unhappiness metamorphosed into a deep depression, and when
she was sixteen, she tried to commit suicide by gulping down handfuls of
Benadryl and Valium. She woke up in the hospital, where she was told that she
had a mental illness and was prescribed an antidepressant. "The
psychiatrist 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 psychiatrist 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, someone 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
although 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 graduating, she found a job as an
editorial assistant at a magazine, but depression caught up with her there,
too, and in late 2007, the government deemed her eligible to receive SSDI
because of her illness. "I have always been told that a person has to
accept that the illness 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
despair? 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.
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 depression
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.
"I 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 absurd 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 "disease." 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 "prolonged 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 as possessed by demons. Priests and exorcists would be called upon to
drive out the devils. With the arrival of the Renaissance in the fifteenth
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 category 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.5
Today, Kraepelin's depression-only group would be diagnosed
with unipolar depression, and in the 1960 s and early 1970s, prominent
psychiatrists at academic medical centers and at the NIMH described this
disorder as fairly rare and having a good long-term course. In her 1968 book,
The Epidemiology of Depression, Charlotte Silverman, who directed epidemiology
studies for the NIMH, noted that community surveys in the 1930 s and 1940 s had
found that fewer than one in a thousand adults suffered an episode of clinical
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 hospitals. The total number of depressed
patients in the nation's mental hospitals 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
"ailment 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 Baltimore
psychiatrist Frank Ayd Jr., in his 196 2 book, Recognizing the
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 percent of
Kraepelin's 45 0 "depressed-only" patients experienced but a single
episode of depression, and only 13 percent had three or more episodes.9 Other
investigators in the first half of the twentieth century 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.1 0
Thomas Rennie, who investigated the fate of 142 depressives 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 patients 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
antidepressant era. In 1972, Samuel Guze and Eli Robins at Washington
University Medical School in St. Louis reviewed the scientific literature 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 depression—one in ten—became chronically
ill, Guze and Robins concluded.13
That was the scientific evidence that led NIMH officials
during the 1960 s and 1970 s to speak optimistically about the long-term course
of the illness. "Depression is, on the whole, one of the psychiatric
conditions with the best prognosis for eventual recovery with or without
treatment. Most depressions are self-limited,"
Jonathan Cole wrote in 1964. 14 "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." 1 5 George Winokur, a psychiatrist
at Washington University, advised the public in 1969 that "assurance can
be given to a patient and to his family those subsequent episodes of illness
after a first mania or even a first depression 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 difficult 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
intervention." 17
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, dispiriting
results. The two antidepressants developed in the 1950s, iproniazid 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
1950 s and early 1960 s found both kinds to be wonderfully effective. However,
the studies were of dubious 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 MAO I (phenelzine) was not. Treatment
with this drug was "singularly unsuccessful."18
Four years later, the NIMH conducted a review of all
antidepressant 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 improved
versus 46 percent of the placebo patients, a net benefit of only 15 percent. "The
differences between the effectiveness of antidepressant drugs and placebo are
not impressive," it said. 1 9 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." 20
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 depression. 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 produces an unpleasant side effect of some kind, like dry mouth.)
In six of the seven, there was no difference in outcomes. 21
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 psychotherapy 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. 22
Societal belief in the efficacy of antidepressants was
reborn with the arrival of Prozac in 1988. Eli Lilly, it seemed, had come up 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 concluded 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 198 7 and 2004, determined that thirty-six of the seventy-four
trials had failed to show any statistical benefit for the antidepressants.
There were just as many trials that had produced negative or
"questionable" results as positive ones. 2 4 Finally, in 2008, Irving
Kirsch, a psychologist at the University 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 200 9 editorial in the
British Journal of Psychiatry, had generated "limited valid evidence"
for use of the drugs.2 6 A group of European psychiatrists 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 7 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." 2 8 There
is one other interesting addendum to this research history.
In the late 1980s, many Germans who were depressed turned to
Hypericum perforatum, the plant known as Saint-John's-wort, for relief. German
investigators began conducting double-blind trials of this herbal remedy, and
in 1996, the British Medical Journal summarized the evidence: In thirteen
placebo-controlled trials, 55 percent 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
competition: 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 Americans? 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
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. 2 9
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 symptoms
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 Yugoslavian 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." 5 0 Their symptoms didn't entirely remit, and then, when they
stopped taking the antidepressant, 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 startling: "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 recurrent nature of the vital depression. In
other words, this therapeutic approach was associated with an increase in
recurrent rate and a decrease in cycle duration.... Should [this increase] be
regarded 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; 3 2 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 patients." 3 3 In 1984, Robert Prien at the NIMH reported that 71
percent of depressed patients relapsed within eighteen months of drug
withdrawal. 3 4 Finally, in 1990, the NIMH added to this gloomy picture 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).3 5
Everywhere, the message was the same: Depressed people who
were treated with an antidepressant and then stopped taking it regularly 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 following 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 realization:
"After stopping an antidepressant, symptoms tend to build up gradually and
become chronic." 37
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 1960 s and early
1970s, it wasn't until 1994 that an Italian psychiatrist, Giovanni 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 benzodiazepines 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 offered a biological explanation for what was going on with the
antidepressants. Like antipsychotics and benzodiazepines, these drugs perturb
neurotransmitter systems in the brain. This leads to compensatory
"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.
3 9 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 with great
frequency? Perhaps the drugs cause "irreversible receptor
modifications," Fava said, and, as such, "sensitize" the brain
to depression. 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.4 2 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 antidepressants ineffective but also induce a resident,
refractory depressive 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 the field now confess that these medications might be making
people chronically depressed? That they led to a "malignant"
long-term course? That they caused biological changes in the brain that
"sensitized" 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 NIMH 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 epidemiological
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."4 5 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 edition of the American
Psychiatric Association's Textbook of Psychiatry, it was believed that
"most patients would eventually recover from a major depressive episode.
However, more extensive studies have disproved this assumption."4 6 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 1960 s 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 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. "Antidepressants reduce the risk of relapse in
depressive disorder, and continued treatment with antidepressants would benefit
many patients with recurrent depressive disorder," explained a group of
psychiatrists who reviewed this literature.47
During the 1990s, psychiatrists in the United States and
elsewhere 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 concluded, 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 investigators 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 200 0 report.4 8 The final third of patients see
their symptoms remit over the short term, but only about half of this group,
when maintained on an antidepressant, stay well for long periods of time. 49
In short, two-thirds of patients initially treated with an
antidepressant 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 become "less complete and new
recurrences develop with less provocation." 5 0 This outcomes data
definitely told of a pernicious disorder, but then John Rush, a prominent
psychiatrist at Texas 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 sectors 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
antidepressants 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 decreased 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 remitted and stayed well for a
year. "Most individuals with major depressive disorders have a chronic
course, often with considerable symptomatology and disability even between
episodes," the investigators 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 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 experienced with the antipsychotics: Can it really be that antidepressants,
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 treatment." 5 5
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 outcomes 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 patients 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 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 patients 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
"antidepressant treatment may lead to a deterioration in the long-term
course of mood disorders." 58
* 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 resilience." 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.
A study conducted by the World Health Organization in
fifteen cities around the world to assess the value of screening for depression
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
antidepressants would fare the best, those diagnosed and treated with
benzodiazepines would fare the second best, those diagnosed and treated without
psychotropics the third best, and those undetected and untreated the worst.
Alas, the results were the opposite. Altogether, the WHO investigators
identified 74 0 people as depressed, and it was the 48 4 who weren't exposed to
psychotropic medications (whether diagnosed or not) that had the best outcomes.
They enjoyed much better "general health" at the end of one year,
their depressive 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
antidepressant. The "study does not support the view that failure to
recognize depression has serious adverse consequences," the investigators
wrote. 59
The
WHO investigator s reported that a higher percentage o f the unmedicated group
recovered, an d that "continuing depression " was highest in those
treated with an antidepressant. Source: Goldberg, D.'The effects o f detection
and treatment of major depression in primary care." British Journal of
General Practice 48 (1998): 1840-44.
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 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 56 4
people who subsequently didn't fill a prescription for an antidepressant
returned to work, on average, in 77 days, while the medicated group took 105
days to get back on the job. More important, only 9 percent of the unmedicated
group went on to long-term disability, compared 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 wondered.6 0 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
depression, and they found those who were treated for the illness were three
times more likely than the untreated group to suffer a "cessation" 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 untreated individuals described here had milder
and shorter-lived illnesses [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
* 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
antidepressant returned to work (another 8 percent quit or retired), and
undoubtedly 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.
The Risk of Disability for Depressed Patients
This
was a study of 1,281 employees in Canada WHO went on short-term disability due
to depression. Those WHO too k an antidepressant were more than twice as likely
to goon to long - term disability. Source: Dewa, C "Patter n o f
antidepressant use and duration o f depression - related absence from work.
" British Journal of Psychiatry 183 (2003): 507-13.
Several countries also observed that following the arrival
of the SSRIs, the number of their citizens disabled by depression dramatically
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.6 2 Iceland reported that the percentage of its
population disabled by depression nearly doubled from 197 6 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." 6 3 In the United States, the percentage of working-age
Americans who said in health surveys that they were disabled by depression
tripled during the 1990s. 64
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. "Characteristic s and significance of untreated major
depressive disorder." American Journal of Psychiatry 152 (1995): 1124-29.
There is one final study we need to review. In 2006, Michael
Posternak, a psychiatrist at Brown University, confessed that
"unfortunately, 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 recovering
from an initial bout of depression, subsequently relapsed but did not then go
back on medication. Although these patients were not a "never-exposed"
group, Posternak could still track their "untreated" 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 usually
cleared up within six to eight months, and these results provided "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 unmedicated patients
were recovered after one-month, spontaneous remissions 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
demonstrate 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
without 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 symptoms is not markedly greater than
what is seen in patients treated with a placebo, and this initial use also puts
them onto a problematic 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 likely suffer recurrent episodes of depression, and this chronicity
increases 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 depression 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 200 8 that 58 percent of this group is "severely
impaired." 6 8 That means nearly nine million adults are now disabled, 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 dysfunction, suppression
of RE M 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 Philadelphia 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 abnormalities in frontal-lobe function. None of these
possibilities has been well studied or documented, but something is clearly
going 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 depression, 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 provided
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."
9 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, whichwas themost common medical practice fromthe first
century A.D. until the nineteenth century."
— NASSIR GHAEMI, TUFTS MEDICA L CENTER, APA CONFERENC E
(2008 )
At the American Psychiatric Association's 200 8 annual
meeting in Washington, D.C., there were press conferences each day, and during
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 diseases just like cardiovascular
diseases and cancer," said APA president 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 misinformation."
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 enjoyed. Eli Lilly, Pfizer,
Bristol-Myers Squibb, and the other leading vendors of psychiatric drugs all
had huge welcoming centers, where, 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 finish 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 antipsychotics 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 leaders." 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, during 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 pharmaceutical 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 pharmaceutical company to their list of clients. After Harvard Medical
School's Jean Frazier dutifully relayed such information, at a symposium
devoted 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 pharmaceutical
firms. They regularly opened with a joke before moving on to their PowerPoint
slides, which were splashed on ballroom 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 200 8 APA meeting with its celebrity
patient 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 diagnosable 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 material," 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 information from you and NAM I [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
notebook, 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
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, Frederick
Goodwin and Robert Post, focused on this question: Do antidepressants worsen the
long-term course of bipolar disorder? And notably so?
"The illness has been altered," said Goodwin, who
in 1990 coauthored 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 resistance, and a lot more
lithium treatment failure than there was in the first edition. The illness is
not what Kraepelin described anymore, 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
confessional. 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
depressive episodes. Rapid cycling, Post added, led to a very bad end.
"The number of episodes, and it's a very rich
literature [documenting 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
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 symptomatic and
cognitively impaired, and led to their early death as well. "No w 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
companies "are virtually useless for us as clinicians.... They don't tell
us what we really need to know, what our patients are going to respond 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 "respond 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 questions 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 "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 psychiatry needed to adopt a "Hippocratic"
approach to the use of psychiatric medications, which would require them to
stop prescribing 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 agitated 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
dramatically 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 antipsychotic, 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
descriptions of patients suffering from alternating episodes
of mania and melancholia. "Melancholia," wrote German physician
Christian Vater in the seventeenth century, "often passes into mania and
vice versa. The melancholies now laugh, now are saddened, now express
numberless other absurd gestures and forms of behaviour." The English mad
doctor John Haslam told of how "the most furious 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 folie 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 emotional states all arose from
the same underlying disease. The splitting 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
additional 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 average, 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
As Winokur discovered, the long-term outcomes of the manic
patients 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.4 F. I. Wertham, from Johns Hopkins Medical School, in a 192 9
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 required
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 another 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 hospital 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 asymptomatic 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 difficulty 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 outcomes
literature for this disorder, we need to try to understand this astonishing
increase in its prevalence.9 Although the quick-and- easy explanation is that
psychiatry has greatly expanded the diagnostic 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 marijuana or some other illegal
drug prior to their first manic or psychotic episode.1 0 This substance abuse,
the University of Cincinnati investigators concluded, may "initiate
progressively more severe affective responses, culminating in manic or
depressive episodes, that then become self-perpetuating."1 1 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 200 5 and 200 6 experienced their first bout of
"mood instability" after they had abused illicit drugs.1 2 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 discovery of
this class of drugs. We see tuberculosis patients treated with iproniazid
dancing in the wards, and while that magazine report was probably a bit
exaggerated, it told of lethargic patients suddenly behaving in a manic way. In
1956, George Crane published the first report of antidepressant-induced mania,
and this problem has remained present in the scientific literature ever since.1
4 In 1985, Swiss investigators tracking changes in the patient mix at
Burgholzli psychiatric hospital in Zurich reported that the percentage with
manic symptoms jumped dramatically following the introduction of
antidepressants. "Bipolar disorders increased; more patients were admitted
with frequent episodes," they wrote. 1 5 In a 1993 practice guide to
depression, the APA confessed that "all antidepressant treatments,
including EC T [electroconvulsive therapy], may provoke manic or hypomanic
episodes." 1 6 A few years later, researchers at Yale University School of
Medicine quantified this risk. They reviewed the records of 87,29 0 patients
diagnosed with depression or anxiety between 1997 and 200 1 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. 1 7 As a result, over longer periods, 20 to 40 percent of all
patients initially diagnosed with unipolar depression today eventually convert
to bipolar illness.1 8 Indeed, in a recent survey of members of the Depressive
and Manic-Depressive Association, 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," explained Fred Goodwin, in a 200 5 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 stimulation." 2 0 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
commonplace today. SSRIs took the country by storm in the 1990s, and from 1996
to 2004, the number of adults diagnosed with bipolar illness rose 56 percent.
At the same time, psychiatry's steady expansion 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
hospitalization. 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 (hypomania), he or she could be diagnosed
with bipolar II, a less severe form of the disease. Then the bipolar II
diagnosis was expanded 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 diagnostic boundaries expanded
in this way, researchers were suddenly announcing 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
"subthreshold" symptoms of depression and mania, and thus could be
diagnosed with "bipolar spectrum disorder."2 2 There was now bipolar
I, bipolar II, and a "bipolarity intermediate between bipolar disorder and
normality," one bipolar expert explained.2 3 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
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 suffered from gout. In the
late 1800 s 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 eventually found to have no uric-acid-dissolving properties, and in
1949, the FDA banned it after it was found to cause cardiovascular problems.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 intellectual 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
interest 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 researchers who
scoured the scientific literature could only find four of any merit. However,
in those studies, lithium produced a good response in 75 percent of the
patients, which was much higher than the response rate in the placebo group. 2
7 The second part of the evidence base for lithium came, as usual, from
withdrawal studies. Investigators who analyzed nineteen such trials in 1994
found that 53. 5 percent of the patients withdrawn from lithium relapsed, versus
37. 5 percent of the lithium-maintained patients. That was taken as evidence
that lithium prevented relapse, although the researchers 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
patients). 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 emergency 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 relapsed at astonishingly high
rates. In 1999, Ross Baldessarini reported that half of all patients relapsed
within five months of quitting 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.2 9 "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. 3 0 Other
investigators noted the same phenomenon: "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.3 2 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 drug may be "harmful to bipolar patients." The
higher hospitalization readmission rates for bipolar patients since the
introduction of lithium "could be explained entirely" by this
drug-induced worsening, 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. 3 4 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.3 5
This was a dismal finding, and then Michael Gitlin at UCLA reported similar
five-year results for his lithium-treated bipolar patients. "Even aggressive
pharmacological maintenance treatment does not prevent relatively poor outcome
in a significant number of bipolar patients," 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 associated with
various forms of harm." 37
Bipolar All the Time
There are really two narratives to be dug out of the
scientific literature 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 dramatically
worsened during the psychopharmacology era, with experts in the field
documenting this at every turn.
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 intervals 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 depression." 3 8
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 1960 s and
1970 s told of two-thirds who were becoming chronically ill. "The
administration 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... induction 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
medications 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 recurrences 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 unknown, 16 percent of
Koukopoulos's manic-depressive patients were now in this predicament, and they
were suffering an astonishing 65 mood episodes annually, up from less than one
episode a year prior to being treated with an antidepressant. "It
certainly seems paradoxical," 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 prescribed to bipolar patients, and even today, 60 to 80 percent are exposed
to an SSRI or some other antidepressant. As a result, investigators have
continued to document the harm done. In 2000, Nassir Ghaemi reported that in a
study of thirty-eight bipolar patients 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 depressed" than a second group of bipolar patients who weren't
exposed to this class of medication.4 1 "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. 4 2
At the University of Louisville, Rif El-Mallakh similarly concluded that
antidepressants may "destabilize the illness, leading to an increase in
the number of both manic and depressive episodes." The drugs, he added,
"increase the likelihood of a mixed state," in which feelings of depression
and mania occur simultaneously.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 rapidly with unmodified
severity" for years on end. 4 4 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 miserable. 4 5 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 antidepressant use,
which about 60 percent of patients received," Ghaemi noted. 4 6 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.47 "This study," wrote Ghaemi, in an editorial
that appeared in the American 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 depressed 32 percent of the time,
manic or hypomanic 9 percent of the time, and suffering from mixed symptoms 6
percent of the time. 4 8 The bipolar II patients in that study arguably fared
even worse: They were depressed 50 percent of the time. "The nature of
this deceptively 'milder' form of manic-depressive illness is so chronic as to
seem to fill the entire life," Judd wrote. 4 9 Russell Joffe, at the New
Jersey Medical School, reported in 200 4 that 33 percent of the bipolar 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. 5 0
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 200 0 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 concern: 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 relatively rare occurrence," Zarate and Tohen
wrote. "However, modern outcome studies have found that a majority of
bipolar patients evidence high rates of functional impairment." What, they
wondered, could explain "these differences"? 53
The remarkable decline in the functional outcomes of bipolar
patients is easy to document. In the pre-lithium era, 85 percent of mania patients
would return to work or to their "pre-morbid" social 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 investigators were reporting that fewer than half of all
bipolar patients 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.5
4 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 percent had
attended college and 30 percent had graduated, two-thirds were unemployed.5 6
"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." 5 7
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 200 0 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 investigators compared
cognitive function in bipolar and schizophrenia patients, and they concluded
that while the bipolar patients showed signs of impairment, the deficits were
"more severe and extensive in schizophrenia." 58
This was something of a glass-half-full finding. You could
interpret 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."5 9 The degree of
impairment in these two illnesses was suddenly converging, and in 2001, Faith
Dickerson at the Sheppard Pratt Health System in Baltimore provided 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 cognitive 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. "O n
most measures of social functioning, 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 investigators all told
of it. The Australians reported in 200 7 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.6 1 Meanwhile, Spanish investigators,
after noting that cognitive function in their bipolar and schizophrenia patients
"did not differ over time in any test," concluded that both groups
suffered from dysfunction in the "prefrontal cortex and temporolimbic
structures." They also observed that "the more medications the
patients received, the greater the psychosocial functioning impairment." 6
2 * Finally, 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 impoverished
as those diagnosed with schizophrenia.63
This was an astonishing convergence in long-term outcomes
between 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." 6 4 Later, he and Tohen
wrote that "medication induced changes may be yet another factor in
explaining the discrepancies in recovery rates between earlier and more recent
studies." 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." Cognitive impairment was a primary reason that medicated
schizophrenia patients fared so poorly over the long term, they said, ancl
"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 disorder
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 dysfunction,
etc.—and wondered whether "treatment factors such as toxicity from
medications" could be causing these devastating ailments, 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.
stating that the drugs might be causing this mental and
physical deterioration in their patients. But it's easy to see that their
hesitancy 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 pharmacological 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." 6 7 Psychiatric drugs, of course, perturb various
neurotransmitter pathways in the brain, and thus once schizophrenia and bipolar
patients are on similar drug cocktails, they suffer from similar abnormalities
in brain function. The convergence 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 incomprehensibly worse. In his 200 7 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
unclear what percentage of people diagnosed with schizophrenia today, if not
continually medicated, would deteriorate cognitively over time.
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 t o 50 |
Goo d long-term functional outcomes |
7 5 % t o 90 % |
33 % |
Symptom course |
Time-limited acute episode s o f mania an d major
depression with recovery to euthymia
and a favorable functional adaptation between episodes |
Slow or incomplete recovery from acute episodes,
continued risk of recurrences, and sustained morbidity over time |
Cognitive function |
No impairment between episodes 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 schizophreni a |
This
information is drawn from multiple sources. See in particular Huxley, N.
"Disability and its treatment in bipolar disorder patients." Bipolar
Disorders 9 (2007): 183-96.
era, there was "recovery to euthymia [no symptoms] and
a favorable 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 occupational
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.6 8
The Graphic That Tells It All
We are now coming to the close of our examination of the outcome’s
literature for the major psychiatric disorders (for adults), and a return to
Martin Harrow's fifteen-year study on schizophrenia outcomes brings it to a
climactic end. In addition to following schizophrenia patients, Harrow studied
a group of eighty-one patients 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 expect 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" category
(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 asymptomatic. 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
remained 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 patients who were off meds
improved, the manic-depressive patients who kept taking their pills did not,
such that by the end of 4. 5
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 illness 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 outcome’s 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
12,75 0 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
I n
this graphic, the group labeled "manic depressive " consisted of
psychotic patient s with bipolar illness, unipolar depression, and milder
psychotic disorders. Source: Harrow, M. "Factor s involve d
in
outcome an d recovery in schizophrenia patients not on antipsychotic
medications. " The Journal of Nervous and Mental Disease, 195 (2007):
406-14.
United States with this diagnosis, and according to
researchers at the Johns Hopkins School of Public Health, 83 percent are
"severely impaired" in some facet of their lives.7 0 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 suffered 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 diagnosed
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 had been turned into a mental patient, and
Dorea would have continued 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 "recover" 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 antidepressants, 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 antidepressants exacerbated my illness."
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 people 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
allegiance 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 struggled with mood swings even
as a kid, and at age sixteen, while hospitalized 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 explains, and
while he suffered several bouts of depression, he did well in between those
episodes, particularly when he was in a slightly hypomanic 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 depression 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
psychiatric 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 antidepressants
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 published 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 continuing to worsen.
"I would say in the main, I have been worse when taking
medication. 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."
Brandon Banks
Brandon Banks can identify the precise moment he became
"bipolar," 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,
Kentucky, 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
antidepressants, and as time went on he became a rapid cycler who suffered from
mixed states. His medical records also document the development of new
psychiatric symptoms: worsening anxiety, panic attacks, 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
driver's license. "What my life became was staying at home all day, getting
up in the morning and laying my pills out on the counter, taking 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 transformative experience. By the time he
returned home, he had sworn off eating 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 2008-200 9 year at Elizabethtown Community and Technical
College. He enrolled there in January of 200 8 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 Kentucky Intercollegiate Press Association during the 2008-200 9 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 successes too. One of his short
stories won second place in a competition 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
sophomore" award. Yet, even during this season of remarkable
accomplishment, Brandon suffered several hypomanic and depressive
episodes that left him feeling deeply suicidal. "I
spent several weekends reading depressive authors with a gun in my hand,"
he says. "My accomplishments at these moments just seem to make everything
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 illegal 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 psychiatrists 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 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 200 4 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 25 5 pounds to nearly 50 0 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 coming 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 illness, 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 engineering, 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 expected 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 mathematician 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
person 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 insecurity?' I just
have to take the time to check myself." He is, he concluded, "pretty
optimistic about my future now."
10
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."
— AM Y UPHAM (2009) 1
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 curious 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 disorders, 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 clinical
experience. Prior to 1955, history tells us, the state mental hospitals 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 researchers 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 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 without it."
Young
or old woman? If you shift your eyes slightly, you r perception of the image
will change from one to the other. Courtesy of Exploratorium.
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 medicine. 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 diseases
stumbled upon several agents that had novel side effects. Then, over the course
of the next thirty years, researchers determined 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 outcome’s
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
hundred pounds. Often, their blood sugar levels soar, and so do their
cholesterol levels. A number of those struck by the mysterious
illness—including young children and teenagers—become diabetic in fairly short
order. Reports of patients occasionally dying from pancreatitis appear in the
medical literature. Newspapers and magazines fill their pages with accounts of
this new scourge, which is dubbed metabolic dysfunction illness, and parents
are in a panic 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, MR I
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. Relationships 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.
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 children and adults into the
mental illness camp. Second, those so diagnosed 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 symptoms, 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 suffering a first
episode of psychosis were discharged from the hospital within eighteen months,
and the majority didn't return to the hospital 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 depression, 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
function 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 affective 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
expanded 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 Security
Administration released its 200 7 reports for its SSI and SSDI programs, and
the numbers were as expected. There were 401,25 5 children and adults under
sixty-five years old added to the SSI and SSDI rolls in 200 7 because of a
psychiatric disability. Imagine a large auditorium filling up every day with 25
0 children and 850 adults newly disabled by mental illness, and you get a
visual sense of the horrible toll exacted by this epidemic.
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 cardiovascular
ailments, respiratory problems, metabolic illnesses, diabetes, kidney failure,
and so forth—the physical ailments tend to pile up as people stay on
antipsychotics (or drug cocktails) for years on end.3
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 hypomanic episodes and
worsened her obsessive-compulsive behaviors. Finally, in 2007, she decided to
gradually wean herself from the two-drug combo she was taking, and at first, it
went well. However, 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 Abilify, which triggered a
seizure. Next a doctor discovered something wrong with her heart, which
appeared to be related to the Klonopin, and so Amy was put back on Ativan.
"No w I start hallucinating for the first time in my life," she says.
"I was pacing 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
papers 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 withdrawals 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."
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 MI T 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 Xana x was a disaster. That is the evilest drug ever. It is so
addictive, and all of the symptoms that caused you to go into the hospital in
the first place get one thousand times worse when you try to go off it."
Although Rachel eventually graduated from MI T and was
accepted into an M.D.-Ph.D. program at the University of Colorado, she began
cycling in and out of hospitals; her crash at MI T transformed 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 assistant 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
says, shaking her head at the memory. "It caused
vasoconstriction in my brain, and this caused brain damage. I ended up in a
wheelchair, 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 useful 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 MB A 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 depression (he'd suffered a first
episode five years earlier, when his parents 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 200 6 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.
"H e was five feet, ten inches tall and he went from 185 pounds to 25 0
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 Thanksgiving, 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
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
[laboratory] 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 Houston 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."
I I
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
( 2006 ) 1
The prescribing of psychiatric drugs to children and
adolescents is a recent phenomenon, as relatively few youths 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 scientific
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 results 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 adolescents 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 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 elementary 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
society'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
adolescents. Here's how Harvard Medical School psychiatrist Ronald Kessler
summed up this "history" in 2001:
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 disturbance 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 manialike 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
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 200 6 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 glutamates, 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
"neuroprotective" 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 Frederick Still, a
British pediatrician, published a series of lectures on twenty children who
were of normal intelligence but "exhibited violent 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
bad parenting). Children with known diseases—epilepsy, brain
tumors, 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 recovered
from encephalitis lethargica, a viral epidemic that swept around the globe from
1917 to 1928, often exhibited antisocial behaviors and severe emotional swings,
leading pediatricians to conclude 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 "normal brain injured
children." 5 Psychiatry's first Diagnostic and Statistical 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
amphetamine, 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 concentrate better on their
schoolwork. The children dubbed Benzedrine the "arithmetic pill." 6
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 1960 s
to prescribe 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 children, or children in
residential facilities. The population of children so hyperactive that they
might be diagnosed with "organic brain
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, psychiatry 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 Attention 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 Individuals with Disabilities Education
Act. Children diagnosed with ADH D 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 200 7 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 ADH D 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 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."1 0 During
the 1990s, CHAD D advised the public that children with ADH D suffered from a
chemical imbalance, characterized 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 attempting 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 neurochemical 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 suffered
from brain dysfunction of some kind, which was certainly a reasonable thought,
but the nature of that dysfunction was never discerned, and then, in 1980,
psychiatry simply created, with a stroke of its pen in DSM-III, a dramatically
expanded definition of "hyperactivity." The fidgety seven-year-old
boy who might have been dubbed a "goof-off" in 197 0 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. Cocaine 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
relatively brief disruption of this function.
* 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 wan t to
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 compensatory 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 "qualitatively 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 ADH D drugs do reliably change a child's
behavior, and in his 1937 report, Charles Bradley set the stage for the efficacy
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." 1 5 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 come s when dopaminergic pathways are first sent into a hyperactive state.
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 spontaneity, 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.14
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 interactions,"
announced Russell Barkley, a psychologist at the Medical College of Wisconsin,
in 1978. 1 5 This drug, observed Bowling Green State University psychologist
Nancy Fiedler, reduced a child's "curiosity about the environment." 1
6 At times, the medicated child "loses his sparkle," wrote Canadian
pediatrician Till Davy in 1989. 1 7 Children treated with a stimulant,
concluded a team of UCLA psychologists in 1993, often become "passive, submissive"
and "socially withdrawn." 1 8 Some children on the drug "seem
zombie-like," noted psychologist James Swanson, director of an ADHD center
at the University of California, Irvine.1 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." 20
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 student wouldn't move around
as much and wouldn't engage as much socially with his or her peers. If given a
task like answering arithmetic 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 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 classroom
disturbance."2 1 ADH D experts at
Massachusetts General Hospital summed up the scientific literature in a similar
way: "The extant literature clearly documents that stimulants diminish
behaviors prototypical of ADHD, including motoric overactivity, impulsivity,
and inattentiveness."22
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
friendships, stimulants produced "few significant positive effects and a
high incidence of negative effects," Jacobvitz said. 2 4 Other researchers
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 control 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
depressed, 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
on a math test, it turned out, didn't translate into
long-term academic 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." 2 7 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 academic performance." 2 8 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. 2 9 Carol Whalen, a psychologist from the
University of California 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
investigators 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
researchers 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.3 2 Nor was there evidence that staying on a stimulant led to a
sustained improvement in behavior. "Teachers and parents should not expect
long-term improvement in academic achievement or reduced antisocial
behavior," Swanson wrote in 1993. " The 1994 edition of the APA's
Textbook of Psychiatry admitted to the same bottom-line conclusion:
"Stimulants do not produce lasting improvements in aggressivity, conduct
disorder, criminality, education achievement, job functioning, marital
relationships, or long-term adjustment." 3 4 Thirty years of research had
failed to provide any good-quality evidence 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 Treatment 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 ADH D 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 director of child and adolescent research at the NIMH, acknowledged
during the planning stages that there was no evidence in the scientific
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 efficacy" 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. 3 6
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
"superior" 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 subjects), and as a result,
psychiatry now had a long-term study that documented the continuing benefits of
stimulants. "Since ADHD is now regarded by most experts as a chronic
disorder, ongoing treatment often seems necessary," the researchers
concluded.37
After that initial fourteen-month period of treatment, the
investigators followed up periodically with the students, assessing how they
were doing and whether they were taking an ADHD medication. This was now a
naturalistic study much like the one that Martin 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 significant
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
symptoms—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. Medication 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 ADH D is a
"real" disease, but this study showed that when it comes to using
stimulants to treat it, the controversy is moot. Even if ADH D is real,
stimulants aren't going to provide long-term help. "We had thought that
children medicated longer would have better outcomes. That didn't happen 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, |medication] will help the child
behave better, in the long run it won't. And that information should be made
very clear to parents." 41
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 nothing 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 ADH D 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
hostility toward the world. The psychiatric problems include obsessive-
compulsive symptoms, mania, paranoia, psychotic episodes, and hallucinations.
Methylphenidate also reduces blood flow and glucose metabolism in the brain,
changes that usually are associated with "neuropathologic states." 4
2
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. 4 3 Various rat studies
suggested that lengthy exposure to methylphenidate might cause dopaminergic
pathways to become permanently desensitized, and since dopamine is the brain's
"reward system," medicating the child may produce an adult with a
"reduced ability to experience pleasure." 4 4 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
brain is still developing "results in aberrant behavioral adaptations
during adulthood." 45
Such is the outcomes literature for Ritalin and other ADH D
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 physiological 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 25 0 children under nineteen years of age in the United States was
taking an antidepressant.4 6 That was partly due to a cultural belief that
youth were naturally moody and recovered quickly from depressive 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 200 2 one in every forty children under nineteen years of age in the United
States was taking an antidepressant.4 8 Presumably these drugs provide a
short-term benefit to children and adolescents that the tricyclics fail to
provide, but unfortunately, 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 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 institutional failure," the Lancet wrote in a
200 4 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. During
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 anguished parents telling of how their children had killed themselves
after going on an SSRI, the FDA was forced to hold a hearing in 200 4 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 randomized onto Prozac were
evaluated for a week, and only those "who adapted well" to the drug
were then enrolled in the study.
This helped increase the drug response rate. "Before
the study even started," explained Jonathan Leo, editor in chief of the
journal Ethical 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."5i 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 entirely from a
secondary "improvement" scale filled out by the psychiatrists paid by
Eli Lilly to run the trial.
Such was the record of efficacy produced by the SSRIs in
pediatric 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." 5 2 The truth, explained the Lancet
editors in an accompanying editorial, was that these drugs "were both
ineffective and harmful in children." 5 3 Australian scientists chimed in
with a similar 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 reviewed 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." 5 4
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 dysfunction, headaches,
gastrointestinal problems, dizziness, tremors, nervousness, muscle cramps,
muscle weakness, seizures, and a severe inner agitation known as akathisia,
which is associated with an increased 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 review
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. "On e 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 impairing."
5 5 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." 5 6 Other physicians 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.' " 5 7 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 ADH D 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-
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 beginning to prove that the
disorder can begin very early in life and that it is far more common than was
previously supposed." 5 8 Yet the rise in the number of children and
adolescents with this diagnosis 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. 5 9 "Ne w awareness of the
disorder 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 explanation 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
condition 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 pediatricians 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
psychosis in children." 6 1 An Ohio physician, Louis Lurie, reviewed the 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 2,20 0 psychiatric patients five to sixteen years old, and found
only two instances of manic-depressive illness. 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 depression 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 1960 s and early 1970s, psychiatrists began prescribing
Ritalin 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,
Weinberg 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 Massachusetts 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 amphetamines, methylphenidate, or "other medications to
affect behavior." 6 6 Then, in 1982, Michael Strober and Gabrielle Carlson
at the UCLA Neuropsychiatries Institute put a new twist into the juvenile
bipolar story. Twelve of the sixty adolescents they had treated with
antidepressants had turned "bipolar" over the course of three 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
antidepressant. "Ou r data imply that biologic differences between latent
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 syndromes in juveniles," they said. 67
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 children 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.6 8 Three years later, Carlson reported that 63 percent of the
pediatric patients treated at her university hospital suffered from mania, the
very symptom that doctors in the pre-psychopharmacologic era almost never saw in
children. "Manic symptoms are the rule, rather than the exception,"
she noted. 6 9 Indeed, Lewinsohn's epidemiological data was now already out of
date. The number of children discharged from hospitals with a bipolar diagnosis
rose fivefold between 1996 and 2004, such that this "ferocious mental
illness" was now said to strike one in every fifty prepubertal children in
America. "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."70
An epidemic had come of age, and history reveals that it
rose in lockstep with the prescribing of stimulants and antidepressants to
children.
Creating the Bipolar Child
Given that chronology, we should be able to find data that
explains why stimulants and antidepressants would have that iatrogenic effect.
There should be data showing that if you treat 5 million children 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 dopamine 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
physician at the University of California at San Diego School of Medicine,
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 suffer a
manic or psychotic episode. Although this risk isn't well quantified, 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." 7 2 In 2006, the FDA issued a report on this
risk. From 200 0 to 2005, the agency had received nearly one thousand reports
of stimulant-induced psychosis and mania in children and adolescents, and given
that these MedWatch reports are thought to represent only 1 percent of the
actual number of adverse events, this suggests that 100,000 youths diagnosed
with ADH D suffered psychotic and or manic episodes during that five-year
period. The FDA determined that 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. 7 3
Once this drug-induced psychosis occurs, the children are usually
diagnosed with bipolar disorder. Moreover, this diagnostic progression, from
medicated ADHD to bipolar illness, is well recognized by experts in the field.
In a study of 195 bipolar children and adolescents, Demitri Papolos found that
65 percent "had hypomanic, manic and aggressive reactions to stimulant
medications." 7 4 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 withdrawal, 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
energy, social isolation, a loss of interest in activities (apathy), and a sad
mood.
The ADHD to Bipolar Pathway
Stimulant-Induced Symptoms |
Bipolar Symptoms |
||
Arousal |
Dysphoric |
Arousal |
Dysphoric |
INCREASED ENERGY |
SOMNOLENCE |
INCREASED ENERGY |
SAD MOOD |
INTENSIFIED FOCUS HYPERALERTNESS EUPHORIA |
FATIGUE, LETHARGY SOCIAL WITHDRAWAL, ISOLATION |
INTENSIFIED GOAL- DIRECTED ACTIVITY DECREASED NEED FOR SLEEP |
LOSS OF ENERGY LOSS OF INTEREST IN ACTIVITIES |
AGITATION, ANXIETY |
DECREASED SPONTANEITY |
SEVERE MOOD CHANGE |
SOCIAL ISOLATION |
INSOMNIA IRRITABILITY HOSTILITY |
REDUCED CURIOSITY CONSTRICTION OF AFFECT DEPRESSION |
IRRITABILITY AGITATION DESTRUCTIVE OUTBURSTS |
POOR COMMUNI• CATION FEELINGS OF WORTH- LESSNESS |
HYPOMANIA MANIA |
EMOTIONAL LABILITY |
INCREASED TALKING DISTRACTIBILITY |
UNEXPLAINED CRYING |
PSYCHOSIS |
|
HYPOMANIA |
|
|
|
MANIA |
|
STIMULANTS USED TO TREAT 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 quantified. Joseph
Biederman and his colleagues at Massachusetts General Hospital reported in 1996
that 15 of 140 children (11 percent) diagnosed with ADHD developed bipolar
symptoms—which were not present at initial diagnosis—within four years. 7 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 400,00 0 bipolar youth. As Time noted, most children
with bipolar illness are diagnosed with a different psychiatric disorder first,
with "ADH D 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
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.7 7 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 8 Luvox,
meanwhile, was reported to cause a 4 percent rate of mania in children under
18. 7 9 In 2004, Yale University researchers 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.8 1 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 bipolar.8 2
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 500,00 0 to 1 million bipolar youth.
We now have numbers that tell of an iatrogenic epidemic:
400,00 0 bipolar children arriving via the ADH D 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 200 3 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. 8 3 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 to an antidepressant.8 4 Finally, Gianni Faedda found that 84
percent of the children treated for bipolar illness at the Luci Bini Mood
Disorders Clinic in New York City between 1998 and 200 0 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 ADHD 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 language, parents call this "bouncing off the
wall." First hospitalization occurred often among our children during manic
or mixed states (including suicidal gestures and attempts) triggered 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 200 2 article titled
"Crisis on the Campus," Psychology Today reported that an increasing
number of students, having arrived at college with an antidepressant 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.
8 7 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 bipolar
illness in their country. Dutch investigator Catrien Reichart then studied the
offspring of parents with bipolar disorder in both the United States and the
Netherlands, and determined that the Americans 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 antidepressants and stimulants to children in the U.S. is much
higher."8 8 All of this tells of an epidemic that is mostly iatrogenic in
kind.
Fifty years ago, physicians virtually never saw
manic-depressive illness in preteens, and they rarely diagnosed it in
adolescents. Then pediatricians and psychiatrists began prescribing Ritalin to
hyperactive 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 biological 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 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 associated 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 picture 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 constantly
switching between manic and depressed mood states.9 0 Similarly, 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 cycling only a little bit less extreme.
"In contrast to a biphasic, episodic and relatively slow cycling course in
some adults with bipolar disorder, 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 patients, 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." 9
2 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 postpubertal onset bipolar to
recover," he said, and it was "expected that children will be poor
responders to treatment when they become adults." 9 ' DelBello followed a
group of adolescents hospitalized for a first bipolar episode and concluded
that only 41 percent functionally recovered within a year.9 4 This impairment,
Birmaher determined, then worsens after the first year. "Functional
impairment in bipolar appears to increase during adolescence regardless of age
of onset." 95
Youth diagnosed with bipolar illness are typically put on
drug cocktails that include an atypical antipsychotic and a mood stabilizer.
This means that they now have multiple neurotransmitter pathways 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 receive a neuroleptic." 9 6 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 antipsychotics cannot be
recommended for children diagnosed with bipolar disorders," said Elisabeth
Houtsmuller, senior analyst for Hayes. 9 7 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 drugs will induce cognitive decline, and the child who stays on
the cocktails into adulthood can expect to die early as well.
------------
* In a
200 8 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 hormon
e 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.
-----------------------
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
volumes about the havoc that is being wreaked. There were 16,20 0
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 561,56 9 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 22,45 3 in 200 0 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.9 9 The deteriorating
mental health of the nation's children, declared U.S. surgeon general David
Satcher in 2001, constituted "a health crisis." 1 0 0 Next, colleges
were suddenly wondering why so many of their students were suffering manic
episodes or behaving in disturbed ways; a 200 7 survey discovered that one in
six college students had deliberately "cut or burned self" in the
prior year.10 1 All of this led the U.S. Government Accountability Office to
investigate what was going on, and it reported in 200 8 that one in every
fifteen young adults, eighteen to twenty-six years old, is now "seriously
mentally ill." There are 680,00 0 in that age group with bipolar disorder
and another 800,00 0 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 institutionalized. All of these youth are
"functionally impaired" to some degree, the GAO said. 1 0 2
The
Epidemic Hits America's Children
SSI Recipients Under 18 Years Old Disabled by Mental Illness, 1987-2007
Prior to 1992, the government's SSI reports did not break
down children recipients into subgroups by age. Source: Social Security
Administration reports, 1987-2007.
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.
12
Suffer the Children
"You wonder
all the time: Are you helping or harming
your child?"
— jasmine' s mo m (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 children have been helped by psychiatric drugs, and
given the spectrum of outcomes that occur with this paradigm of care, that is
undoubtedly 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.
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 willing 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"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."
* Since "Jasmine " could
not give consent to having her nam e used, her mother and I agreed to keep her
identity hidden. I've also kept her mothe r unnamed for that same reason.
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
violence. "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 diagnosed 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 principal'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
stabilized fairly well on a combination of Zyprexa and Depakote. Although she
rarely socialized with classmates, she did well academically, and during her
first years in high school, she regularly earned A's and kudos for her
photography and artwork. She immersed herself 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 wondered what happened
to me?' She was so brave."
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 excursion 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 "escaped" 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 person
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, communicating through singing."
But in early 2007, Jasmine suffered another 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.
"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 nothing 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 summarized 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 crying 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
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 stimulants,
including Adderall, Concerta, and dextroamphetamine. "It was always more
drugs," his mother says.
Meanwhile, Andrew's success in the classroom fluctuated
according 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. "M y
Andrew is not a circle or a square, he is not even a triangle," she
explains. "H e 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 medicine, he would
have learned many more coping mechanisms, because 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 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 skateboarding 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
medications. "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 husband, 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 stepfather, 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 watching 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 stabilizer to be extremely
helpful, and she remains on those drugs.
As a foster mother, Gately was required to follow
"medical advice" 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. "On e 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." Another 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 children, concluding that "maybe nine to eleven [of the
ninety-six children] 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 almost 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 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 diagnoses 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 Westchester 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 suffer from bipolar disorder at a greater rate than whites.1 The
diagnosis 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 fucking in cahoots,
and they are doing a wicked dance with a lot of people'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 junior 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 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 isolated,"
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 explains, 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 handcuffs 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
Massachusetts. The council is composed of young adults who entered the mental
health system before they were eighteen, and it provides advice 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.
he "wanted to kill the other kid," a sentiment
that earned him a trip to a psychiatric facility, where he was diagnosed with
bipolar illness. "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
discharged, preferring to smoke marijuana instead, and inevitably that leads to
trouble. "I get arrested and get sent back to the (psych) hospital, 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 diagnosed 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 cocktails, moving about and
speaking in a sluggish manner, the one who had told of having killed somebody
was now living in the community 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
the two families conflicting advice about whether they
should medicate 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 struggles," 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 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. "H e said he wants to start being more
responsible," his mother said. "H e 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 explained, in a phone interview in early
2009. "The ADHD is fine and under control. If this doesn't work, they will
give him an antianxiety 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 witnessed 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 invisible 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. "H e 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 confessed 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 alone in this," his
mother says. "It stinks. It's wearing. It's exhausting. 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
13
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
SOUTH WEST MEDICAL CENTER IN
DALLAS, TEXA S (1995) 1
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
fashion, 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 literature 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 psychiatry" 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 the rest of
medicine, and once NIMH researchers and others advanced the chemical imbalance
theory of mental disorders, it seemed that these pills might indeed be
antidotes to physical diseases. "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
psychiatry was mired in a deep crisis, beleaguered on so many fronts that it
worried about its survival. There was a sense, said American Psychiatric
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
intellectual 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 applied 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
publications 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 malevolent cop in that movie, which ended with Randle McMurphy (played by
Jack Nicholson) being lobotomized for failing to stay in line.
The second problem that psychiatry faced was a growing
competition for patients. In the 1960 s 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 1960 s 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 1970 s 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 psychiatrist 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 1950 s had never completely 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 faction 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, altering
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 crisis," Sabshin said.7
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,
psychiatry 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 illness 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 nuisance. 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 remained 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 and unnecessary. Psychiatry fell into a crisis during the 1970
s because the "miracle pill" aura around its drugs had disappeared.
From the moment that Thorazine and the neuroleptics were
introduced 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 injectable forms of their neuroleptics so that
hospitalized patients could be forcibly medicated. "Warning!" an ad
for liquid Thorazine screamed. "Mental Patients Are Notorious DRU G
EVADERS." 9 In the early 1970s, patients who had experienced such forced
treatment began forming groups with names such as the "Insane Liberation
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." 1 0 Then, in 1975, when Indiana
senator Birch Bayh launched an investigation of the use of neuroleptics in
juvenile institutions, 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 disrepute. The federal
government classified them as schedule IV drugs, and soon Edward Kennedy was
announcing that benzos
had "produced a nightmare of dependence and
addiction." 12 Antipsychotics 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 prescriptions in 1973 to 153 million in
1980. 1 3 In its article on psychiatry's "anxious years," the New
York Times explained that a primary reason 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 acknowledge. 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 1970 s when
a keynote speaker laid it out for them: "He said, 'What is going to save
us is that we're physicians,' " Piatt recalls. 1 4 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 psychotropic 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. 1 5 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 physician." 1 6 Mental disorders, said Paul Blaney,
from the University of Texas, were to be seen as "organic diseases."
1 7 The psychiatrist's focus should be on making the proper diagnosis, which
arose from 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 application of
the most effective treatments available today for psychiatric patients:
psychoactive drugs and EC T [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 trotted 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
University 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 "unreliable." He was joined by
four other biologically oriented psychiatrists 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."
2 0 The manual, said APA president Jack Weinberg in 1977, would "clarify
to anyone who may be in doubt that we regard psychiatry as a specialty of
medicine." 21
Three years later, Spitzer and his colleagues published
their handiwork. DSM-III identified 26 5 disorders, all of which were said to
be distinct in kind. More than one hundred psychiatrists had contributed 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 m"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 subjective 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
document... a brilliant tour de force," Sabshin said. 2 3 "The
development 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." 2 4 Thanks to
DSM-III, wrote Columbia University psychiatrist Jerrold Maxmen, "the
ascendance of scientific psychiatry became official... 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." 2 6 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 Association, was more of
"a political position paper for the American Psychiatric Association than
a scientifically-based classification system." 27
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 embrace the medical model.
"It is time to state forcefully that the identity crisis is over,"
Sabshin said. 2 8 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 patients and prestige." 2 9 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
understood that it threatened the "medical model" theory of psychiatric
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 oversaw NIMH' s extramural
research program, which was composed of psychiatrists from leading medical
schools, and that committee slashed his initial request of $700,00 0 for five
years to $150,00 0 for two years. This ensured that the project would struggle
with finances 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." 3 1 Mosher must
be biased, the academic psychiatrists concluded, and they demanded that Mosher
be removed as the primary investigator. "The message was clear,"
Mosher said, in an interview twenty-five years later. "If we were getting
outcomes this good, then I must not be an honest scientist." 3 2 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 committee
had grudgingly concluded, in its final review of the project, that "this
project has probably demonstrated that a flexible, community 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
"medical model" to the public. Although professional medical
organizations 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 commercial trade association.
In 1981, the APA established a "division of publications and
marketing" to "deepen the medical identification 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
knowledge before the reading public." 3 5 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 organization's elected officials—worried anew
about this concern. "Ho w do we organize 32,00 0 members for
advocacy?" he asked. " WHO should be allowed to speak to the issue of
the treatment of 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
develop a nationwide roster of "experts" that could promote the
medical-model story to the media. It established a "public affairs
institute" to oversee this effort, which involved training members
"in techniques for dealing with radio and television." In 1985 alone,
the APA ran nine "Ho w to Survive a Television Interview" workshops. 3
8 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 leaders 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 positive coverage.
In December 1980, it held a daylong media conference on "new advances in
psychiatry" that "was attended by representatives of some of the
nation's most prestigious and widely circulated newspapers," Sabshin
crowed. 4 0 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 carried the
medical-model message to listeners around the country.4 1 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."4 2 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 headlines
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." 4 4 Societal belief in biological psychiatry 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.4 5 He 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 ineffective, it was the bumbling and sometimes
humorous stepchild of modern science. But for a decade and more, research
psychiatrists have been working quietly in laboratories, 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
identifying 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 psychic 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." He 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 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
comprehension 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 198 4 and written by Nancy
Andreasen, future editor of the American journal of Psychiatry, it was touted
as "the first comprehensive account of the biomedical revolution in the
diagnosis and treatment of mental illness." In it, Andreasen concisely set
forth the tenets of biological psychiatry: "Th e major psychiatric
illnesses are diseases. They should be considered medical illnesses just as
diabetes, heart disease, and cancer are. The emphasis in this model is on
carefully diagnosing 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 researchers 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
knowledge 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," Andreasen explained.48
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 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 "partnership." The APA and
psychiatrists at academic medical centers served as the front men in this
arrangement, the public thereby seeing "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 197 4 when the
APA formed a task force to assess the importance of pharmaceutical support for
its future. The answer was "very," and in 198 0 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 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 sumptuous meal
and featured presentations by a "panel of experts." The speakers were
paid handsomely to give the talks, and the drug companies 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 observed, the companies were
"happy to cap them with free food and booze to sweeten the love of
learning." 5 1 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.5 2 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." 5 3 The APA
was prospering financially now, with its revenues jumping from $10. 5 million
in 198 0 to $21. 4 million 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 "independent." 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
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 $10,00 0 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 understanding of mental
disorders, and once they began serving as paid speakers, the pharmaceutical
companies sent money their way through multiple channels. As the New England
Journal of Medicine observed in 2000, thought leaders "serve as
consultants to companies whose products they are studying, join advisory boards
and speakers' bureaus, enter into patent and royalty arrangements, agree to be
the listed authors of articles ghostwritten by interested companies, promote
drugs and devices at company-sponsored symposiums, and allow themselves to be
plied with expensive gifts and trips to luxurious settings." 5 6 Nor was
it just a few psychiatrists from academia that pharma courted with its dollars.
The drug industry 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 Joh n Norto n confessed in a letter to
the New England Journal of Medicine that after he wrot e about the side effects
of the sponsor' s drug, "m y 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 wa s educating
physicians, and not being swayed by the sponsors."editorial on depression,
it "found very few who did not have financial 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 1980 s the
NIMH actively promoted the biological psychiatry story to the public, an effort
that took wing under the leadership 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
pharmaceutical firms, and soon Frazier was announcing that the NIMH, for the
first time in its forty-year history, would launch a major educational campaign
called the Depression Awareness, Recognition and Treatment (DART) program. This
educational effort would inform the public that depressive disorders are
"common, serious and treatable," the NIMH said. Pharmaceutical
companies would "contribute resources, knowledge and other forms of
assistance to the project," which the NIMH promised would run for at least
a decade.5 7 As it helped expand the market for psychiatric medications, the NIMH
even assured the public that the broken-brain story was true. "Two decades
of research have shown that [psychiatric 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.58
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 NAM I historian observed.5 9 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." 6 0 For the APA and pharma companies, the emergence of NAMI
could not have come at a more opportune moment. This was aparents' 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."6 1 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 199 0 letter.6 2 By that time, NAMI had more than 125,00 0 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 eighteen firms giving NAMI $11.7 2 million from
1996 to 1999. 64
In short, a powerful quartet of voices came together during
the 1980 s 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 intellectual legitimacy upon the
enterprise. The NIMH put the government's stamp of approval on the story. NAMI
provided a moral authority. This was a coalition that could convince American
society 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 1950 s and 1960s, and then, as we've seen in this
chapter, it was revived in the 1980s. However, the storytellers in the 1980’s 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 Broken 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
market. But fortunately for the proponents of biological psychiatry, criticism
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 published Dianetics: The Modern
Science of Mental Health, which outlined 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
huckster, and he in turn developed an intense hatred for psychiatry. In 1969,
Scientology and Thomas Szasz cofounded the Citizens Commission 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 Scientology's
protests, eager as they were to shove money to any organization 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 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." 6 5 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 presence 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.
14
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) 1
During the 1920s, owners of radios in the heartland of
America regularly tuned into station KFKB, which had perhaps the most powerful
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" sexual 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, stimulating 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 into Milford, each paying $75 0 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 distributed
to "publications interested in popularizing the latest developments 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 "Scientific Press" and reported a
"90 % to 95 % success rate" for his surgery, 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
Association 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 articles 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 customers. 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 psychiatry 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 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
serotonin 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 patients who completed
the four-week treatment showed distinct drug-induced improvement," Eli
Lilly's Ray Fuller tolcb his colleagues 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.4
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 benzodiazepines 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 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 licensing 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. 10
A German Eli Lilly employee 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 fluoxetine.*
It needed to hide the suicide data, and'in a 199 4 civil lawsuit, Nancy Lord,
an expert in clinical trial design, explained how the company did it. First, Eli
Lilly instructed investigators to record various 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 marke t fluoxetine in
Germany, but with a label that warned of the elevated risk of suicide.
entire testing process scientifically "worthless."
Yet even with these statistical manipulations, Eli Lilly still struggled to
present a convincing 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 documents, he discovered that imipramine
had proven to be more effective than fluoxetine in six of seven trials.1 4 The
FDA, in its March 28, 1985, review of one large trial, made the same
observation: "Imipramine was clearly more effective than placebo, whereas
fluoxetine was less consistently better than placebo." 1 5 At best,
fluoxetine's efficacy was of a very marginal sort, and FDA reviewer Richard
Kapit also worried about its safety. At least thirty-nine patients 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, dizziness, memory dysfunction, tremors, and impaired
motor coordination. Fluoxetine, Kapit concluded, "may negatively affect
patients with depression." 1 6 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 anecdotal 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 became 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.1 8 The FDA estimates that only 1 percent of
all adverse events are reported to MedWatch, which suggests that roughly 4
million Americans during that nine-year period had a bad or even fatal reaction
to Prozac.
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 marketplace. The public was not likely to embrace a
medication that German's licensing authority, in its initial review, had deemed
"totally 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."2 0 Next, John Feigner, from the University of California
at San Diego, reported that fluoxetine was at least equal in efficacy to
imipramine (and probably superior to the tricyclic) and that "no serious
side effects were observed" in his twenty-two fluoxetine patients during a
five-week study.2 1 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. 2 2
"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." 24
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 "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." 2 5
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
depression"—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 concentrations of
[serotonin metabolites] in their cerebrospinal fluid." A delusional belief
was now spreading through the medical literature, and perhaps not surprisingly,
the Kentucky psychiatrists concluded that fluoxetine, which theoretically
raised serotonin levels, was "an ideal drug for the treatment of
depression." 2 6
This trail of reports in medical journals provided Eli Lilly
with the sound bites it needed to advertise its drug to doctors. The company
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 approved, 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 DAR T
"public awareness" campaign turned out to be the perfect vehicle for
doing so.
After the NIMH announced its plans for DAR T 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 earlier, 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
intervention." 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 delivering a different
message.
The purpose of DART, the NIMH explained in 1988, was
"to change public attitudes so that there is greater acceptance of
depression 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 antidepressants produced recovery rates of "70 % to
80 % in comparison with 20 % to 40 % for placebo." The NIMH vowed to
continue DAR T indefinitely in order to "inform" the public of these
"facts." 27
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 NAM I had been on board
from the start. The NIMH ran advertisements in the media, and Eli Lilly helped
pay for the printing and distribution of 8 million DAR T brochures titled
"Depression: What You Need to Know." This pamphlet informed readers,
among other things, of the particular merits of "serotonergic" drugs
for the disease. "By making these materials on depressive illness
available, accessible in physicians' offices all over the country, important
information is effectively reaching the public in settings which 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 marketing
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, BY E
BLUES, the headline screamed, A NEW WONDER DRUG FO R 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
magazine 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 BREAKTHROUGH DRUG FO R
DEPRESSION the magazine announced. Physicians were now writing 650,00 0
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!" 3 0 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 balance of
neurotransmitter activity in the brain, correcting an abnormal 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."
3 1 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 chemical imbalance in the brain. To
correct it, the doctor prescribed Prozac." 32
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." 3 3 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 printing
plant where he had worked and opened fire with an AK-47 assault rifle, killing
eight and wounding twelve. The Citizens Commission 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
criticizing 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. 3 5 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." 3 6 The company ran
media-training sessions for the academic psychiatrists it hired as consultants,
getting them to practice their delivery of this message. "Frankly, I was
unimpressed with 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. 37
An article that appeared in the Wall Street Journal on April
19, 1991, showed that Eli Lilly's training sessions had paid off.
"Scientology," the paper informed its readers, was a
"quasi-religious/ business/paramilitary organization" that was
"waging war on psychiatry." The group had attacked Prozac's safety
even though "doctors 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 "demoralizing
revelation to watch twenty years of solid research by doctors and scientists
shouted down in twenty-second sound bites by Scientologists and lawyers."
Indeed, the Wall Street Journal reported, Eli Lilly, in response to concerns
about Prozac's safety, had asked "suicide 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
treatment." 38
Rosenbaum, naturally, was one of Eli Lilly's "outside
professionals." As the Boston Globe later reported, he "sat on a
marketing advisory panel for Lilly before Prozac was launched," his
relationship to Eli Lilly a "cozy" one. 3 9 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 legitimate 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
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 question. 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 position 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?
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 compound, 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 widespread medicating of the American mind was now under way,
and—as a very quick review will reveal—it was this same storytelling 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 psychiatric 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 committee" for the testing
process, and it paid Daniel Freedman, editor of the Archives of General
Psychiatry, to be an assistant to its "division of medical affairs."
4 3 This was just part of the company's efforts to co-opt academic psychiatry:
"Th e most senior psychiatrists in the world were flooded with offers of
consultancies" from Upjohn, said Isaac Marks, an expert in anxiety
disorders at the Institute of Psychiatry in London. 44
Klerman and Upjohn designed Upjohn's Cross National
Collaborative 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 alprazolam
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" reaction 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 significantly," 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 symptoms more severe than when the study
began, and an equal percentage 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, diarrhea,
decreased appetite, and weight loss. 47
The Xanax Study
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 at the end of the study were much
more symptomatic.
Source:
Ballenger, C. "Alprazolam in panic disorder and agoraphobia."
Archives of General Psychiatry 45 (1988): 413-22. Pecknold, C. "Alprazolam
in panic disorder and agoraphobia." Archives of General Psychiatry 45
(1988): 429-36.
In sum, at the end of fourteen weeks, the drug-exposed
patients were worse off than the placebo group: They were more phobic, 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 reviewed
the data could see the harm caused by alprazolam. But in order for Xanax to be
successfully marketed, Upjohn needed its investigators to draw a different sort
of conclusion, and so they did, 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 "alprazolam was found to be effective and well-tolerated." 4 8
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 regularly 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." 4 9 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
Institute of Psychiatry subsequently pointed out how transparently ridiculous
this all was. In a letter to the Archives of General Psychiatry, 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." 5 1 The entire affair, Marks subsequently
wrote, "is a classic demonstration 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 symposium at the APA's 1988 meeting where
the "expert panel" highlighted 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
Upjohn. Both Shervert Frazier and Gerald Klerman penned a "Dear
Doctor" letter that Upjohn included in the promotional literature it sent
to doctors about Xana x as a treatment for panic disorder. Upjohn also gave $1.
5 million to the APA so that it could mount a DART-like campaign to
"educate" psychiatrists, health-care workers, and the public about
panic disorder, which was said to be "under- recognized and
undertreated."5 3 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 TH E WAY, a St. Louis Post- Dispatch headline announced.
Treatment, the paper said, helped 70 to 90 percent of those with the
debilitating condition, which afflicted "4 million adults in this
country." 5 5 The Associated Press explained that "a biochemical
malfunctioning in the brain is believed to be one of the causes of panic
attacks. Xanax can block the attacks by interacting with several different
systems in the brain." 5 6 In the Chicago Sun-Times, Dr. John Zajecka at
Rush Medical College in Chicago announced that "Xana x is the fastest
acting and least toxic" of medications for the disorder.5 7 Once again, a
very effective, safe drug had arrived on the market, and in 1992, Xanax became the
fifth most frequently prescribed medication in the United States.5 8
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 employing 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 meaningful
comparison of the two drugs.5 9 In the FDA's letter of approval 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 presentation of data that conveys the
impression that risperidone is superior to haloperidol or any other marketed antipsychotic
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 "partnership" 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 schizophrenia
(psychosis) and superior to haloperidol in improving negative symptoms (lack of
emotion). The academic doctors reported that risperidone reduced hospital
stays, improved the patient's ability to function socially, and reduced
hostility. "Risperidone has important 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
investigators told of a wonder drug. This new agent, the Washington Post
reported, "represents a glimmer of hope for a disease that until recently
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 generation of antipsychotic
drugs." 6 2 The New York Times, quoting Richard Meibach, Janssen's
clinical research director, reported that "no major side effects" had
appeared in the two-thousand-plus patients 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. 6 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, provided
"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, dystonia, hypotension, constipation,
tachycardia, diabetes, seizures, leaking breasts, impotence, liver
abnormalities, and white blood cell disorders. Furthermore, warned the FDA's
Paul Leber, since olanzapine blocked receptors for many types of
neurotransmitters, "n o one should be surprised if, upon marketing, events
of all kinds and severity not previously identified are reported in association
with olanzapine's use." 6 4
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" manner 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.
agent that led to global improvement—it reduced positive
symptoms, caused fewer motor side effects than other antipsychotics, and
improved negative symptoms and cognitive function.6 5 This second atypical was
better than the first, and the Wall Street Journal ran with that angle.
Zyprexa, it announced, "has substantial advantages" 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." 6 6 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 atypical to market, Seroquel, the media settled on the notion that
collectively the new atypicals were a dramatic improvement over the older
drugs. They were, Parade told its readers, "far safer and more effective
in treating negative symptoms, such as difficulty in reasoning and speaking in
an organized way." 6 8 The newer drugs, the Chicago Tribune announced,
"are safer and more effective than older ones. They help people go to
work." 6 9 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." 7 0
NAMI chimed in, too, publishing a book titled Breakthroughs in Antipsychotic Medications, which helpfully explained that these new drugs "do a
better job of balancing all of the brain chemicals, including dopamine and
serotonin." 7 1 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 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 "breakthrough"
medications for schizophrenia. In this way, they rejuvenated 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 200 8 to provide a meaningful
clinical benefit only to severely depressed patients. Xana x is now understood
to be much more addictive than Valium, with various investigators determining
that two-thirds of people who take it for any length of time have trouble
getting off it. 7 3 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 patients were unable to stay on
the medications, mostly because of their "inefficacy or intolerable side
effects." 7 4 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. 7 5 All of this led two prominent psychiatrists to write in the
Lancet that the story of the atypicals as breakthrough medications 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 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 revolution 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
pharmaceutical companies brought new medications to market, they hired the top
psychiatrists in the country to tell of how these new wondrous 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 Harvard 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 I would be the youngest professor of
psychiatry in the history of Harvard Medical School. That was the trajectory I
was on." 7 7 However, he saw that the future belonged to biological
psychiatry, as opposed 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 198 7 on Oprah Winfrey'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 statements had
caused schizophrenia patients to stop taking their medications (and thus caused
harm). Although the commission decided not to take any action, it did conduct
an inquiry (rather than summarily 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
experienced was, in some ways, reminiscent of Mosher's fall from grace. During
the 1990s, he earned a reputation as one of the field's leading historians, his
writings focusing on the psychopharmacology era. He had served as secretary of
the British Association for Psychopharmacology, 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 completed a "healthy
volunteers" study. Two of the twenty volunteers 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 meeting 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. 7 8
In November of 2000, only a few months before he was
scheduled to start his new job at the University of Toronto, Healy gave a talk
on the history of psychopharmacology at a colloquium organized by the school.
In his presentation, Healy spoke about problems 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." 7 9
Although the audience subsequently rated his talk as the
colloquium'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 psychiatry, 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. 8 0 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
interview.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 California 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 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
problems 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 mischievous," said
Harvard Medical School psychiatrist Jerrold Rosenbaum, even though he was a
colleague of Glenmullen's. The press release naturally did not mention that
Rosenbaum was an Eli Lilly consultant.8 2 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 societal delusion about the merits of psychiatric drugs is easy to
document. 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) 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
continual 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 schizophrenia symptoms.
(University of Pennsylvania)
1998: In a World Health Organization study of the merits 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 outcomes
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 disability, versus 9 percent of those who didn't take the medication.
(Canadian investigators)
2001: In the pre-drug era, bipolar patients did not suffer
cognitive decline over the long term, but today they end up 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 scientists)
2005: Angel dust, amphetamines, and other drugs that induce
psychosis all increase D2 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, symptomatic nineteen weeks a
year, versus eleven weeks for those who didn't take any medication. (University
of Calgary)
2007: In a fifteen-year study, 40 percent of schizophrenia
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 significant marker not of
beneficial outcome, but of deterioration." 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 antidepressant. Those who took
an antidepressant were nearly four times as likely to become rapid cyclers,
which is associated with poor long-term outcome. (NIMH)
A check of newspaper archives reveals that the psychiatric
establishment 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 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 pharmaceutical 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 publicize 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 arguably the best study of the long-term outcomes of
schizophrenia patients that had ever been done in the United States. 8 3 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 stimulant 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 W H O study of better schizophrenia outcomes in poo r countries
where patients were not regularly maintained on the drugs, and since then, this
information has become somewha t known. In addition, I mentioned Marti n Harrow'
s fifteen-year schizophrenia study in a talk I gave at Hol y Cros s College in
February 2009, and that led to a February 8, 2009, article in the Worcester
Telegram and Gazette (Mass. ) that discussed Harrow' s work. Tha t was the
first time that news of his study had appeared in any American newspaper.
THE STORY THAT WAS AND WASN'T TOLD FOLLOWING ADH D 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
included a canned quote from lead author Peter Jensen stating that there was
still plenty of reason to keep children on Ritalin. "Ou r results 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 countries." 8 5 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 instance, the NIMH
website did not discuss the remarkable decline in bipolar outcomes in modern
times, even though Carlos Zarate, who coauthored the 200 0 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
schizophrenic children to be optimistic. Forty percent of those off medications
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. Antipsychotics, it informs the public, "correct
an imbalance in the chemicals that enable brain cells to communicate with each
other." 86
Finally, the entire outcomes history documented in this book
is missing from the 200 8 edition of the APA's Textbook of Psychiatry, which
means that medical students training to be psychiatrists are kept in the dark
about this history.8 7 The book does not discuss "supersensitivity
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
familiar with many of the sixteen studies listed above, but, if they do mention
them, they don't discuss the relevant facts about medication 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 treatment." 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 exaggerate 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.
15
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 CARLA T (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 distance, 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
Parkinsonian symptoms. As we sat outside a cafe, Jenna told me her story,
although 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 bringing the pastry to her lips.
"I' m sooooooo messed up," she says.
I had gone to the interview thinking that Jenna had been
diagnosed with tardive dyskinesia, an antipsychotic side effect that can
disable people. But it wasn't clear whether her motor impairments.
Although Jenn a said that I could use her last name, her mother
an d stepfather, WHO have legal guardianship, requested that I use her first
nam e only.
were due to that particular type of drug-induced dysfunction
or to a more idiosyncratic drug-related process, and by the time the interview
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 dictated 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
normal," her mother recalled.
When Jenna entered ninth grade, her mother and stepfather
decided 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 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
hospital. 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 herself,
and thus the medications haven't been much help in that regard, 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 details 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 calculated that even if
generics were prescribed whenever possible, she was consuming $80 0 of
medication monthly, or roughly $10,00 0 annually. She had been on psychiatric
medications for twelve years, which meant that her Rx bill for psychiatric
medications might already 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."
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 1970 s psychiatry was
worried about its survival. The public viewed its therapies as "low in
efficacy," 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 storytelling 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 DAR T campaign informed
the public that depression regularly went "undiagnosed and
untreated." 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
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 efforts. NAMI, for its
part, understood that its "educational" efforts served a commercial
end, writing in a 200 0 document filed with the government that
"providers, health plans, and pharmaceutical companies want to grow their
markets and to increase their share of the market.... NAM I 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 society, and DSM-IV, an 886-page tome published in 1994, listed 29 7
disorders, 32 more than DSM-III. New and expanded diagnoses invite 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 illness, 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" campaigns. Abbott Laboratories and
NAM I teamed up to promote a "Bipolar Awareness Day"; in 2002, Eli
Lilly joined with the De-
pression and Bipolar Support Alliance to launch a new online
destination, 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 psychotropics
step by step. First, in the 1980s, the prescribing of stimulants 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 medications 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. 4 The New
York Times, in its coverage of this initiative, explained quite clearly what
was driving it: "The adult market for [SSRIs] has become saturated.... The
companies are looking for expanded markets." 5 Psychiatry quickly provided
a medical cover for this marketing effort, with the American Academy of Child
and Adolescent Psychiatry announcing that 5 percent of all children in the
United States were clinically depressed. "Man y of these young patients
now are inadequately treated, experts say, often leading to long-term emotional
and behavioral problems, drug abuse, or even suicide," the Wall Street
Journal reported.6
The creation of the "juvenile bipolar" market was
a bit more complicated. Prior to the 1990s, psychiatry thought that bipolar
illness simply didn't occur in prepubertal children, or was extremely rare. But
children and teenagers prescribed stimulants and antidepressants 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.
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 problems
should instead be diagnosed with juvenile bipolar illness. "Th e
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 199 6 that many children diagnosed with ADH
D 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.* 9 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 indefinitely, 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 multiple 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 Harvar d Medical School. "Full
professor," he replied. "What' s above that? " the attorney
asked. "God, " Biederman replied.
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; psychiatrists 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 psychiatrists
that Zyprexa "is a great mood stabilizer, especially for patients whose
symptoms were aggravated by an SSRI." 1 0 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 everywhere, and then this new group of patients provided a market
for the atypicals.*
All of this has produced a growth industry of impressive
dimensions. 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 severely ill patients—were the
top revenue-producing class of drugs in 2008, ahead even of the
cholesterol-lowering agents. 1 2 Total sales of all psychotropic drugs in 200 8
topped $40 billion. Today—and this In a similar vein, pharmaceutical companies
have pounced on the fact that man y of the drugs initially prescribed for a
target sympto m don' t work very well. "Tw o out of three people treated
for depression still have symptoms, " a Bristol-Myers Squibb commercia l
informed television viewers in 2009. The solution? Add an atypical
antipsychotic, Abilify, to the mix.
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 personal wealth for executives at pharmaceutical companies, and money
also flows in fairly copious amounts to the academic psychiatrists 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 involved, 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 antibiotic, 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 market, 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 $1 0 billion to $90 billion. An investor who bought
$10,00 0 of Eli Lilly stock in 1987 would have seen that investment grow to
$96,85 0 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 to their salaries and bonuses, netted around $3.1 billion from the
stock options they exercised.14
Academic psychiatrists
The pharmaceutical
companies would not have been able to build a $40 billion market for
psychiatric drugs without the help of psychiatrists 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
companies, in their internal memos, accurately call these psychiatrists
"key opinion leaders," or KOLs for short.
Thanks to a 200 8 investigation by Iowa senator Charles
Grass- ley, the public got a glimpse of the amount of money that the
pharmaceutical 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 pharmaceutical companies, with the
medical schools expected to manage the "conflict of interest"
whenever this amount exceeds $10,00 0 annually. Grassley investigated the
records of twenty or so academic psychiatrists, and he found that not only were
many making much more than $10,00 0 a year, they were also hiding this fact
from their schools.
Here are a few examples of the money paid to KOLs in
psychiatry.
From
200 0 to 2007, Charles Nemeroff, chair of the psychiatry department at Emory Medical
School, earned at least $2. 8 million as a speaker and consultant for drug
firms, with GlaxoSmithKline alone paying him $960,00 0 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 medications, 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 Neuropsychopharmacology. In December of 2008, he resigned as chair of Emory's psychiatry
department, as he had failed to inform Emory of his drug-company paychecks.1 5
Zachary Stowe, also a professor of psychiatry at Emory, received $250,00 0 from
GlaxoSmithKline in 200 7 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 200 0 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 authoritative 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 GlaxoSmithKline 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 200 0 to 2005, Karen Wagner, director of child and
adolescent psychiatry at the University of Texas, collected more than $160,00 0
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,
GlaxoSmithKline concluded that in the study, Paxil "failed to demonstrate
a statistically significant difference from placebo on the primary efficacy
measures." 1 8 In addition, five of the ninety-three adolescents treated
with Paxil in the study
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 200 1 article published in the Journal of the American Academy of
Child & Adolescent Psychiatry, Wagner and twenty-one other leading child
psychiatrists stated that the study proved that Paxil is "generally well
tolerated and effective for major depression in adolescents." 1 9 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 "headache." New York State attorney general Eliot
Spitzer sued GlaxoSmithKline for fraudulently marketing Paxil to adolescents, a
case which was settled out of court.
All told, Wagner has been a consultant or advisor to at
least seventeen pharmaceutical companies. The $160,00 0 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
Massachusetts General Hospital in Boston, collected more than
$750,00 0 from Forest Laboratories to promote the
prescribing of Celexa and Lexapro to children and adolescents. He gave more
than 35 0 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!" 2 1 In March of 2009, the federal government charged Forest with
illegally marketing 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 200 3 to 2007, Melissa DelBello, an associate professor
of psychiatry at the University of Cincinnati, received at
least
$418,00 0 from AstraZeneca. She promoted the prescribing
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.2 2
Joseph Biederman may have been the KO L 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 200 0 to 2007, with much
of this money coming from Janssen, the division of Johnson &c Johnson that
sells Risperdal.2 3
Biederman also got the company to pay $2 million from 200 2
to 200 5 to create the Johnson &C Johnson Center for Pediatric
Psychopathology at Massachusetts General Hospital. 2 4 In a 200 2 report on the
center, he candidly set forth its aims. The center, he explained, was a
"strategic collaboration" 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 CM E (continuing medical
education) courses to train pediatricians and psychiatrists 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 addition, the center would promote the understanding that "pediatric
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."* 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 chronically ill in the wa y he
describes. But there is no medical literature showing that there is a disease
that takes this course in unmedicated children.
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 diagnosis. 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 company cabinet that estimates the
expected lifetime consumption 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 "influence" 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 dinners or to
other physicians in their offices. Pay typically starts at
$75 0 per event and rises from there. Two states, Minnesota
and Vermont, have passed "sunshine" laws that disclose these
payments, 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 200 2 to 2006, the
recipients of drug-company money included seven past presidents of the
Minnesota Psychiatric Society and seventeen faculty psychiatrists at the
University of Minnesota. John Simon, who was a member of the state's Medicaid
formulary committee, which guides the state's spending on drugs, was the
top-paid psychiatrist, earning $570,00 0 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 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 regularly come to
their offices bearing small gifts. "Gave Dr. Child a cupcake sized peanut
butter cup," wrote an Eli Lilly sales representative, in a 200 2 report to
her boss. "H e was kind of tickled." Or as she said after another
sales call: "Do c and staff loved the goodie box I brought in, filled with
useful items for their new clinic." 2 7 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 $2,50 0 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 "philanthropy" grants it makes, and this
provides a peek at the money going to patient advocacy groups and various
educational organizations. In the first quarter of 200 9 alone, Eli Lilly gave
$551,00 0 to NAMI and its local chapters, $465,00 0 to the National Mental
Health Association, $130,00 0 to CHAD D (an ADHD patient- advocacy group), and
$69,25 0 to the American Foundation for Suicide Prevention. The company gave
more than $1 million to various educational organizations, including $279,53 3
to the Antidote Education Company, which runs a "continuing medical
education" course. Those are the amounts from one pharmaceutical company
for three months; any full accounting of the flow of money
to patient advocacy groups and educational organizations would require adding
up the grants from all of the makers of psychiatric drugs. 2 8
We All Pay the Tab
According to a 200 9 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.2 9 In 2008, the
United States spent about $17 0 billion on mental health services, which is
twice the amount it spent in 2001, and this spending is projected to increase
to $28 0 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 generates
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 society. 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
16
Blueprints for Reform
I think it is time for another hunger strike."
— VINC E BOEHM,
200 9
On July 28, 2003, six "psychiatric survivors"
associated with MindFreedom International, a patients' rights organization,
announced 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 "scientifically 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 unable 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
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
survivors" 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 acknowledged the same bottom
line. "The precise causes [etiology] of mental 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
MindFreedom group broke their fast (several started to have health problems),
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 conditions that can be diagnosed
accurately and treated effectively."4 But it was clear to all observers
who had won this battle. The strikers 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 disease" 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
officials reading this exchange to ask for straightforward answers to our
questions from the APA. We also ask Congress to investigate the mass deception
that the "diagnosis and treatment 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.
"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 bullying 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 selective,
cautious manner (or not at all), and are producing good results. 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 psychiatric establishment to think about the
medications in a scientifically honest way and to speak honestly about them to
the public. Psychiatry would have to acknowledge that the biological causes of
mental 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 medications 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 alternative therapies that don't rely on the
medications or at least minimize their use.
In his 199 2 book How to Become a Schizophrenic, John
Modrow—who had been so diagnosed—wrote the following: "Ho w then are we to
help 'schizophrenics'? The answer is simple:
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
investigations 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 perceived 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 published 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 establishment. "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
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 240,00 0 in the area, and whereas all the seriously
mentally were treated at the North Wales Asylum in Denbigh a century ago, today
all psychiatric patients needing to be hospitalized 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 189 4 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 succumb to tuberculosis or some
other infectious disease, they regularly 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 patients. 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 admitted to the Denbigh asylum a century
earlier. Seventy-six percent of the 52 2 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 1990 s 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 modern treatments apparently having set up a
"revolving door." 9
"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
judiciously. 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 70,00 0 people who
live there, and during the 1970 s 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
chronically ill. But today the long-term outcomes of
psychotic patients 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 196 9 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 psychiatrists in the country
thought that psychotherapy could help schizophrenics. 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 anyone
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 important, 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
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 integrated
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 1970 s 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 198 4 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
Schizophrenia 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 indeed 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 experimental 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
without medication. They become more interactive. They become themselves."
Added Aaltonen: "If you can postpone medication, that's important."
It might seem that Finnish psychiatry, given the outcomes of
the study, would have then embraced—on a national level—this "n o
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 "biologically" oriented.
Even in Turku, first-episode patients are regularly 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 documenting the extraordinary
outcomes of psychotic patients in western Lapland.
The transformation of care at Keropudas Hospital, from a system
in which patients were regularly hospitalized and medicated to one in which
patients are infrequently hospitalized and only occasionally 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
conventional psychotherapy. "The language we use when the patient is
sitting 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 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 1992-9 3 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 proceeds 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 199 2 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 of the patients had never been exposed to antipsychotic
medication, and only 20 percent took the drugs regularly.1 3 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.
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 |
7% |
|
On disability |
20% |
Source: Seikkula, J. "Five-year experience o f
first-episode nonaffective psychosis in open-dialogue approach. "
Psychotherapy Research 16 (2006): 214-28.
"I am confident of this idea," Seikkula said.
"There are patients who may be living in a quite peculiar way, and they
may have psychotic 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 (psychiatrists, psychologists,
nurses, and social workers), and most have completed a nine-hundred-hour,
three-year course in family therapy. 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 social
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." 1 4
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 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 therapists 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 conversation."
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 medication
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 medication."
From the outset, the therapists strive to give both the
patient and family a sense of hope. "Th e 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
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
patient and family, and as this process unfolds, teachers and prospective
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
transformed "the picture of the psychotic population" in western
Lapland. Since the 1992-9 3 study, not a single first-episode psychotic patient
has ended up chronically hospitalized. Spending on psychiatric services in the
region dropped 33 percent from the 1980 s 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 200 2 to
2006, Tornio participated 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 become so comfortable with this
gentle form of care that they call the hospital (or one of the outpatient
clinics) at the first sign of psychosis 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. 1 5
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. 1 6 "This really happened," Seikkula said. "It's
not just a theory."
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 selective 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 conversation 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. "Th e severe symptoms 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 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 "antidepressants are not
recommended for the initial treament of mild depression, 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 depression 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. 2
0 In addition, over time, exercise produces a multitude of "side
benefits." It enhances cardiovascular function, increases muscle strength,
lowers blood pressure, and improves cognitive function. People sleep better,
they function better sexually, and they also tend to become more socially
engaged.
The Long-Term Benefit of Exercise for Depression
Treatment During First Four Month s |
Percentage o f Patient s in Remission at End of Four
Month s |
Percentage of Remitted Patient s WHO Relapsed in
Six-Mont h Follow-up |
Percentage o f Patients Depressed at End of Ten
Months |
Zoloft alone |
69 % |
38 % |
52 % |
Zoloft plus exercise therapy |
66 % |
31 % |
55 % |
Exercise therapy alone |
60 % |
8 % |
30 % |
In this stud y by Duke researchers, olde r patients with depression
n were e treated d for 16 weeks in
one of three ways, an d then followed for another six
months. Patients treated with exercise alone had the lowest rates of relapse
during the following six months, an d a s a group, the y were much less likely
t e suffering from depressive symptoms at the end
often months. Source: Babyak,
M. "Exercise treatment for major depression. "
Psychosomatic Medicine 62 (2000): 633-38.100-11.
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.2 1 Blumenthal then
tracked the patients for another six months, with the patients free to choose
whatever treatment they wanted during this period, and at the end the patients
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" patients, which suggested
that exposure to Zoloft negated the benefits of exercise. "This was an
unexpected finding, because it was assumed that combining exercise with
medication would have, if anything, an additive effect," Blumenthal wrote.
2 2
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 recreational 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.
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
collaborating YMC A 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 programs may involve
group walks, outdoor stretching classes, and volunteer environmental work
(managing local woodlands, improving 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
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 $15,00 0 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
children 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 headphones was singing
a cappella (and quite well), and the girl huddled over the photo album had
started calling me Bob Marley, apparently 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. "I'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 services 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
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 198 7 to oversee the
children'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 emotional 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 children weren't medicated, and he saw a
number of them become attached 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 connection
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 happened 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 seriously 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,' "
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 engage 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 children
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 responsible 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."
"They come in thinking, 'I'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 amazing 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 ordinary
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: 22
5 children lived at its residences 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
direction. And yet, it is difficult to be optimistic that their lives continue
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
drugs," he said, and then he began telling us about
migratory turtles, 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, including one who needed to take drugs to
keep from going mad. Steve held center stage for at least an hour, and
afterward he happily informed 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, uncooperative, 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 Takeesha 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 suddenly 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 imaginary 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-
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
timeout 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, "Bo b 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
treatments 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 normal amounts of the neurotransmitter? Do
receptor densities return 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 2009, a major provider of
mental-health services in eastern and central Massachusetts, Advocates, drew up
a plan for a medication-withdrawal study. Advocates provides services 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." 2 4
The medical director of Advocates, Chris Gordon, who is an
assistant clinical professor of psychiatry at Harvard Medical School, said that
he hoped to obtain funding from either the state Department 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
medications. 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
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 1980 s because of bouts of mania, and that personal
experience has inspired a lifelong career of fighting to improve the plight of
the mentally ill in our society.
During the 1980 s 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 legislature 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.2 6 The
state gave $20 0 million and nearly a million acres of land to a newly created
Mental Health Trust Authority, 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
information" campaign. PsychRights brought various people to Anchorage to
speak to judges, lawyers, psychiatrists, and the general public about the outcomes
literature for antipsychotics.* Gottstein believed 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.
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 support
alternatives, right?"
State case laws governing the forced treatment of
psychiatric patients date back to the late 1970s. Although state supreme courts
typically ruled that patients have a right to refuse treatment (in nonemergency
situations), they nevertheless noted that antipsychotics were understood to be
"a medically sound treatment of mental disease," and thus hospitals
could apply to a court to sanction forced treatment. At such hearings,
hospitals regularly argue that no competent person would refuse "medically
sound treatment," and thus courts consistently order patients to be
medicated.2 7 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 psychiatrist who
knows the outcomes literature well, Grace Jackson, to serve as his expert
witnesses, and he also filed copies of the many research 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 effects." As such, it
ruled in Myers v. Alaska Psychiatric Institute that a psychiatric patient could
be forcibly medicated only if a court "expressly 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." 2 8 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
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
psychiatric 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 expectation 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." 2 9
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 Brown 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 previously 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."
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 disabling 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 scientific
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
psychiatric 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 illness. One in every fifteen young adults (eighteen to twenty-six
years old) is "functionally impaired" by mental illness. Some 25 0
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 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 prescribe the medications in a much
more limited, cautious manner. We would stop putting foster children on
heavy-duty cocktails and pretending 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.
— EDWI N PERC Y WHIPPL E (1866)'
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 disabling
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 believes, 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 Harvard 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 antipsychotics to
a few of his colleagues. Now, Seikkula and others at Keropudas Hospital in
Tornio did not decide to use antipsychotics 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 antidepressants, too. He and others had
been researching the long-term outcomes 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?
N O T E S
To read many of the source documents listed here, go to
madinamerica.com or robertwhitaker.org
Chapter 1: A Modern Plague
J. Bronowski, The Ascent of Man (New York: Little, Brown
& Co., 1973), 153.
IMS Health, "200 7 top therapeutic classes by U.S.
sales."
U.S. Department of Health and Human Services, Mental Health:
A Report of the Surgeon General (1999), 3, 68, 78.
E. Shorter, A History of Psychiatry (New York: John Wiley
& Sons, 1997), 255.
R. Friedman, "On the Horizon, Personalized Depression
Drugs," New York Times,
June 19, 2007.
Boston Globe editorial, "When Kids Need Meds,"
June 22, 2007.
Address by Carolyn Robinowitz, APA Annual Conference,
Washington, D.C., May 4, 2008.
C. Silverman, The Epidemiology of Depression (Baltimore:
Johns Hopkins Press, 1968), 139.
Social Security Administration, annual statistical reports
on the SSDI and SSI programs, 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 adjusted 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 recipients) = total number of disabled
mentally ill.
Silverman, The Epidemiology of Depression, 139.
The annual Social Security Administration reports don't
provide data on the specific
diagnoses of SSI and SSDI recipients disabled by mental
illness. However, various researchers 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 clinical trials study of
employment models for mental health consumers," available at: psych.uic.edu/EIDP/eidp-3-20-03.pdf.
U.S. Government Accountability Office, "Young adults
with serious mental illness" (June 2008).
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
J. Young, The Medical Messiahs (Princeton, NJ: Princeton
University Press, 1967), 281.
Chemical Heritage Foundation, "Paul Ehrlich, Pharmaceutical
Achiever," accessed at chemheritage.org.
P. de Kruif, Dr. Ehrlich's Magic Bullet (New York: Pocket
Books, 1940), 387.
L. Sutherland, Magic Bullets (Boston: Little, Brown and
Company, 1956), 127.
L. Garrett, The Coming Plague (New York: Penguin, 1995), 49.
T. Mahoney, The Merchants of Life (New York: Harper &c
Brothers, 1959), 14.
"Mind Is Mapped in Cure of Insane," New York
Times, May 15, 1937.
"Surgery Used on the Soul-Sick," New York Times,
June 7, 1937.
A. Deutsch, The Shame of the States (New York: Harcourt
Brace, 1948), 41.
E. Torrey, The Invisible Plague (New Brunswick, NJ: Rutgers
University Press, 2001), 295.
G. Grob, The Mad Among Us (Cambridge, MA: Harvard University
Press, 1994), 189.
"Need for Public Education on Psychiatry Is Stressed,"
New York Times, November 16, 1947.
Chapter 4: Psychiatry's Magic Bullets
E. Valenstein, Blaming the Brain (New York: The Free Press,
1998), 38.
J. Swazey, Chlorpromazine in Psychiatry (Cambridge, MA: MIT
Press, 1974), 78.
Ibid, 79. 4. Ibid, 105.
5. Ibid, 134-35.
F. Ayd Jr., Discoveries in Biological Psychiatry
(Philadelphia: Lippincott, 1970), 160.
Symposium proceedings, Chlorpromazine and Mental Health
(Philadelphia: Lea and Fabiger, 1955), 132.
Ayd, Discoveries in Biological Psychiatry, 121.
M. Smith, Small Comfort (New York: Praeger, 1985), 23.
Ibid, 26.
Ibid, 72.
"TB and Hope," Time, March 3, 1952.
Valenstein, Blaming the Brain, 38.
"TB Drug Is Tried in Mental Cases," New York
Times, April 7, 1957.
M. Mintz, The Therapeutic Nightmare (Boston: Houghton
Mifflin, 1965), 166.
16. Ibid, 488.
17. Ibid, 481. 18. Ibid, 59, 62.
T. Mahoney, The Merchants of Life (New York: Harper 8c
Brothers, 1959), 4, 16.
Mintz, The Therapeutic Nightmare, 83.
Swazey, Chlorpromazine in Psychiatry, 190.
"Wonder Drug of 1954?" Time, June 14, 1954.
"Pills for the Mind," Time, March 7, 1955.
"Wonder Drugs: New Cures for Mental Ills?" U.S.
News and World Report, June
17, 1955.
"Pills for the Mind," Time, March 7, 1955.
"Don't-Give-a-Damn Pills," Time, February 27,
1956.
Smith, Small Comfort, 67-69.
"To Nirvana with Miltown," Time, July 7, 1958.
"Wonder Drug of 1954?" Time, June 14, 1954.
"TB Drug Is Tried in Mental Cases," New York
Times, April 7, 1957.
Smith, Small Comfort, 70.
"Science Notes: Mental Drug Shows Promise," New
York Times, April 7, 1957.
"Drugs and Depression," New York Times, September
6, 1959.
H. Himwich, "Psychopharmacologic drugs," Science
127 (1958): 59-72.
Smith, Small Comfort, 110.
36. Ibid, 104.
The NIMH Psychopharmacology Service Center Collaborative
Study Group, "Phe- nothiazine treatment in acute schizophrenia,"
Archives of General Psychiatry 10 (1964): 246-61.
Valenstein, Blaming the Brain, 70-79. Also see David Healy,
The Creation of Psychopharmacology (Cambridge, MA: Harvard University Press,
2002), 106, 205- 206.
J. Schildkraut, "The catecholamine hypothesis of
affective disorders," American Journal of Psychiatry 111 (1965): 509-22.
Valenstein, Blaming the Brain, 82.
A. Baumeister, "Historical development of the dopamine hypothesis
of schizophrenia," Journal of the History of the Neurosciences 11 (2002):
265-77.
Swazey, Chlorpromazine in Psychiatry, 4.
Ibid, 8.
Ayd, Discoveries in Biological Psychiatry, 215-16.
45. Ibid, 127.
46. Ibid, 195.
Chapter 5: The Hunt for Chemical Imbalances
T. H. Huxley, Critiques and Addresses (London: Macmillan
&c Co., 1873), 229.
E. Azmitia, "Awakening the sleeping giant,"
Journal of Clinical Psychiatry 52
(1991), suppl. 12:4-16.
M. Bowers, "Cerebrospinal fluid 5-hydroxyindoleacetic
acid and homovanillic acid in psychiatric patients," International Journal
of Neuropharmacology 8 (1969): 255-62.
R. Papeschi, "Homovanillic and 5-hydroxyindoleacetic
acid in cerebrospinal fluid of depressed patients," Archives of General
Psychiatry 25 (1971): 354-58.
M. Bowers, "Lumbar CSF 5-hydroxyindoleacetic acid and
homovanillic acid in affective syndromes," Journal of Nervous and Mental
Disease 158 (1974): 325-30.
D. L. Davies, "Reserpine in the treatment of anxious
and depressed patients,"
Lancet 2 (1955): 117-20.
J. Mendels, "Brain biogenic amine depletion and
mood," Archives of General Psychiatry 30 (1974): 447-51.
M. Asberg, "Serotonin depression: A biochemical
subgroup within the affective disorders?" Science 191 (1976): 478-80 ; M.
Asberg, "5-HIAA in the cerebrospinal fluid," Archives of General Psychiatry
33 (1976): 1193-97.
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 Biochemistry and Behavior 25 (1986): 805-11.
J. Maas, "Pretreatment neurotransmitter metabolite
levels and response to tricyclic antidepressant drugs," American Journal
of Psychiatry 141 (1984): 1159-71.
J. Lacasse, "Serotonin and depression: a disconnect
between the advertisements and the scientific literature," PloS Medicine 2
(2005): 1211-16.
C. Ross, Pseudoscience in Biological Psychiatry (New York:
John Wiley &c Sons, 1995), 111.
. Lacasse, "Serotonin and depression."
D. Healy, "Ads for SSRI antidepressants are
misleading," PloS Medicine news release, November 2005.
I. Creese, "Dopamine receptor binding predicts clinical
and pharmacological potencies of antischizophrenic drugs," Science 192
(1976): 481-83 ; P. Seeman, "Antipsychotic drug doses and
neuroleptic/dopamine receptors," Nature 261 (1976J: 177-79.
"Schizophrenia: Vast effort focuses on four
areas," New York Times, November 13, 1979.
M. Bowers, "Central dopamine turnover in schizophrenic
syndromes," Archives of General Psychiatry 31 (1974): 50-54.
R. Post, "Cerebrospinal fluid amine metabolites in
acute schizophrenia," Archives of General Psychiatry 32 (1975): 1063-68.
J. Haracz, "The dopamine hypothesis: an overview of
studies with schizophrenic patients," Schizophrenia Bulletin 8 (1982):
438-58.
. T. Lee, "Binding of 3H-neuroleptics and 3
H-apomorphine in schizophrenic brains,"
Nature 374 (1978): 897-900.
. D. Burt, "Antischizophrenic drugs: chronic treatment
elevates dopamine receptor binding in brain," Science 196 (1977): 326-27.
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.
. A. MacKay, "Increased brain dopamine and dopamine
receptors in schizophrenia,"
Archives of General Psychiatry 39 (1982): 991-97.
J. Kornhuber, "3 H-spiperone binding sites in
post-mortem brains from schizophrenic patients," Journal of Neural Transmission
75 (1989): 1-10.
. J. Martinot, "Striatal D2 dopaminergic receptors
assessed with positron emission tomography and bromospiperone in untreated
schizophrenic patients," American 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 D2 dopamine receptor characteristics in neuroleptic- nai've
schizophrenic patients studied with positron emission tomography," Archives
of General Psychiatry 51 (1994): 116-23.
. 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.
J. Kane, "Towards more effective antipsychotic
treatment," British Journal of Psychiatry 165, suppl. 25 (1994): 22-31.
. E. Nestler and S. Hyman, Molecular Neuropharmacology (New
York: McGraw Hill, 2002), 392.
. J. Mendels, "Brain biogenic amine depletion and
mood," Archives of General Psychiatry 30 (1974): 447-51.
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.
. D. Healy, The Creation of Psychopharmacology (Cambridge,
MA: Harvard University Press, 2002), 217.
E. Valenstein, Blaming the Brain (New York: The Free Press,
1998), 96.
. U.S. Department of Health and Human Services, Mental
Health: A Report of the Surgeon General (1999), 3, 68, 78.
J. Glenmullen, Prozac Backlash (New York: Simon &
Schuster, 2000), 196.
Lacasse, "Serotonin and depression."
R. Fuller, "Effect of an uptake inhibitor on serotonin
metabolism in rat brain," Life Sciences 15 (1974): 1161-71.
D. Wong, "Subsensitivity of serotonin receptors after
long-term treatment of rats with fluoxetine," Research Communications in
Chemical Pathology and Pharmacology 32 (1981): 41-51.
J. Wamsley, "Receptor alterations associated with
serotonergic agents," Journal of Clinical Psychiatry 48, suppl. (1987):
19-25.
. A. Schatzberg, Textbook of Psychopharmacology (Washington,
DC: American Psychiatric Press, 1995), 8.
. C. Montigny, "Modification of serotonergic neuron
properties by long-term treatment 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 Pharmacology 32 (1981): 41-51.
. C. Montigny, "Modification of serotonergic neuron
properties by long-term treatment with serotonin reuptake blockers,"
Journal of Clinical Psychiatry 51, suppl. B (1990): 4-8.
. R. Fuller, "Inhibition of serotonin reuptake,"
Federation Proceedings 36 (1977): 2154-58.
. B. Jacobs, "Serotonin and behavior," Journal of
Clinical Psychiatry 52, suppl. (1991): 151-62.
. Schatzberg, Textbook of Psychopharmacology, 619.
. 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
E. Stip, "Happy birthday neuroleptics!" European
Psychiatry 17 (2002): 115-19.
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).
P. Popenoe, "In the melting pot," Journal of
Heredity 14 (1923): 223.
J. Cole, editor, Psychopharmacology (Washington, DC:
National Academy of Sciences, 1959), 142.
5. Ibid, 386-87.
N. Lehrman, "Follow-up of brief and prolonged
psychiatric hospitalization," Comprehensive Psychiatry 2 (1961): 227-40.
R. Warner, Recovery from Schizophrenia (Boston: Routledge
& Kegan Paul, 1985), 74.
L. Epstein, "An approach to the effect of ataraxic
drugs on hospital release rates,"
American Journal of Psychiatry 119 (1962): 246-61.
C. Silverman, The Epidemiology of Depression (Baltimore:
Johns Hopkins Press, 1968), 139.
J. Swazey, Chlorpromazine in Psychiatry (Cambridge, MA: MIT
Press, 1974), 247.
Cole, Psychopharmacology, 144,285.
12. Ibid, 285.
13. Ibid, 347.
R. Baldessarini, Chemotherapy in Psychiatry (Cambridge, MA:
Harvard University Press, 1977), 29.
A. Schatzberg, editor, Textbook of Psychopharmacology
(Washington, DC: American Psychiatric Press, 1995), 624.
P. Gilbert, "Neuroleptic withdrawal in schizophrenic
patients," Archives of General Psychiatry 52 (1995): 173-88.
J. Geddes, "Prevention of relapse," New England
Journal of Medicine 346 (2002): 56-58.
L. Dixon, "Conventional antipsychotic medications for
schizophrenia." Schizophrenia Bulletin 21 (1995): 567-77.
Stip, "Happy birthday, neuroleptics!"
. N. Schooler, "One year after discharge,"
American journal of Psychiatry 123 (1967): 986-95.
. R. Prien, "Discontinuation of chemotherapy for
chronic schizophrenics," Hospital and Community Psychiatry 22 (1971):
20-23.
. G. Gardos and J. Cole, "Maintenance antipsychotic
therapy: is the cure worse than the disease?" American journal of
Psychiatry 133 (1977): 32-36.
. 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."
J. Bockoven, "Comparison of two five-year follow-up
studies," American Journal of Psychiatry 132 (1975): 796-801.
. W. Carpenter, "The treatment of acute schizophrenia
without drugs," American Journal of Psychiatry 134 (1977): 14-20.
. M. Rappaport, "Are there schizophrenics for whom
drugs may be unnecessary or contraindicated?" International
Pharmacopsychiatry 13 (1978): 100-11.
S. Mathews, "A non-neuroleptic treatment for
schizophrenia," Schizophrenia Bulletin 5 (1979): 322-32.
. J. Bola, "Treatment of acute psychosis without
neuroleptics," Journal of Nervous and Mental Disease 191 (2003): 219-29.
. Carpenter, "The treatment of acute
schizophrenia."
G. Paul, "Maintenance psychotropic drugs in the
presence of active treatment programs," Archives of General Psychiatry 27
(1972): 106-14.
T. Van Putten, "The board and care home: does it
deserve a bad press?" Hospital and Community Psychiatry 30 (1979): 461-64.
Gardos and Cole, "Maintenance antipsychotic
therapy."
. P. Deniker, "Are the antipsychotic drugs to be withdrawn?"
in C. Shagass, editor,
Biological Psychiatry (New York: Elsevier, 1986), 1-9.
G. Chouinard, "Neuroleptic-induced supersensitivity
psychosis," American Journal of Psychiatry 135 (1978): 1409-10.
. G. Chouinard, "Neuroleptic-induced supersensitivity
psychosis: Clinical and pharmacologic characteristics," American Journal
of Psychiatry 137 (1980): 16-20.
G. Chouinard, "Neuroleptic-induced supersensitivity
psychosis, the 'Hump Course,' and tardive dyskinesia," Journal of Clinical
Psychopharmacology 2 (1982): 143-44.
G. Chouinard, "Severe cases of neuroleptic-induced
supersensitivity psychosis,"
Schizophrenia Research 5 (1991): 21-33.
P. Muller, "Dopaminergic supersensitivity after
neuroleptics," Psychopharmacology
60 (1978): 1-11.
. 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.
. P. Breggin, Brain Disabling Treatments in Psychiatry (New
York: Springer Publishing Company, 1997), 60.
. S. Snyder, Drugs and the Brain (New York: Scientific
American Library, 1986), 88.
. C. Harding, "The Vermont longitudinal study of
persons with severe mental illness," 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.
. P. McGuire, "New hope for people with
schizophrenia," APA Monitor 31 (February 2000).
. C. Harding, "Empirical correction of seven myths
about schizophrenia with implications for treatment," Acta Psychiatrica
Scandinavica 384, suppl. (1994): 14-16.
. A. Jablensky, "Schizophrenia: manifestations,
incidence and course in different cultures," Psychological Medicine 20,
monograph (1992): 1-95.
. 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.
. K. Hopper, "Revisiting the developed versus
developing country distinction in course and outcome in schizophrenia,"
Schizophrenia Bulletin 26 (2000): 835-46.
. J. Wade, "Tardive dyskinesia and cognitive
impairment," Biological Psychiatry 22 (1987): 393-95.
. M. Myslobodsky, "Central determinants of attention
and mood disorder in tardive dyskinesia," Brain and Cognition 23 (1993):
56-70.
. H. Wisniewski, "Neurofibrillary pathology in brains
of elderly schizophrenics treated with neuroleptics," Alzheimer Disease
and Associated Disorders 8 (1994): 211-27.
. M. Chakos, "Increase in caudate nuclei volumes of first-episode
schizophrenic patients 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.
. R. Gur, "Subcortical MRI volumes in neuroleptic-naive
and treated patients with schizophrenia," American Journal of Psychiatry
155 (1998): 1711-17.
. P. Seeman, "Dopamine supersensitivity correlates with
D2 HIGH states, implying many paths to psychosis," Proceedings of the
National Academy of Science 102 (2005): 3513-18.
. B. Ho, "Progressive structural brain abnormalities
and their relationship to clinical outcome," Archives of General
Psychiatry 60 (2003): 585-94.
. N. Andreasen, "Longitudinal changes in neurocognition
during the first decade of schizophrenia illness," International Congress
on Schizophrenia Research (2005): 348.
C. Dreifus, "Using imaging to look at changes in the
brain," New York Times,
September 16, 2008.
T. McGlashan, "Rationale and parameters for
medication-free research in psychosis," Schizophrenia Bulletin 32 (2006):
300-302.
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.
National Institute of Mental Health, "The Numbers
Count," accessed at www.nimh.nih.gov on 3/7/2008.
Chapter 7: The Benzo Trap
S. Garfield, "Valium's 40th Birthday," Observer,
February 2, 2003.
E. Shorter, A History of Psychiatry (New York: John Wiley
& Sons, 1997), 161, 181.
A. Tone, The Age of Anxiety (New York: Basic Books, 2009),
15.
American Psychiatry Association, Diagnostic and Statistical
Manual of Mental Disorders (1952), 31.
C. Silverman, The Epidemiology of Depression (Baltimore:
Johns Hopkins Press, 1968), 139.
L. Hollister, "Drugs for emotional disorders,"
Journal of the American Medical Association 23 4 (1975): 942-47.
F. Ayd Jr., Discoveries in Biological Psychiatry
(Philadelphia: Lippincott, 1970), 127.
D. Greenblatt, "Meprobamate: a study of irrational drug
use," American Journal of Psychiatry 127 (1971): 33-39.
C. Essig, "Addiction to nonbarbiturate sedative and tranquillizing
drugs," Clinical Pharmacology & Therapeutics 5 (1964): 334-43.
"Letdown for Miltown," Time, April 30, 1965.
Tone, The Age of Anxiety, 171.
M. Smith, Small Comfort (New York: Praeger, 1985), 78.
Tone, The Age of Anxiety, 172.
G. Cant, "Valiumania," New York Times, February 1,
1976.
R. Hughes, The Tranquilizing of America (New York: Harcourt
Brace Jovanovich, 1979), 8.
Tone, The Age of Anxiety, 176.
Committee on the Review of Medicines, "Systematic
review of the benzodiazepines," British Medical Journal 280 (1980):
910-12.
Editorial, "Benzodiazepines on trial," British
Medical Journal 288 (1984): 1101-12.
Smith, Small Comfort, 32.
. 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.
. IMS Health, "Top therapeutic classes by U.S.
dispensed prescriptions," 2006 and 2007 reports.
K. Solomon, "Pitfalls and prospects in clinical
research on antianxiety drugs,"
Journal of Clinical Psychiatry 39 (1978): 823-31.
. A. Shapiro, "Diazepam: how much better than
placebo?" Journal of Psychiatric Research 17 (1983): 51-73.
. C. Gudex, "Adverse effects of benzodiazepines,"
Social Science & Medicine 33 (1991): 587-96.
. J. Martin, "Benzodiazepines in generalized anxiety
disorder," Journal of Psychopharmacology 21 (2007): 774-82.
. Malcolm Lader interview, January 12, 2009.
. B. Maletzky, "Addiction to diazepam,"
International Journal of Addictions 11 (1976): 95-115.
. A. Kales, "Rebound insomnia," Science 201
(1978): 1039-40.
. H. Petursson, "Withdrawal from long-term
benzodiazepine treatment," British Medical Journal 283 (1981): 643-35.
. H. Ashton, "Benzodiazepine withdrawal," British
Medical Journal 288 (1984): 1135-40.
. H. Ashton, "Protracted withdrawal syndromes from
benzodiazepines," Journal of Substance Abuse Treatment 9 (1991): 19-28.
P. Cowen, "Abstinence symptoms after withdrawal of
tranquillising drugs," Lancet
2, 8294(1982): 360-62.
. H. Ashton, "Benzodiazepine withdrawal," British
Medical Journal 288 (1984): 1135-40.
. H. Ashton, Benzodiazepines: How They Work and How to
Withdraw (Newcastle upon Tyne: University of Newcastle, 2000), 42.
. H. Ashton, "Protracted withdrawal syndromes from
benzodiazepines," Journal of Substance Abuse Treatment 9 (1991): 19-28.
. K. Rickels, "Long-term benzodiazepine users 3 years
after participation in a discontinuation program," American Journal of
Psychiatry 148 (1991): 757-61.
. K. Rickels, "Psychomotor performance of long-term
benzodiazepine users before, during, and after benzodiazepine
discontinuation," Journal of Clinical Psychopharmacology 19 (1999):
107-13.
. S. Patten, "Self-reported depressive symptoms
following treatment with corticosteroids and sedative-hypnotics,"
International Journal of Psychiatry in Medicine 26 (1995): 15-24.
. Ashton, Benzodiazepines, 8.
. A. Pelissolo, "Anxiety and depressive disorders in
4,425 long term benzodiazepine users in general practice," Encephale 33
(2007): 32-38.
. Hughes, The Tranquilizing of America, 17.
. S. Golombok, "Cognitive impairment in long-term
benzodiazepine users," Psychological Medicine 18 (1988): 365-74.
. M. Barker, "Cognitive effects of long-term
benzodiazepine use," CNS Drugs 18 (2004): 37-48.
. WHO Review Group, "Use and abuse of
benzodiazepines," Bulletin of the World Health Organization 61 (1983):
551-62.
45. Maletzky, "Addiction to diazepam."
. R. Caplan, "Social effects of diazepam use,"
Social Science & Medicine 21 (1985): 887-98.
H. Ashton, "Tranquillisers," British Journal of
Addiction 84 (1989): 541-46.
. Ashton, Benzodiazepines, 12.
. Stevan Gressitt interview, January 9, 2009.
. U.S. Department of Health 6c Human Services, SAMHSA,
Mental Health, United States (2002).
. Government Accountability Office, Young Adults with
Serious Mental Illness, June 2008.
. 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.
. Malcolm Lader interview, January 12, 2009.
Chapter 8: An Episodic Illness Turns Chronic
C. Dewa, "Depression in the workplace," A Report
to the Ontario Roundtable on Appropriate Prescribing, November 2001.
A. Solomon, The Noonday Demon (New York: Simon &
Schuster, 2001), 289.
C. Goshen, editor, Documentary History of Psychiatry (New
York: Philosophical Library, 1967), 118-20.
Solomon, The Noonday Demon, 286.
E. Wolpert, editor, Manic-Depressive Illness (New York:
International Universities Press, 1997), 34.
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.
E Ayd, Recognizing the Depressed Patient (New York: Grune
& Stratton, 1961), 13.
A. Zis, "Major affective disorder as a recurrent
illness," Archives of General Psychiatry 36 (1979): 835-39.
G. Winokur, Manic Depressive Illness (St. Louis: The C.V.
Mosby Company, 1969), 19-20.
T. Rennie, "Prognosis in manic-depressive
psychoses," American Journal of Psychiatry 98 (1941): 801-14. See table on
page 811.
G. Lundquist, "Prognosis and course in manic-depressive
psychoses," Acta Psychi- atrica Scandinavica, suppl. 35 (1945): 7-93.
D. Schuyler, The Depressive Spectrum (New York: Jason
Aronson, 1974), 49.
J. Cole, "Therapeutic efficacy of antidepressant
drugs," Journal of the American Medical Association 190 (1964): 448-55.
N. Kline, "The practical management of
depression," Journal of the American Medical Association 190 (1964):
122-30.
Winokur, Manic Depressive Illness, 19.
Schuyler, The Depressive Spectrum, 47.
Medical Research Council, "Clinical trial of the
treatment of depressive illness,"
British Medical Journal 1 (1965): 881-86.
A. Smith, "Studies on the effectiveness of
antidepressant drugs," Psychopharmacology Bulletin 5 (1969): 1-53.
. 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.
. I. Elkin, "NIMH treatment of depression collaborative
research program," Archives of General Psychiatry 47 (1990): 682-88.
. A. Khan, "Symptom reduction and suicide risk in
patients treated with placebo in antidepressant clinical trials," Archives
of General Psychiatry 57 (2000): 311-17.
. E. Turner, "Selective publication of antidepressant
trials and its influence on apparent efficacy," New England Journal of Medicine
358 (2008): 252-60.
. I. Kirsch, "Initial severity and antidepressant
benefits," PLoS Medicine 5 (2008): 260-68.
. G. Parker, "Antidepressants on trial," British
Journal of Psychiatry 194 (2009): 1-3.
. C. Barbui, "Effectiveness of paroxetine in the treatment
of acute major depression in adults," Canadian Medical Association Journal
178 (2008): 296-305.
. J. Ioannidis, "Effectiveness of
antidepressants," Philosophy, Ethics, and Humanities in Medicine 3 (2008):
14.
. Hypericum Trial Study Group, "Effect of Hypericum
perforatum in major depressive disorder," Journal of the American Medical
Association 287 (2002): 1807-14.
. J.D. Van Scheyen, "Recurrent vital depressions,"
Psychiatria, Neurologia, Neuro- chirurgia76 (1973): 93-112.
. Ibid.
. R. Mindham, "An evaluation of continuation therapy
with tricyclic antidepressants in depressive illness," Psychological
Medicine 3 (1973): 5-17.
. M. Stein, "Maintenance therapy with
amitriptyline," American Journal of Psychiatry 137(1980): 370-71.
R. Prien, "Drug therapy in the prevention of
recurrences in unipolar and bipolar affective disorders," Archives of
General Psychiatry 41 (1984): 1096-1104. See table
6 and figure 2.
. M. Shea, "Course of depressive symptoms over
follow-up," Archives of General Psychiatry 49 (1992): 782-87.
. A. Viguera, "Discontinuing antidepressant treatment
in major depression," Harvard Review of Psychiatry 5 (1998): 293-305.
P. Haddad, "Antidepressant discontinuation
reactions," British Medical Journal 316 (1998): 1105-6.
. G. Fava, "Do antidepressant and antianxiety drugs
increase chronicity in affective disorders?" Psychotherapy and
Psychosomatics 61 (1994): 125-31.
G. Fava, "Can long-term treatment with antidepressant
drugs worsen the course of depression?" Journal of Clinical Psychiatry 64
(2003): 123-33.
. Ibid.
. 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.
. R. Baldessarini, "Risks and implications of
interrupting maintenance psychotropic drug therapy," Psychotherapy and
Psychosomatics 63 (1995): 137-41.
. R. El-Mallakh, "Can long-term antidepressant use be
depressogenic?" Journal of Clinical Psychiatry 60 (1999): 263.
. "Editorial sparks debate on effects of psychoactive
drugs," Psychiatric News, May 20, 1994.
. Consensus Development Panel, "Mood disorders,"
American Journal of Psychiatry
142 (1985): 469-76.
. R. Hales, editor, Textbook of Psychiatry (Washington, DC:
American Psychiatric Press, 1999), 525.
J. Geddes, "Relapse prevention with antidepressant drug
treatment in depressive disorders," Lancet 361 (2003): 653-61.
. L. Judd, "Does incomplete recovery from first lifetime
major depressive episode herald a chronic course of illness?" American
Journal of Psychiatry 157 (2000): 1501-4.
. R. Tranter, "Prevalence and outcome of partial
remission in depression," Journal of Psychiatry and Neuroscience 27
(2002): 241-47.
Hales, Textbook of Psychiatry, 547.
. J. Rush, "One-year clinical outcomes of depressed
public sector outpatients," Biological Psychiatry 56 (2004): 46-53.
. Ibid.
. D. Warden, "The star*d project results," Current
Psychiatry Reports 9 (2007): 449-59.
NIMH, Depression (2007): 3. (NIH Publication 07-3561.)
. D. Deshauer, "Selective serotonin reuptake inhibitors
for unipolar depression,"
Canadian Medical Association Journal 178 (2008): 1293-1301.
. C. Ronalds, "Outcome of anxiety and depressive
disorders in primary care," British Journal of Psychiatry 171 (1997):
427-33.
E. Weel-Baumgarten, "Treatment of depression related to
recurrence," Journal of Clinical Pharmacy and Therapeutics 25 (2000):
61-66.
. S. Patten, "The impact of antidepressant treatment on
population health," Population Health Metrics 2 (2004): 9.
. D. Goldberg, "The effect of detection and treatment
on the outcome of major depression in primary care," British Journal of
General Practice 48 (1998): 1840-44.
Dewa, "Depression in the workplace."
. W. Coryell, "Characteristics and significance of
untreated major depressive disorder," American Journal of Psychiatry 152
(1995): 1124-29.
. J. Moncrieff, "Trends in sickness benefits in Great
Britain and the contribution of mental disorders," Journal of Public
Health Medicine 22 (2000): 59-67.
. T. Helgason, "Antidepressants and public health in
Iceland," British Journal of Psychiatry 184 (2004): 157-62.
. R. Rosenheck, "The growth of psychopharmacology in
the 1990s," International Journal of Law and Psychiatry 28 (2005): 467-83.
. 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.
. Ibid. Also see M. Posternak, "Untreated short-term
course of major depression,"
Journal of Affective Disorders 66 (2001): 139-46.
J. Cole, editor, Psychopharmacology (Washington, DC:
National Academy of Sciences, 1959), 347.
. 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.
. M. Fava, "A cross-sectional study of the prevalence
of cognitive and physical symptoms during long-term antidepressant
treatment," Journal of Clinical Psychiatry 67 (2006): 1754-59.
. 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
D. Healy, Mania (Baltimore: Johns Hopkins University Press,
2008), 16, 41, 43.
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.
C. Silverman, The Epidemiology of Depression (Baltimore:
Johns Hopkins University Press, 1968), 139.
G. Winokur, Manic Depressive Illness (St. Louis: The C.V.
Mosby Company, 1969), 19.
F. Wertham, "A group of benign chronic psychoses,"
American Journal of Psychiatry 9 (1929): 17-78.
G. Lundquist, "Prognosis and course in manic-depressive
psychoses," Acta Psychiatrica Scandinavica, suppl. 35 (1945): 7-93.
M. Tsuang, "Long-term outcome of major psychoses,"
Archives of General Psychiatry 36 (1979): 1295-1301.
Winokur, Manic Depressive Illness, 21.
NIMH, The Numbers Count: Mental Disorders in America,
accessed at www.nimh.nih.gov on 3/7/2008.
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
alcohol use and first manic episode," Pharmacology
Biochemistry and Behavior 86 (2007): 395-400.
S. Strakowski, "The effects of antecedent substance
abuse on the development of first-episode psychotic mania," Journal of
Psychiatric Research 30 (1996): 59-68.
J. Goldberg, "Overdiagnosis of bipolar disorder among substance
use disorder inpatients with mood instability," Journal of Clinical
Psychiatry 69 (2008): 1751-57.
M. Van Laar, "Does cannabis use predict the first
incidence of mood and anxiety disorders in the adult population?"
Addiction 102 (2007): 1251-60.
G. Crane, "The psychiatric side effects of
iproniazid," American Journal of Psychiatry 112 (1956): 494-501.
J. Angst, "Switch from depression to mania," Psych
op athology 18 (1985): 140-54.
American Psychiatric Association, Practice Guidelines for
Major Depressive Disorder in Adults (Washington, DC: APA, 1993), 22.
A. Martin, "Age effects on antidepressant-induced manic
conversion," Archives of Pediatrics & Adolescent Medicine 158 (2004):
773-80.
J. Goldberg, "Risk for bipolar illness in patients
initially hospitalized for unipolar depression," American Journal of
Psychiatry 158 (2001): 1265-70.
R. El-Mallakh, "Use of antidepressants to treat
depression in bipolar disorder," Psychiatric Services 53 (2002): 58-84.
. 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.
. G. Fava, "Can long-term treatment with antidepressant
drugs worsen the course of depression?" Journal of Clinical Psychiatry 64
(2003): 123-33.
L. Judd, "The prevalence and disability of bipolar
spectrum disorders in the US population," Journal of Affective Disorders
73 (2003): 123-31.
. J. Angst, "Toward a re-definition of subthreshold
bipolarity," Journal of Affective Disorders 73 (2003): 133-46.
Ibid; Judd, "The prevalence and disability."
. R. Fieve, Moodswing (New York: William Morrow and Company,
1975), 13.
. For a history of lithium, see Healy, Mania, and J.
Moncrieff, The Myth of the Chemical Cure (New York: Palgrave MacMillan, 2008).
S. Tyrer, "Lithium in the treatment of mania,"
Journal of Affective Disorders 8 (1985): 251-57.
. J. Baker, "Outcomes of lithium discontinuation,"
Lithium 5 (1994): 187-92.
. R. Baldessarini, "Discontinuing lithium maintenance
treatment in bipolar disorders," Bipolar Disorders 1 (1999): 17-24.
G. Faedda, "Outcome after rapid v. gradual
discontinuation of lithium treatment in bipolar disorders," Archives of
General Psychiatry 50 (1993): 448-55.
J. Himmelhoch, "On the failure to recognize lithium failure,"
Psychiatric Annals 24 (1994): 241-50.
J. Moncrieff, The Myth of the Chemical Cure (London: Palgrave
Macmillan, 2008), 199.
. G. Goodwin, "Recurrence of mania after lithium
withdrawal," British Journal of Psychiatry 164 (1994): 149-52.
. 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.
. J. Goldberg, "Lithium treatment of bipolar affective
disorders under naturalistic fol- lowup conditions," Psychopharmacology
Bulletin 32 (1996): 47-54.
. M. Gitlin, "Relapse and impairment in bipolar
disorder," American Journal of Psy-
.chiatry 152 (1995): 1635-40.
J. Moncrieff, "Lithium: evidence reconsidered,"
British Journal of Psychiatry 171 (1997): 113-19.
. F. Goodwin, Manic-Depressive Illness (New York: Oxford
University Press, 1990), 647.
. A. Zis, "Major affective disorder as a recurrent
illness," Archives of General Psychiatry 36 (1979): 835-39.
. A. Koukopoulos, "Rapid cyclers, temperament, and
antidepressants," Comprehensive Psychiatry 24 (1983): 249-58.
. N. Ghaemi, "Diagnosing bipolar disorder and the
effect of antidepressants," Journal of Clinical Psychiatry 61 (2000):
804-809.
. N. Ghaemi, "Antidepressants in bipolar
disorder," Bipolar Disorders 5 (2003): 421-33.
. R. El-Mallakh, "Use of antidepressants to treat
depression in bipolar disorder," Psychiatric Services 53 (2002): 580-84.
. 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.
. N. Ghaemi, "Treatment of rapid-cycling bipolar disorder,"
American Journal of Psychiatry 165 (2008): 300-301.
. C. Schneck, "The prospective course of rapid-cycling
bipolar disorder," American Journal of Psychiatry 165 (2008): 370-77.
. L. Judd, "The long-term natural history of the weekly
symptomatic status of bipolar I disorder," Archives of General Psychiatry
59 (2002): 530-37.
. 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.
. 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.
. 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.
. L. Judd, "Residual symptom recovery from major
affective episodes in bipolar disorders and rapid episode
relapse/recurrence," Archives of General Psychiatry 65 (2008): 386-94.
. C. Zarate, "Functional impairment and cognition in
bipolar disorder," Psychiatric Quarterly 71 (2000): 309-29.
Gitlin, "Relapse and impairment."
R Keck, "12-month outcome of patients with bipolar
disorder following hospitalization for a manic or a mixed episode,"
American journal of Psychiatry 155 (1998): 646-52.
D. Kupfer, "Demographic and clinical characteristics of
individuals in a bipolar disorder case registry," journal of Clinical
Psychiatry 63 (2002): 120-25.
N. Huxley, "Disability and its treatment in bipolar
disorder patients," Bipolar Disorders 9 (2007): 183-96.
T. Goldberg, "Contrasts between patients with affective
disorders and patients with schizophrenia on a neuropsychological test
battery," American journal of Psychiatry 150 (1993): 1355-62.
J. Zihl, "Cognitive deficits in schizophrenia and
affective disorders," Acta Psychi- atrica Scandinavica 97 (1998): 351-57.
. F. Dickerson, "Outpatients with schizophrenia and
bipolar I disorder," Psychiatry Research 102 (2001): 21-27.
. G. Malhi, "Neuropsychological deficits and functional
impairment in bipolar depression, hypomania and euthymia," Bipolar
Disorders 9 (2007): 114-25.
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.
. M. Pope, "Determinants of social functioning in
bipolar disorder," Bipolar Disorders 9 (2007): 38-44.
C. Zarate, "Antipsychotic drug side effect issues in
bipolar manic patients," Journal of Clinical Psychiatry 61, suppl. 8
(2000): 52-61.
. C. Zarate, "Functional impairment and cognition in
bipolar disorder," Psychiatric Quarterly 71 (2000): 309-29.
. D. Kupfer, "The increasing medical burden in bipolar
disorder," journal of the American Medical Association 293 (2005):
2528-30.
L. Citrome, "Toward convergence in the medication
treatment of bipolar disorder and schizophrenia," Harvard Review of
Psychiatry 13 (2005): 28-42.
. Huxley, "Disability and its treatment."
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.
W. Eaton, "The burden of mental disorders,"
Epidemiology Review 30 (2008): 1-14.
Chapter 10: An Epidemic Explained
Interview with Amy Upham, June 14, 2009.
M. Morgan, "Prospective analysis of premature mortality
in schizophrenia in relation to health service engagement," Psychiatry
Research 117 (2003): 127-35 ;
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).
S. Saha, "A systematic review of mortality in
schizophrenia," Archives of General Psychiatry 64 (2007): 1123-31 ; L.
Appleby, "Sudden unexplained death in psychiatric 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
B. Carey, "What's wrong with a child? Psychiatrists
often disagree," New York Times, November 11, 2006.
R. Kessler, "Mood disorders in children and
adolescents," Biological Psychiatry 49 (2001): 1002-14.
J. O'Neal, Child and Adolescent Psychopharmacology Made
Simple (Oakland, CA: New Harbinger Publications, 2006), 6.
R. Mayes, Medicating Children (Cambridge, MA: Harvard
University Press, 2009), 46.
G. Jackson, "Postmodern psychiatry," unpublished
paper, September 2, 2002.
Mayes, Medicating Children, 54.
Ibid, 61.
R. Mayes, "ADHD and the rise in stimulant use among
children," Harvard Review of Psychiatry 16 (2008): 151-66.
G. Golden, "Role of attention deficit hyperactivity
disorder in learning disabilities,"
Seminars in Neurology 11 (1991): 35-41.
NIH Consensus Development Conference statement,
"Diagnosis and treatment of attention deficit hyperactivity
disorder," November 16-18, 1998.
P. Breggin, Talking Back to Ritalin (Cambridge, MA: Perseus
Publishing, 2001), 180.
S. Hyman, "Initiation and adaptation: a paradigm for
understanding psychotropic drug action," American Journal of Psychiatry
153 (1996): 151-61.
Breggin, Talking Back to Ritalin, 83.
H. Rie, "Effects of methylphenidate on underachieving
children," Journal of Consulting and Clinical Psychology 44 (1976):
250-60.
C. Cunningham, "The effects of methylphenidate on the
mother-child interactions of hyperactive identical twins," Developmental
Medicine & Child Neurology 20 (1978): 634-42.
N. Fiedler, "The effects of stimulant drugs on
curiosity behaviors of hyperactive boys," Journal of Abnormal Child
Psychology 11 (1983): 193-206.
T. Davy, "Stimulant medication and short attention span,"
Journal of Developmental & Behavioral Pediatrics 10 (1989): 313-18.
D. Granger, "Perceptions of methylphenidate effects on
hyperactive children's peer interactions," Journal of Abnormal Child
Psychology 21 (1993): 535-49.
J. Swanson, "Effects of stimulant medication on
learning in children with ADHD,"
Journal of Learning Disabilities 24 (1991): 219-30.
. Breggin, Talking Back to Ritalin, 92.
. J. Richters, "NIMH Collaborative Multisite Multimodal
Treatment Study of Children with ADHD," Journal of the American Academy of
Child & Adolescent Psychiatry 34 (1995): 987-1000.
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.
. E. Sleator, "How do hyperactive children feel about
taking stimulants and will they tell the doctor?" Clinical Pediatrics 21
(1982): 474-79.
. 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.
. A. Sroufe, "Treating problem children with stimulant
drugs," New England Journal of Medicine 289 (1973): 407-13.
. Ibid.
Rie, "Effects of methylphenidate."
. R. Barkley, "Do stimulant drugs improve the academic
performance of hyperkinetic children?" Clinical Pediatrics 8 (1978):
137-46.
. Swanson, "Effects of stimulant medication."
C. Whalen, "Stimulant pharmacotherapy for attention-deficit
hyperactivity disorders," in S. Fishberg and R. Greenberg, eds., From
Placebo to Panacea (New York: John Wiley & Sons, 1997), 329.
. R. Schachar, "Attention-deficit hyperactivity
disorder," Canadian Journal of Psychiatry 47 (2002): 337-48.
Whalen, "Stimulant pharmacotherapy," 327.
. P. Breggin, "Psychostimulants in the treatment of
children diagnosed with ADHD,"
International Journal of Risk & Safety in Medicine 12
(1993): 3-35.
Ibid.
. Richters, "NIMH Collaborative Multisite."
. 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.
The MTA Cooperative Group, "A 14-month randomized
clinical trial of treatment strategies for attention-deficit/hyperactivity
disorder," Archives of General Psychiatry 56 (1999): 1073-86.
Jensen, "3-year follow-up."
. 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.
. B. Molina, "MTA at 8 years," Journal of the
American Academy of Child & Adolescent Psychiatry 48 (2009): 484-500.
. C. Miranda, "ADHD drugs could stunt growth,"
Daily Telegraph (UK), November 12, 2007.
. Breggin, Talking Back to Ritalin; K. Bolla, "The
neuropsychiatry of chronic cocaine abuse," Journal of Neuropsychiatry and
Clinical Neurosciences 10 (1998): 280-89.
. S. Castner, "Long-lasting psychotomimetic
consequences of repeated low-dose amphetamine exposure in rhesus monkeys,"
Neuropsychopharmacology 20 (1999): 10-28.
. W. Carlezon, "Enduring behavioral effects of early
exposure to methylphenidate in rats," Biological Psychiatry 54 (2003):
1330-37.
. C. Bolanos, "Methylphenidate treatment during pre-
and periadolescence alters behavioral responses to emotional stimuli at
adulthood," Biological Psychiatry 54 (2003): 1317-29.
. J. Zito, "Rising prevalence of antidepressants among
US youths," Pediatrics 109 (2002): 721-27.
. R. Fisher, Prom Placebo to Panacea (New York: John Wiley
& Sons, 1997), 309.
. 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.
. Editorial, "Depressing research," Lancet 363
(2004): 1335.
. T. Laughren, Memorandum, "Background comments for
Feb. 2, 2004 meeting of psychopharmacological drugs advisory committee,"
January 5, 2004. Accessed at fda.gov.
. J. Leo, "The SSRI trials in children," Ethical
Human Psychology and Psychiatry 8 (2006): 29-41.
. C. Whittington, "Selective serotonin reuptake
inhibitors in childhood depression,"
Lancet 363 (2004): 1341-45.
. Editorial, "Depressing research," Lancet 363
(2004): 1335.
. J. Jureidini, "Efficacy and safety of antidepressants
for children and adolescents,"
British Medical Journal (2004): 879-83.
. T. Wilens, "A systematic chart review of the nature
of psychiatric adverse events in children and adolescents treated with
selective serotonin reuptake inhibitors," Journal of Child and Adolescent
Psychopharmacology 13 (2003): 143-52.
. T. Gualtieri, "Antidepressant side effects in
children and adolescents," Journal of Child and Adolescent
Psychopharmacology 16 (2006): 147-57.
P. Breggin, Brain-Disabling Treatments in Psychiatry (New
York: Springer Publishing Company, 2008), 153.
. D. Papolos, The Bipolar Child (New York: Broadway Books,
2000), xiv.
. C. Moreno, "National trends in the outpatient
diagnosis and treatment of bipolar disorder in youth," Archives of General
Psychiatry 64 (2007): 1032-39.
. J. Kluger, "Young and Bipolar," Time, August 19,
2002.
. L. Lurie, "Psychoses in children," Journal of
Pediatrics 36 (1950): 801-9.
. Ibid.
. B. Hall, "Our present knowledge about
manic-depressive states in childhood," Nervous Child 9 (1952): 319-25.
J. Anthony, "Manic-depressive psychosis in
childhood," Journal of Child Psychology and Psychiatry 1 (1960): 53-72.
. W. Weinberg, "Mania in childhood," American
Journal of Diseases of Childhood
130(1976): 380-85.
R. DeLong, "Lithium carbonate treatment of select
behavior disorders in children suggesting manic-depressive illness,"
Journal of Pediatrics 93 (1978): 689-94.
M. Strober, "Bipolar illness in adolescents with major
depression," Archives of General Psychiatry 39 (1982): 549-55.
. R Lewinsohn, "Bipolar disorders in a community sample
of older adolescents," Journal of the American Academy of Child &
Adolescent Psychiatry 34 (1995): 454-63.
G. Carlson, "Manic symptoms in psychiatrically
hospitalized children—what do they mean?" Journal of Affective Disorders
51 (1998): 123-35.
J. Kluger, "Young and Bipolar."
. D. Janowsky, "Proceedings: effect of intravenous
d-amphetamine, 1-amphetamine and methylphenidate in schizophrenics,"
Psychopharmacology Bulletin 19 (1974): 15-24.
E. Cherland, "Psychotic side effects of
psychostimulants," Canadian Journal of Psychiatry 44 (1999): 811-13.
. K. Gelperin, "Psychiatric adverse events associated
with drug treatment of ADHD," FDA, Center for Drug Evaluation and
Research, March 3, 2006.
D. Papolos, "Bipolar disorder, co-occuring conditions,
and the need for extreme caution before initiating drug treatment,"
Bipolar Child Newsletter 1 (November 1999).
. M. DelBello, "Prior stimulant treatment in
adolescents with bipolar disorder," Bipolar Disorders 3 (2001): 53-57.
J. Biederman, "Attention-deficit hyperactivity disorder
and juvenile mania," Journal of the American Academy of Child & Adolescent
Psychiatry 35 (1996): 997-1008.
J. Jain, "Fluoxetine in children and adolescents with
mood disorders," Journal of Child & Adolescent Psychopharmacology 2
(1992): 259-65.
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.
P. Breggin, The Anti-Depressant Fact Book (Cambridge, MA:
Perseus Publishing, 2001), 116.
A. Martin, "Age effects on antidepressant-induced manic
conversion," Archives of Pediatrics & Adolescent Medicine 158 (2004):
773-80.
G. Faedda, "Pediatric onset bipolar disorder,"
Harvard Review of Psychiatry 3 (1995): 171-95.
B. Geller, "Bipolar disorder at prospective follow-up
of adults who had prepubertal major depressive disorder," American Journal
of Psychiatry 158 (2001): 125-27.
D. Cicero, "Antidepressant exposure in bipolar
children," Psychiatry 66 (2003): 317-22.
D. Papolos. "Antidepressant-induced adverse effects in
juvenile-onset bipolar
disorder," paper presented at the Fifth International
Conference on Bipolar Disorder, June 12-14, 2003, Pittsburgh, PA.
. G. Faedda, "Pediatric bipolar disorder," Bipolar
Disorders 6 (2004): 305-13.
. M. Hellander, "Children with bipolar disorder,"
Journal of the American Academy of Child & Adolescent Psychiatry 38 (1999):
495.
H. Marano, "Crisis on the campus," Psychology
Today, May 2, 2002.
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.
. B. Geller, "Child and adolescent bipolar
disorder," Journal of the American Academy of Child & Adolescent
Psychiatry 36 (1997): 1168-76.
. Papolos, "Antidepressant-induced adverse
effects."
. G. Faedda, "Treatment-emergent mania in pediatric
bipolar disorder," Journal of Affective Disorders (82): 149-58.
. R. Pedis, "Long-term implications of early onset in
bipolar disorder," Biological Psychiatry 55 (2004): 875-81.
. B. Birmaher, "Course and outcome of bipolar spectrum
disorder in children and adolescents," Development and Psychopathology 18
(2006): 1023-35.
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.
. T. Goldstein, "Psychosocial functioning among bipolar
youth," Journal of Affective Disorders 114 (2009): 174-83.
. 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.
"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.
. Social Security Administration, annual statistical reports
on the SSI program, 1996 - 2008 ; Social Security Bulletin, Annual Statistical
Supplement, 1988-1992.
. Pediatric Academic Societies, "Pediatric psychiatry
admissions on the rise," May 16, 2000, press release.
D. Satcher, Report of Surgeon General's Conference on
Children's Mental Health
(U.S. Dept. of Health and Human Services, 2001).
. B. Whitford, "Depression, eating disorders and other
mental illnesses are on the rise," Newsweek, August 27, 2008.
U.S. Government Accountability Office, "Young adults
with serious mental illness" (June 2008).
Chapter 12: Suffer the Children
J. Zito, "Psychotropic medication patterns among youth
in foster care," Pediatrics
121 (2008): 157-63.
Chapter 13: The Rise of an Ideology
C. Ross, Pseudoscience in Psychiatry (New York: John Wiley
& Sons, 1995).
G. Klerman, "A debate on DSM-III," American journal
of Psychiatry 141 (1984): 539-42.
M. Sabshin, "Report of the medical director,"
American journal of Psychiatry 137 (1980): 1308.
See blurbs for second edition of The Myth of Mental Illness,
published by Harper &c
Row in 1974.
B. Nelson, "Psychiatry's anxious years," New York
Times, November 2, 1982.
D. Adler, "The medical model and psychiatry's
tasks," Hospital and Community Psychiatry 32 (1981): 387-92.
Sabshin, "Report of the medical director."
Nelson, "Psychiatry's anxious years."
Copy from a Smith Kline and French advertisement that ran
monthly in Mental Hospitals in 1962.
L. Thorne, "Inside Russia's psychiatric jails,"
New York Times Magazine, June 12, 1977.
U.S. Senate, Committee on the Judiciary, Subcommittee to
Investigate Juvenile Delinquency, Drugs in Institutions, 94th Cong., 1st sess.,
1975.
A. Tone, The Age of Anxiety (New York: Basic Books, 2009),
176.
M. Smith, Small Comfort (New York: Praeger, 1985), 32.
Interview with Arthur Piatt, June 8, 2009.
M. Sabshin, "On remedicalization and holism in
psychiatry," Psychosomatics 18 (1977): 7-8.
A. Ludwig, "The medical basis of psychiatry,"
American journal of Psychiatry 134 (1977): 1087-92.
P. Blaney, "Implications of the medical model and its
alternatives," American Journal of Psychiatry 132 (1975): 911-14.
S. Guze, "Nature of psychiatric illness,"
Comprehensive Psychiatry 19 (1978): 295-307.
Adler, "The medical model."
. M. Wilson, "DSM-III and the transformation of
American psychiatry," American journal of Psychiatry 150 (1993): 399-410.
. S. Kirk, The Selling of DSM (New York: Aldine de Gruyter,
1992), 114.
22. Ibid, 134.
. M. Sabshin, "Turning points in twentieth-century
American psychiatry," American Journal of Psychiatry (1990): 1267-74.
Klerman, "A debate on DSM-III."
. J. Maxmen, The New Psychiatrists (New York: New American
Library, 1985), 35,31.
. H. Kutchins, Making Us Crazy (New York: The Free Press,
1997), 248.
Kirk, The Selling of DSM, 115.
. M. Sabshin, "Report of the medical director"
(1980), 1308.
. L. Havens, "Twentieth-century psychiatry,"
American journal of Psychiatry 138 (1981): 1279-87.
. B. Bursten, "Rallying 'round the medical model,"
Hospital and Community Psychiatry 32(1981): 371.
. Sources for this political battle include reviews by
NIMH's "Clinical Programs Projects 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.
. Interview with Loren Mosher, December 1, 2000.
. M. Sabshin, "Report of the medical director,"
American Journal of Psychiatry 138 (1981): 1418-21.
. P. Breggin, Toxic Psychiatry (New York: St. Martin's
Press, 1991), 360.
. Sabshin, "Report of the medical director"
(1981).
. M. Sabshin, "Report of the medical director,"
American Journal of Psychiatry 140 (1983): 1398-1403.
. R. Peele, "Report of the speaker-elect,"
American Journal of Psychiatry 143 (1986): 1348-50.
. M. Sabshin, "Report of the medical director,"
American Journal of Psychiatry 143 (1986): 1342-46.
. M. Sabshin, "Report of the medical director,"
American Journal of Psychiatry 145 (1988): 1338^12.
. Sabshin, "Report of the medical director"
(1981).
41. M. Sabshin, Changing American Psychiatry (Washington,
DC: American Psychiatric Publishing, Inc., 2008), 78.
. Sabshin, "Report of the medical director"
(1983).
. Sabshin, "Report of the medical director"
(1986).
. New York Times, November 26, 1981 ; September 7, 1982 ;
July 29, 1984.
. J. Franklin, "The Mind-Fixers," Baltimore
Evening Sun, July 1984.
. M. Gold, The Good News About Depression (New York: Villard
Books, 1987), xi-xiii.
. N. Andreasen, The Broken Brain (New York: Harper &
Row, 1984), 29-30.
48. Ibid, 138.
49. Franklin, "The Mind-Fixers."
. Sabshin, Changing American Psychiatry, 194.
. M. Dumont, "In bed together at the market,"
American Journal of Orthopsychiatry
60 (1990): 484-85.
. F. Gottlieb, "Report of the speaker," American
Journal of Psychiatry 142 (1985): 1246-49.
. Breggin, Toxic Psychiatry, 46, 357.
. P. Breggin, Medication Madness (New York: St. Martin's Press,
2008), 150.
. S. Boseley, "Scandal of scientists who take money for
papers ghostwritten by drug companies," Guardian, February 7, 2002.
. M. Angel, "Is academic medicine for sale?" New
England Journal of Medicine 342 (2000): 1516-18.
D. Regier, "The NIMH depression awareness, recognition,
and treatment program," American Journal of Psychiatry 145 (1988):
1351-57.
Breggin, Toxic Psychiatry, 14.
E. Foulks, "Advocating for persons who are mentally
ill," Administration and Policy in Mental Health and Mental Health
Services Research 27 (2000): 353-67.
. A. Hatfield, "The National Alliance for the Mentally
111," Community Mental Health Journal 27 (1991): 95-103.
. E. Benedek, "Report of the secretary," American
Journal of Psychiatry 144 (1987): 1381-88.
Breggin, Toxic Psychiatry, 363.
. Foulks, "Advocating for persons."
K. Silverstein, "Prozac.org," Mother Jones,
November/December 1999.
. R. Behar, "The thriving cult of greed and
power," Time, May 6, 1991.
Chapter 14: The Story That Was... and Wasn't Told
D. Healy, Mania (Baltimore: Johns Hopkins University Press,
2008), 132.
G. Carson, The Roguish World of Doctor Brinkley (New York:
Rinehart & Co., 1960).
P. Breggin, Brain-Disabling Treatments in Psychiatry (New
York: Springer Publishing Co., 2008), 390.
"Fluoxetine project team meeting," July 31, 1978,
accessed at healyprozac.com.
"Fluoxetine project team meeting," July 23, 1979,
accessed at healyprozac.com.
J. Cornwell, The Power to Harm (New York: Viking, 1996),
147-48.
D. Healy, Let Them Eat Prozac (New York: New York University
Press, 2004), 39. 8. Ibid, 128.
9. Ibid, 249.
BGA letter to Eli Lilly, May 25, 1984, Forsyth v. Eli Lilly
trial documents, exhibit
42. See baumhedlundlaw.com/media/timeline.
Forsyth v. Eli Lilly trial documents, exhibit 58.
Cornwell, The Power to Harm, 198.
Healy, Let Them Eat Prozac, 35.
P. Breggin, Talking Back to Prozac (New York: St. Martin's
Press, 1994), 41.
Ibid, 46.
Ibid, 90. Also see P. Breggin, Brain-Disabling Treatments in
Psychiatry, 79, 86,91.
D. Graham, "Sponsor's ADR submission on fluoxetine
dated July 17, 1990," FDA document, September 1990.
T. Moore, "Hard to Swallow," Washingtonian,
December 1997.
D. Kessler, "Introducing MEDWatch," Journal of the
American Medical Association
269(1993): 2765-68.
. J. Bremner, "Fluoxetine in depressed patients,"
Journal of Clinical Psychiatry 45 (1984): 414-19.
. J. Feigner, "A comparative trial of fluoxetine and
amitriptyline in patients with major depressive disorder," Journal of
Clinical Psychiatry 46 (1985): 369-72.
. J. Cohn, "A comparison of fluoxetine, imipramine, and
placebo in patients with major depressive disorder," Journal of Clinical
Psychiatry 46 (1985): 26-31.
. J. Wernicke, "The side effect profile and safety of
fluoxetine," Journal of Clinical Psychiatry 46 (1985): 59-67.
. P. Stark, "A review of multicenter controlled studies
of fluoxetine vs. imipramine and placebo in outpatients with major depressive
disorder," Journal of Clinical Psychiatry 46 (1985): 53-58.
25. S. Levine, "A comparative trial of a new antidepressant,
fluoxetine," British Journal of Psychiatry 150 (1987): 653-55.
R. Pary, "Fluoxetine: prescribing guidelines for the
newest antidepressant," Southern Medical Journal 82 (1989): 1005-9.
. D. Regier, "The NIMH depression awareness,
recognition and treatment program,"
American Journal of Psychiatry 145 (1988): 1351-57.
. Healy, Let Them Eat Prozac, 9.
. F. Schumer, "Bye-Bye, Blues," New York, December
18, 1989.
. G. Cowley, "Prozac: A Breakthrough Drug for
Depression," Newsweek, March 26, 1990.
. N. Angier, "New antidepressant is acclaimed but not
perfect," New York Times,
March 29, 1990.
. B. Duncan, "Exposing the mythmakers,"
Psychotherapy Networker, March/April 2000.
. M. Waldholz, "Prozac said to spur idea of
suicide," Wall Street Journal, July 18, 1990.
. 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.
. Memo from Leigh Thompson to Allan Weinstein, February 7,
1990, accessed at healyprozac.com
. Memo from Mitch Daniels to Leigh Thompson, "Upcoming
TV appearance," April 15, 1991, accessed at healyprozac.com.
Ibid.
. T. Burton, "Medical flap: Anti-depression drug of Eli
Lilly loses sales after attack by sect," Wall Street Journal, April 19,
1991.
. L. Garnett, "Prozac revisited," Boston Globe,
May 7, 2000.
. R. Behar, "The Thriving Cult of Greed and
Power," Time, May 6, 1991.
. T. Burton, "Panel finds no credible evidence to tie
Prozac to suicides and violent behavior," Wall Street Journal, September
23, 1991.
. S. Begley, "Beyond Prozac," Newsweek, February
7, 1994.
. 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.
. "High Anxiety," Consumer Reports, January 1993.
. C. Ballenger, "Alprazolam in panic disorder and
agoraphobia," Archives of General Psychiatry 45 (1988): 413-22.
. R. Noyes, "Alprazolam in panic disorder and
agoraphobia," Archives of General Psychiatry 45 (1988): 423-28.
J. Pecknold, "Alprazolam in panic disorder and
agoraphobia," Archives of General Psychiatry 45 (1988): 429-36.
. Ballenger, "Alprazolam in panic disorder."
. Noyes, "Alprazolam in panic disorder."
. Pecknold, "Alprazolam in panic disorder."
. I. Marks, "The 'efficacy' of alprazolam in panic
disorder and agoraphobia,"
Archives of General Psychiatry 46 (1989): 668-72.
I. Marks, "Reply to comment on the London/Toronto
study," British Journal of Psychiatry 162 (1993): 790-94.
. Breggin, Toxic Psychiatry, 344-53.
F. Pollner, "Don't overlook panic disorder,"
Medical World News, October 1, 1991.
. J. Randal, "In a panic?" St. Louis
Post-Dispatch, October 7, 1990.
. H. Brown, "Panic attacks keeps thousands from malls,
off roads," Associated Press, November 19, 1990.
R. Davis, "When panic is disabling," Chicago
Sun-Times, June 29, 1992.
. "High Anxiety," Consumer Reports.
. 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.
. Approval letter from Robert Temple to Janssen Research
Foundation, December 29, 1993.
. S. Marder, "The effects of risperidone on the five
dimensions of schizophrenia derived by factor analysis," Journal of
Clinical Psychiatry 58 (1997): 538-46.
"New hope for schizophrenia," Washington Post,
February 16, 1993.
. "Seeking safer treatments for schizophrenia,"
New York Times, January 15, 1992.
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.
. C. Beasley, "Efficacy of olanzapine," Journal of
Clinical Psychiatry 58, suppl. 10 (1997): 7-12.
"Psychosis drug from Eli Lilly racks up gains,"
Wall Street Journal, April 14, 1998.
"A new drug for schizophrenia wins approval from the
FDA," New York Times,
October 2, 1996.
. "Schizophrenia, close-up of the troubled brain,"
Parade, November 21, 1999.
. "Mental illness aid," Chicago Tribune, June 4,
1999.
"Lives recovered," Los Angeles Times, January 30,
1996.
. P. Weiden, Breakthroughs in Antipsychotic Medications (New
York: WW Norton, 1999), 26
Wall Street Journal, "Psychosis drug from Eli
Lilly."
. "High Anxiety," Consumer Reports.
. J. Lieberman, "Effectiveness of antipsychotic drugs
in patients with schizophrenia,"
New England Journal of Medicine (2005): 1209-33.
. L. Davies, "Cost-effectiveness of first- v.
second-generation antipsychotic drugs."
British Journal of Psychiatry 191 (2007): 14-22.
. P. Tyrer, "The spurious advance of antipsychotic drug
therapy," Lancet 373 (2009): 4-5.
Interview with Peter Breggin, October 10, 2008.
. Healy interview on CBS News and Current Affairs, June 12,
2001.
. D. Healy, "Psychopharmacology and the government of
the self," talk given November 30, 2000, at the University of Toronto.
. E-mail from David Goldbloom to David Healy, December 7,
2000.
. Interview with Healy by e-mail, July 4, 2009.
Memo from Larry Carpman to Steve Kurkjian, April 11, 2000.
"Science News from 2007, " NIMH website, accessed
on July 2, 2009.
NIMH press release, July 20, 2007.
. J. Sharkey, "Delusions; paranoia is universal,"
New York Times, August 2, 1998.
Search of NAMI website on July 7, 2009.
R. Hales, The American Psychiatric Publishing Textbook of
Psychiatry (Arlington, VA: American Psychiatric Publishing, 2008).
Chapter 15: Tallying Up the Profits
D. Carlat, "Dr. Drug Rep," New York Times,
November 25, 2007. 2. NAMI IRS 990 Form, 2000.
B. Koerner, "First you market the disesase, then you
push the pills to treat it,"
Guardian, July 30, 2002.
E. Tanouye, "Antidepressant makers study kids' market,"
Wall Street Journal, April 4, 1997.
B. Strauch, "Use of antidepression medicine for young
patients has soared," New York Times, August 10, 1997.
Tanouye, "Antidepressant makers."
Deposition of Joseph Biederman in legal case of Avila v.
Johnson & Johnson Co.,
February 26, 2009, pages 139, 231, 232, 237.
J. Biederman, "Attention-deficit hyperactivity disorder
and juvenile mania," Journal of the American Academy of Child &
Adolescent Psychiatry 35 (1996): 997-1008.
Deposition of Joseph Biederman, p. 158.
Margaret Williams, report on a sales call, May 17, 2002.
J. J. Zorc, "Expenditures for psychotropic medications
in the United States in 1985," American Journal of Psychiatry 148 (1991):
644-4 7
"Top therapeutic classes by U.S. sales, 2008, "
IMS Health.
S. Giled, "Better but not best," Health Affairs 28
(2009): 637-48.
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.
J. Pereira, "Emory professor steps down," Wall
Street Journal, December 23, 2008.
C. Schneider, "Emory psychiatrist reprimanded over
outside work," Atlanta Journal-Constitution, June 11, 2009.
G. Harris, "Radio host has drug company ties," New
York Times, November 22, 2008.
GlaxoSmithKline internal memo, "Seroxat/Paxil
adolescent depression. Position piece on the phase III studies," October
1998.
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.
. E. Ramshaw, "Senator questions doctors' ties to drug
companies," Dallas Morning News, September 24, 2008.
. L. Kowalczyk, "US cites Boston psychiatrist in case
vs. drug firm," Boston Globe,
March 6, 2009.
. G. Harris, "Lawmaker calls for registry of drug firms
paying doctors," New York Times, August 4, 2007.
. G. Harris, "Researchers fail to reveal full drug
pay," New York Times, June 8, 2008.
. Avila v. Johnson & Johnson, deposition of Joseph
Biederman, February 26, 2009, 119.
. J. Biederman, Annual Report 2002: The Johnson & Johnson
Center for Pediatric Psychopathology at the Massachusetts General Hospital.
. J. Olson, "Drug makers step up giving to Minnesota
psychiatrists," Pioneer Press,
August 27, 2007.
Margaret Williams, reports on sales calls, April 20, 2001,
and April 8, 2002.
. Eli Lilly grant registry, 2009, 1st quarter.
. E. Mundell, "U.S. spending on mental health care
soaring," HealthDay, August 6, 2009.
. 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
MindFreedom, "Original statement by the fast for
freedom in mental health," July 28, 2003.
Letter from James Scully to David Oaks, August 12, 2003.
Letter from MindFreedom scientific panel to James Scully,
August 22, 2003.
APA statement on "diagnosis and treatment of mental
disorders," September 26, 2003.
Letter from MindFreedom scientific panel to James Scully,
December 15, 2003.
Interview with David Oaks, October 4, 2009.
J. Modrow, How to Become a Schizophrenic (Seattle: Apollyon
Press, 1992), ix.
Interview with David Healy in Bangor, Wales, September 4,
2009.
D. Healy, "Psychiatric bed utilization," Psychological
Medicine 31 (2001): 779-90 ;
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 psychosis, 1875-1924, and 1994-2003.
Interviews with Yrjo Alanen, Jukka Aaltonen, and Viljo Rakkolainen
in Turku, Finland, September 7, 2009.
V. Lehtinen, "Two-year outcome in first-episode
psychosis treated according to an integrated model," European Psychiatry
15 (2000): 312-20.
Interview with Jaakko Seikkula in Jyvaskyla, Finland,
September 9, 2009.
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 psychosis," Society of Clinical Psychology 10
(2000): 20-29 ; J. Seikkula, "Open dialogue, good and poor outcome,"
Journal of Constructivist Psychology 14 (2002): 267-86 ; J. Seikkula,
"Open dialogue approach: treatment principles and preliminary results of a
two-year follow-up on first episode schizophrenia," Ethical Human Sciences
Services 5 (2003): 163-82.
Interviews with staff at Keropudas Hospital in Tornio,
Finland, September 10 and 11,2009.
Outcomes for 2002-200 6 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.
J. Cullberg, "Integrating intensive psychosocial
therapy and low dose medical treatment in a total material of first episode
psychotic patients compared to treatment as usual," Medical Archives 53
(1999): 167-70.
W. Buchan, Domestic Medicine (Boston: Otis, Broaders, and
Co., 1846), 307.
National Institute for Health and Clinical Excellence,
"Depression," December 2004.
Interview with Andrew McCulloch in London, September 3,
2009.
. F. Dimeo, "Benefits from aerobic exercise in patients
with major depression," British Journal of Sports Medicine 35 (2001):
114-17 ; K. Knubben, "A randomized, controlled study on the effects of a
short-term endurance training programme in patients 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.
. J. Blumenthal, "Effects of exercise training on older
patients with major depression," Archives of Internal Medicine 159 (1999):
2349-56.
. Ibid.
. Interviews with Tony Stanton and staff at Seneca Center in
San Leandro, California, July 13 and 14, 2009.
. Interviews with Keith Scott and Chris Gordon, Framingham,
Massachusetts, October 1, 2009.
. Ibid.
. Interview with Jim Gottstein in Anchorage, Alaska, May 10,
2009.
M. Ford, "The psychiatrist's double bind,"
American Journal of Psychiatry 137 (1980): 332-39.
. Myers v. Alaska Psychiatric Institute, Alaska Supreme
Court No. S-11021.
. Interview with Susan Musante in Anchorage, Alaska, May 10,
2009.
Epilogue
1. E. Whipple, Character and Characteristic Men (Boston:
Ticknor & Fields, 1866), 1.
A C K N O W L E D G M E N T S
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 A C K N O
W L E D G M E N T S
Jason Smith, and Kelley Smith welcomed me into their homes.
In California, Tony Stanton organized two days of interviews with
administrators, staff, and children at the Seneca Center. Throughout this
project, David Healy answered my inquiries, and when I interviewed 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 Alanen, 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 narrative arc, and when it came time to edit the
manuscript, he improved it in innumerable ways. Every writer should be so lucky
to have an agent as supportive as Theresa Park and an editor as talented 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.
I N D E X
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., 355-5 7 Ambien (Zolpidem), 23
American Foundation for Suicide Prevention, 327
American Medical Association, 39 ; drug company alliances,
54-5 7
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, 273-7 4
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, 289-9 1 ; 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,
211-12 ; tricyclics, 153-55, 157, 158,
186, 198, 199, 229, 234, 240, 249,
285, 288 withdrawal psychosis, 250.
See also SSRIs; specific brand names antipsychotics. See
neuroleptics Antipsychotics and Mood Stabilizers
(Stahl), 192
anxiety, 28, 51-53, 126-47 ; case studies,
139-45 ; disability and, 5, 140, 146-47,
209 ; drug-based treatment, 129-39 ; hiding the evidence,
307-12 ; iatrogenic effects of drugs, 209 ; social anxiety disorder (SAD), 317;
treatment before Miltown, 127-29. See also benzodiazepines; panic disorder
Asberg, Marie, 72-73
Ashton, Heather, 134-35, 137, 138
AstraZeneca, 174, 302, 324-2 5
Ativan (lorazepam), 18, 140-41, 212 attention
deficit/hyperactivity disorder
(ADHD), 10, 216-29, 325-26 ; ADHD
to Bipolar Pathway, 238, 238 ; bipolar disorder and, 319 ;
case studies,
251-53, 258-60 ; drug therapy, 31-34,
220, 236-38 ; etiology unknown,
220-21 ; hiding the evidence, 309 ; low
dopamine theory, 77-78, 221 ; silencing of dissent, 307. See
also Ritalin
Ayd, Frank, Jr., 64, 151-52
Badillo, George, 20-24, 120, 121
Baldessarini, Ross, 96-97, 158, 160, 184,
188, 191,193-9 4
Banks, Brandon, 200-20 2
Barrow, Jonathan, 255-56
Bayer, 41
Bayh, Birch, 267
Beard, George, 127
benzedrine, 219
benzodiazepine, 28, 29, 126-47, 202,
267-68 ; addiction, 129-30, 140-41 ;
brain damage, 137-38 ; case studies, 139-45 ; disability and,
131, 138 ; fall
from favor, 129-31, 265, 267-68 ;
hiding the evidence, 308-9, 312 ;
long-term effects, 136-38, 159 ;
short-term efficacy, 131, 132-33 ; side
effects, 213 ; withdrawal, 129-30,
133-36, 134. See also Klonopin; Miltown
Berger, Frank, 51-52, 65, 128-2 9
Berrick, Ken, 348-4 9
Biederman, Joseph, 173, 232, 238, 242,
318-19, 319n, 325-26, 325n
Bipolar Child, The (Papolos), 233, 319
bipolar disorder, 14, 17, 172-204 ; academics paid by drug
companies, 323 ; anti-anxiety agents and, 142, 144,
148; antidepressants and, 175-77, 180,
181, 186 ; case studies, 16-20, 24-30,
196-204, 247-60 ; DBSA and, 13;
diagnostic boundaries and, 242, 317-18 ; disability and, 5,
7, 15, 25,
178, 179, 188, 194, 193, 196, 210 ;
drug-based treatment and worsening of, 177, 184-87 ; drug cocktails,
190,
191, 192, 200-202 ; drug side effects,
13, 26, 181, 189-91, 191n; as
epidemic, 179-80, 235 ; etiology unknown, 275 ; Harrow
long-term study, 194-96, 195; hiding the evidence, 307-12 ; juvenile bipolar
disorder, 10, 32, 33, 173, 217, 232-46,
255, 318-19, 325, 325n, 353, 358 ;
lithium and, 175, 182-86, 189-90,
198, 200 ; long-term outcomes, drug vs.
non-drug, 177-79, 185-96, 193, 195;
marketing of, 317-18 ; number of cases, 179, 182, 193,
195-96, 210 ; Patty
Duke and, 174; rapid cycling, 175,
186-87, 199, 237, 239, 243 ; "ultra,
ultra rapid cycling," 243
Blaming the Brain (Valenstein), 61, 78
Blau, Theodore, 270
Bleuler, Eugen, 90
Bockoven, J. Sanborne, 100, 118
Bola, John, 102- 3
Bostic, Jeffrey, 324
Bowers, Malcolm, 71, 75
Boyer, Francis, 58-6 1
Bradley, Charles, 219, 222, 223-24, 233
brain, 61-64, 67-68, 68, 69-70, 69, 77,
80-81, 106-7 ; benzodiazepines and
GABA inhibition, 135-36, 139;
chemical imbalance theory and, 10, 17,
33, 61-64, 70-85 ; damage from
psychotropic drugs, 104, 106-7,
111-12, 113-14, 137-38, 159-60,
170, 189-90, 192 ; Dl and D2
receptors, 75-76, 82, 105, 106, 107,
113, 309 ; Ritalin and, 221-2 2
Breggin, Peter, 230, 284, 287, 304- 5
Briggs, Monica, 24-26, 197
Brinkley, John R., 283-84, 295 Bristol-Myers Squibb, 172,
320n Brodie, Bernard, 61-6 2
Broken Brain, The (Andreasen), 275 Bronowski, Jacob, 3
Buchan, William, 344-4 5
Burke, Tomie, 240
Burns, Geraldine, 139-41, 142
Carlat, Daniel, 313
Carlson, Gabrielle, 234-3 5
Carpenter, William, 100-101, 103-4, 118,
119, 209
Carter Products, 59
catecholamines, 62, 63
Celexa (citalopram), 324
Cha, Jang-Ho, 67
chemical imbalance theory, 10, 17, 33,
61-85, 74n, 264 ; disproved, 77-79, 358 ; marketing of drug
therapy and, 291, 319-20 ; societal belief in, 78
Child and Adolescent Psychopharmacology Made Simple
(O'Neal), 218
children and adolescents: academics paid by drug companies
and, 323-26, 325n; ADHD in, 10, 31-34, 218-29 ; ADHD
to Bipolar Pathway, 238; alternative treatment, 347-53 ;
apathy syndrome, 232 ; case studies, 31-34, 247-60,
313-15 ; delinquency, crime, and mental illness, 227, 257 ;
depression in, 10,
217, 229-32, 318 ; diagnosis of mental
disorders, 10-11, 216-18 ; drug
cocktails and, 32, 33, 173, 244-45,
249, 254, 258, 313-15, 320, 349-50,
353, 359 ; as drug company market,
318-19 ; drug therapy, 31-34, 160-61,
218, 220, 231-32, 238-42, 318 ; drug
therapy, long-term outcomes, 34, 35,
222-29, 243-45 ; drug therapy, side
effects, 32, 222-29, 231-32, 244n,
247-60 ; epidemic of mental illness in, 8-9, 239-46, 241,
246; foster children,
medicating of, 253-57, 347, 348, 357,
359 ; GAO figures on, 246 ; juvenile
bipolar disorder, 10, 32, 33, 173, 217,
232-45, 255, 318-19, 325, 325n, 353,
358 ; lawsuits brought on behalf of, 357 ; number receiving
SSI for mental illness, 3, 8, 241, 245-46, 246, 358 ;
rarity of pediatric mania, prior to drug therapies, 233-3 4
Children and Adults with Attention Deficit Hyperactivity
Disorder (CHADD), 220, 221, 327
Chouinard, Guy, 105-7, 108, 119, 176-7 7
Ciba-Geigy,219, 220
Citizens Commission of Human Rights, 281
Clayborn, Sam, 254-5 6
Clemens, James, 79-8 2
clonidine, 253
Clozaril (clozapine), 250 Cochrane Collaboration, 96n
Cogentin (benztropine), 18
Cole, Jonathan, 95, 99, 104-5, 118,
152-53
Concerta (methylphenidate), 32, 252,
259
Costello, E. Jane, 216
Crane, George, 180
Creation of Psychopharmacology, The
(Healy), 78
DelBello, Melissa, 237, 244, 324-2 5 de Montigny, Claude, 81
Deniker, Pierre, 49-50, 77, 78, 105
Depakote (divalproex), 33, 200, 203, 249,
255,31 5
depression, 68, 68-69, 70, 81-82,
148-71 ; case studies, 24-26, 148-50,
171, 211-12, 214-15 ; in children, 10,
217, 229-32, 318 ; disability and
unemployment, 5, 7, 15, 149, 166,
167-68, 168, 209-1 0 ; drug therapy,
13, 53-54, 162-64 ; drug therapy and
worsening, 157-64, 170 ; drug therapy vs. nondrug outcomes,
153-57,
164-69, 164n, 166, 166n, 167, 362 ;
etiology unknown, 275 ; exercise therapy, 344-47, 346;
hiding the
evidence, 307-12 ; low-serotonin
hypothesis, 71-75, 74n, 77, 289 ; marketing of, 291 ; number
of cases 163-64, 210, 290 ; revision of
diagnosis, 161-64 ; Saint-John's-wort and, 156-57 ; as
self-limiting in nature, 152-53 ; "selling of," 291 ; selling of
Prozac for, 289-9 5
Depression and Bipolar Support Alliance (DBSA), 12-15, 25,
26, 29, 181, 198 ;
drug company alliances, 317-1 8 desipramine, 24, 197
Deutsch, Albert, 44, 91
Dewa, Carolyn, 148, 165-67, 166n, 167
dextroamphetamine, 252
Diagnostic and Statistical Manual of Mental Disorders {DSM),
5, 10, 128,
177, 219 ; / / (DSM-II), 269 ; // /
(DSM-III), 218, 220, 269-70, 271,
295 ; Ill-Revised (DSM-III Rev), 220 ;
IV (DSM-IV), 317
Dobbs, Dorothy, 285-8 6
Domestic Medicine (Buchan), 344-4 5 dopamine, 61, 62, 63-64,
68, 69, 69, 70,
71 ; ADHD and low dopamine theory, 77-78, 221 ; D2 receptors
blocked by
antipsychotics, 75-76, 82, 114 ;
schizophrenia and, 63-64, 69, 70,
75-77, 78 ; supersensitivity psychosis,
105- 7
drug cocktails, 18: for bipolar disorder, 28, 177, 190, 192,
196-97, 200-202 ;
children given, 32, 33, 173, 244-45,
249, 254, 258, 313-15, 320, 349-50,
359 ; iatrogenic illness and, 192,
353-54 ; side effects, 211-1 5
Drugs and the Brain (Snyder), 108- 9
Duke, Patty, 174
Durham-Humphrey Amendment, 56, 57
Effexor, 155, 171,21 3
Ehrlich, Paul, 39-41
electroconvulsive therapy (ECT), 44, 103n, 157, 171, 180-81,
197, 281
Eli Lilly, 42, 47, 172, 187, 320 ; drug revenues, 321-22 ;
drug trials, skewing of, 230-31, 285-86, 288-89 ; fraud
and, 284-85 ; grants and payments to influence opinion, 293,
294,, 317-1 8
327-28 ; lawsuits against, 292 ; Prozac
and, 74, 79-81, 154-56, 239, 284-91,
286n, 292-95, 318, 320 ; Zyprexa and,
208, 301, 320
encephalitis lethargica, 50, 90-91, 219
Epidemiology of Depression, The
(Silverman), 151
Essential Psychopharmacology, 74
Evarts, Edward, 95
Faedda, Gianni, 240, 242, 243
Fava, Giovanni, 159-60, 161, 165, 181
Fieve, Ronald, 182
Fink, Paul, 272
Flugman, Hal, 141-43 fluoxetine. See Prozac Flynn, Laurie,
280, 302
Food and Drug Administration (FDA),
55-56, 94; MedWatch Prozac complaints, 287-88 ; MedWatch
report on Ritalin risk, 236-37 ; Paxil approved for "social anxiety
disorder," 317 ; prescription-only requirement for drugs, 55-56, 56n;
Prozac hearing,
294 ; Risperdal trials and, 300
Ford, Betty, 131
Forest Laboratories, 324
Franklin, Jon, 274, 276
Frazer, Alan, 71, 72, 78
Frazier, Jean, 173
Frazier, Shervert, 290, 298
Freedman, Daniel, 295
Freud, Sigmund, 127, 128, 265
GABA, 135-36, 139
Gately, Theresa, 253-5 4
Geodon (Ziprasidone), 173, 176, 203, 213
Ghaemi, Nassir, 172, 175, 177, 187 GlaxoSmithKline:
academics paid, 322-23 ;
fraud and, 324 ; freebies to psychiatrists, 327; Paxil and,
317, 322,
323-2 4
Glenmullen, Joseph, 78, 284, 307
Gold, Mark, 274-7 5
Good News About Depression, The
(Gold), 274-7 5
Goodwin, Frederick, 175-76, 181-82,
186, 323
Gordon, Chris, 354
Gottstein, Jim, 355-5 7
Grassley, Charles, 322
Gressitt, Stevan, 138
Haarakangas, Kauko, 341
Hagler, Dennis, 14
Hala, Rhoda, 292
Halcion (triazolam), 18
Haldol (haloperidol), 17, 18, 21, 200, 267,
299-30 0
Harding, Courtenay, 109-10, 118, 119, 193n
Harrow, Martin, 115-18, 116, 117, 119,
174-75, 185, 193n, 194-96, 195, 209,
227,310, 310n, 311, 312
Hayes, Inc., 244
Healy, David, 74-75, 78, 230, 283, 284,
305-6, 307, 353
Hellander, Martha, 240
History of Psychiatry, A (Shorter), 4 Hoffman-La Roche, 52,
60, 126, 129,
138
Houtsmuller, Elisabeth, 244
How to Become a Schizophrenic
(Modrow), 333-3 4 Hubbard, L. Ron, 281
Hyman, Steve, 77, 83-84, 85, 222
imipramine, 60, 62, 65, 70-71, 74n, 153,
249, 287. See also tricyclics
Infinite Mind, The (radio show), 323 iproniazid, 53-54, 60,
62, 70-71, 84-85,
180
Jackson, Grace, 356
Jamison, Kay, 28
Janssen company, 299-302, 325
Jenner, Alec, 126
Jensen, Peter, 226, 311
Jones, Barry, 105-7, 108, 119, 176-77
Judd, Lewis, 162, 182, 187, 279, 280, 291
Kefauver, Estes, 56
Kendler, Kenneth, 78-7 9
Kennedy, Edward, 131, 267-6 8 Keropudas Hospital, Tornio,
Finland,
339-44,340, 361-6 2
Kessler, Ronild, 217 Kim, Julie, 3|51
Klein, Rachel, 213-1 4
Klerman, Gerald, 264, 270, 295-96, 298,
304
Kline, Nathan, 47, 53, 65, 153
Klonopin (clonazepam), 29, 141-46, 212,
315
Kraepelin, Emil, 90, 151, 152, 169, 175,
178, 186, 193n, 194, 198
Kramer, Peter, 294
Kuhar, Michael, 276
Kuhn, Roland, 65
Kurtti, Mia, 342
Lader, Malcolm, 133-34, 135, 137-38, 147
Lamictal (lamotrigine), 145, 323
Lappen, Steve, 13, 14, 198-99
Laughren, Thomas, 230
LeFever, Gretchen, 307
Leonhard, Karl, 178
Levin, Cathy, 16-20, 120-21
Lexapro (escitalopram), 145, 324
Librium (chlordiazepoxide), 52, 60, 129,
145
life expectancy, 176, 211, 214-15, 354 Listening to Prozac
(Kramer), 294 lithium, 25-26, 17, 33, 145,175, 182-86,
189, 190, 197, 198, 200, 205, 212
lobotomy, 44, 45, 49, 84, 281
Lord, Nancy, 286-8 7
Luvox (fluvoxamine), 239, 249
Mad in America (Whitaker), 16, 31 On "magic
bullet" medicine, 39-42, 47, 49,
51, 54-61, 65, 78, 84-85, 206-7,
263-6 4
Magic Bullets (Sutherland), 41 Maine Benzo Study Group, 138
Manic-Depressive Illness (Goodwin), 175, 323
Manic Depressive Illness (Winokur), 178 MAOIs (monoamine
oxidase inhibitors),
153,17 1
March of Medicine (TV show), 57, 58 Marks, Isaac, 295, 298
Marsilid (iproniazid), 53, 84
McCulloch, Andrew, 345, 347
McGlashan, Thomas, 100-101,103-4, li 4 McWade, Mathew, 256
Mendels, Joseph, 71, 72, 78
Mental Health (Satcher), 4, 9, 78
mental illness, 353 ; biological psychiatry and, 304 ;
chemical imbalance theory, 10, 17, 33, 61-64, 67-85 ; in children,
5, 10,216-46, 241,246;
deinstitutionalization of patients, 93, 206 ; drugs and
revolutionizing of treatment, 4-5, 9; economics of, after passage of Medicare
and Medicaid, 93, 206 ; epidemic, past 50 years, 5-9, 7,
39-46, 169-71 ; epidemic, social factors, 208-10 ; epidemic
as iatrogenic, 9, 11, 30, 195, 195-96, 205-15,
239-46, 241, 353 ; etiology unknown,
78-79, 220, 332, 358 ; history of
treatment, 12, 42-46 ; hospitalized
mentally ill, 6, 6, 44, 91, 100, 205 ; milieu therapy, 103n;
as self-limiting, 100 ; social policy and, 91-92, 206 ; spending on mental
health services,
328. See also children and adolescents; specific disorders
mental illness, reform of treatment, 331-59 ; Alaska
Project, 355-57 ;
alternative treatment, 43, 332, 335-36 ;
"best" use paradigm, 332, 334-35,
353 ; children and, 347-53 ; David
Healy and, 334-36, 353 ; as
evidence-based, 353 ; exercise therapy, 344-47, 346;
Lapland, open-dialogue
therapy, 339-44, 340; Lapland
need-adapted treatment, 336-39 ; medication withdrawal
programs, 353-54 ; MindFreedom International
hunger strike, 331-33 ; truth in research and marketing,
332-3 3
mephenesin, 51, 52 meprobamate. See Miltown Merck, 41, 55,
60
Miltown (meprobamate), 52, 59, 65, 84,
126, 128-29, 146
MindFreedom International, 331-34, 358
Modrow, John, 333
Moniz, Egas, 49
Moodswing (Fieve), 182
Mosher, Loren, 102-3, 107, 118, 119,
209, 265, 271, 279, 304, 305, 356
M-Power, 18, 148,21 4
Musante, Susan, 357
Myers, Faith, 356
Myers v. Alaska Psychiatric Institute, 356
Myth of Mental Illness, The (Szasz), 264
Nash, John, 204
National Alliance on Mental Illness (NAMI), 174, 302 ; drug
company
alliances, 279-80, 317, 327 ; hiding the
evidence, 311 ; silencing dissent, 305 National Institute of
Mental Health
(NIMH), 46, 153; bias for drug
therapy, 64, 272, 279 ; bipolar child, description of, 237 ;
bipolar disorder, rates, 179 ; bipolar disorder vs. schizophrenia and cognitive
function study, 189-90 ; CATIE Trial, 303 ; Center for Schizophrenia Studies,
271-72 ; chemical imbalance theory, 61-63 ; chronicity of depression and drug
treatment, 158; Collaborative Program on the Psychobiology of Depression, 162,
168; depressed patients and probably outcome,
163-64 ; Depression Awareness,
Recognition and Treatment (DART) program, 279, 289-91, 316 ;
depression study, "naturalistic" outcomes, 167, 168; dopamine
hypothesis, 75, 77; drug
company alliances, 289-91, 295, 298,
299, 316-17, 323 ; Harrow long-term
study of schizophrenia, 115-18, 116,
117, 174-75, 193n, 194-96, 195, 209,
227,310,311,312 ; hiding the
evidence, 307-12 ; Hyman paper, 83-84 ; imipramine trial,
154 ;
low-serotonin theory of depression, 73-75, 74n; marketing of
antidepressants and, 289-91 ;
neuroleptics testing, 94-98, 96n, 118 ; Psychopharmacology Service
Center, 95, 96 ; Ritalin studies, 224, 226-27 ; silencing of dissent, 304-7 ;
Soteria Project and, 271-72, 279, 304 ; STAR*D trial, 163; STEP-BD study,
243-44 ; studies of schizophrenia,
100-102, 101; study of first-episode
psychotic patients, 1946-1950, 92 ;
Thorazine trial, 60-61
National Mental Health Act, 45-4 6 National Mental Health
Association, 327 National Science Foundation, 42 Nemeroff, Charles, 322-2 3
neuroleptics, 4, 14, 50, 61, 64, 89-125,
107, 183 ; American spending on,
yearly, 3; atypical antipsychotics, 13,
14, 15,16, 18, 19,120, 244, 295,
299-302,318,319, 325 ; Bayh
investigation, 267 ; blocking of D2 receptors, 75-76, 82,
113, 114 ; brain
damage and, 104, 106-7, 111-14, 115,
192 ; case for, 95, 96-99, 96n, 108 ; case
studies, 20-24, 121-25, 213-14 ; hiding the evidence, 308-9
; how they alter the course of schizophrenia, 98-104, 101;
long-term outcomes, 29, 89, 98-120,
101, 116, 117, 159, 356, 361-62 ; as
magic bullet medicine, 61 ; MRI studies,
112 ; NIMH trials, 94-99, 96n, 118 ;
paradigm for understanding, 83-84 ; as psychosis-inducing,
64, 82, 99-102,
107, 108-14, 120, 250 ; review of the evidence, 118-20 ;
sales and use of,
320-21 ; side effects, 13, 19, 20, 22, 29,
99,104-5, 107, 108, 111-14, 122,
191, 191n, 211 ; societal belief in,
154-55 ; supersensitivity psychosis,
105-7, 109; unpopularity with
patients, 267 ; used in children, 244,
318, 319. See also Thorazine; Zyprexa
Neurontin (gabapentin), 145, 200
norepinephrine, 61, 62, 68 Norton, John, 278n
Oates, Gwendolyn and Sean, 31-32, 257,
258-6 0
O'Neal, John, 218
One Flew Over the Cuckoo's Nest (film),
264-65, 267
Orr, Louis M., 39
Oxford Textbook of Clinical Psychopharmacology and Drug
Therapy, 223
panic disorder, 295
Papolos, Demitri, 233, 237, 239-40, 242,
243
Parents of Bipolar Children, 240 Pasnau, Robert, 298
Paxil, 149, 155, 314, 315, 317, 322, 323,
334 ; used in children, 323-2 4
Peele, Roger, 272-7 3
peer recovery movement, 24, 26, 148, 214
Pelham, William, 22 7
Pfizer, 41, 57, 172, 176
phenelzine, 153
phenothiazines, 48-5 1
Piatt, Arthur, 268
Post, Robert, 75, 175, 176, 187
promethazine, 48-4 9
Prozac (fluoxetine), 4, 5, 7, 74, 79-82,
80n, 171, 240, 284-91, 286n; children
dosed, 32, 229, 239, 318 ; drug trials,
154-56, 230-31, 285-88 ; Eli Lilly
campaign to save, 292-95 ; fraud and, 284-85 ; lawsuits
against, 292 ; marketing of, 282, 294 ; as model for drug development, 299, 303
; sales
figures, 289, 321 ; side effects, 230,
285-88, 292, 320 ; silencing of dissent, 307; story told in
medical journals, 288-89 ; story told to the public,
289-91, 358
Prozac Backlash (Glenmullen), 78, 307 Prozac Survivors
Group, 292 Pseudoscience in Biological Psychiatry
(Ross), 74
psychiatry, 4, 11, 20, 127-28, 266: academics paid by drug
companies, 276-80, 278n, 288-89, 322-27 ;
"alternative" therapies, 265 ;
antipsychiatry movement, 264-66, 304 ;
biological psychiatry, 63, 263-82, 304 ; categories of
disorders, 128 ; charlatans and, 283-84, 295 ; children, diagnosis
of mental disorders, 10-11, 216-18 ;
critics, discrediting, 280-82, 292-95, 304-7 ; depression,
pre-drug therapy, 151-53 ; diagnostic boundaries
expanded, 209, 242 ; drug-based
treatment paradigm, 4-5, 59-60, 177,
265, 266-76, 270 ; drug company
alliances, 94-95, 276-89, 293-302,
304, 322-27 ; false story told by, 358-59 ; financial
incentives for drug
therapy, 313-28 ; hiding the evidence, 307-12 ; history of
treatment, 3, 4,
42-46 ; "key opinion leaders" (KOLs), 322-26 ;
"magic bullet" medicine and, 263-64, 267 ; marketing of drug therapy,
283-312 ; median earnings, 1970s, 265 ; psychopharmacology
revolution, 4, 47-66, 78, 265, 361 ; rebranding of, 316-21 ;
social psychiatrists, 265
psychopharmacology, 4, 39, 205-15 ; biological psychiatry
and, 263-82 ; development of drug treatment paradigm, 47-66 ; drug sales in
1967, 64 ; drug sales to children promoted, 218 ; expectations for drug
therapy, 64-65 ; financial incentives, 313-28 ;
long-term safety of agents, 65, 211-15 ; "magic bullet"
medicine and, 58-61, 78, 84-85, 185 ; medical-related disability and, 196 ;
paradigm for understanding psychotropic drugs,
83-84, 207 ; Prozac marketing, 288-95 ; psychiatrists
profiting from drugs, 57, 295-302 ; thought experiment, 207-8 ;
Xanax marketing, 295-99, 297 ; "young lady/old
hag" analogy, 205, 206, 361
psychotherapy, 103n PsychRights, 355, 356
Putnam, Robert, 208
Rakkolainen, Viljo, 337, 338, 339
Rappaport, Maurice, 101, 101-2, 107,
118, 119, 209
Recognizing the Depressed Patient (Ayd), 151-52
reserpine, 61-62, 72
Rhone-Poulenc, 48, 49, 51
Risperdal (risperidone), 18, 32, 33, 113,
200, 213, 255, 259, 325 ; biased drug trials, 299-300 ;
marketing of,
299-302 ; side effects, 18-19, 113,
120-21, 301n
Ritalin (methylphenidate), 77, 219, 220,
221-29, 22In, 252 ; case studies,
31-34, 251-53, 255-56; as cause of
juvenile bipolar disorder, 234-38, 241,
242 ; hiding the evidence, 309, 311 ;
risks/side effects, 219, 224-29, 236-38,
252 ; silencing dissent, 306- 7
Robinowitz, Carolyn, 5, 11, 172
Rosenbaum, Jerrold, 293, 304, 307
Ross, Colin, 74
Rubin, Harvey, 273
Sabshin, Melvin, 264, 265, 268, 270, 271,
272, 273, 277
Saint-John's-wort, 156-57
Salo, Tapio, 341, 342
Sances, Melissa, 148-50, 171
Satcher, David, 4, 9, 78, 245
Schildkraut, Joseph, 62-63, 68, 70, 71-72,
78
schizophrenia 63 - 64, 90-91, 109,
112-13, 151, 193, 193n; atypical
antipsychotics and, 295, 299-305 ; case
studies, 20-24, 120, 121-25 ; cognitive impairment in,
189-91 ; discharge rate, 93, 100, 103n; dopamine hypothesis,
63-64, 69, 70, 71, 75-77, 78, 236 ;
drug treatment as psychosis-inducing, 107, 108-14, 192;
disability and
employment, 93, 99, 100, 109-10, 111,
115, 120 ; etiology unknown, 275 ;
Harrow long-term study, 115-18, 116,
117, 174-75, 193n, 194-96, 195, 209,
227, 310, 310n, 311, 312 ; hiding the evidence, 307-12 ; how
antipsychotics alter the course of, 98-104, 101 ; Lapland non-drug treatment,
336-44 ; long-term outcomes drug treatment vs. non-drug, 89, 90, 92-94, 98-120,
101,
103n, 116, 117, 209, 312, 335-36 ;
Mosher's theory of cause, 102 ; MRI studies, 112, 113-14,
119 ; natural history of disorder, 90-94, 92n; neuroleptic risk-benefit
profile, 104-5 ; NIMH drug trials, 94-99, 96n, 118 ;
relapse studies, 97-98, 97n, 99, 104 ;
"revolving door syndrome," 99, 103 ; Risperdal,
marketing of, 299-302 ; short-term drug success, 95, 96n,
97-98, 99 ; silencing of dissent, 304-7 ;
Soteria Project, 102-3, 265, 271-72,
279, 304, 355-57 ; supersensitivity
psychosis, 105-7, 109, 176-77 ; tardive dyskinesia and,
111-12 ; Thorazine and, 92, 93
Schuyler, Dean, 153, 290
Scientology, 280-82, 292-9 5
Scott, Keith, 354
Seeman, Philip, 75, 107, 112-1 3
Seikkula, Jaakko, 339-41, 340, 343,
361-6 2
Seneca Center, 347-5 3
Seroquel (quetiapine), 23, 145, 200, 302
serotonin, 61, 62, 68, 68-69, 71 ;
depression and, 68-69, 70, 71-75, 74n,
289 ; "reuptake" inhibitors, 62, 73, 74,
79-82, 80n
Serzone (nefazodone), 155
Sexton, Scott, 214-1 5
Shader, Richard, 129
Shame of the States, The (Deutsch), 44 Shorter, Edward, 4
Silver, Ann, 120
Silverman, Charlotte, 151
Simon, John, 326
Smith, Jason and Kelley, 33-34, 257-5 8
Smith Kline and French, 57, 58, 59-60,
267
Snyder, Solomon, 75, 108- 9
Solomon, Harry, 100
Soteria House, 102-3, 265, 271-72, 279,
304, 355-5 7
Spitzer, Robert, 269-7 0
Squib, 41
SSRIs (selective serotonin reuptake inhibitors), 74, 79-82,
155-57, 170,
181, 303 ; as cause of chemical
imbalance, 81-82, 170; children given,
160-61,229-32, 238-42, 318 ;
disability and, 167-68, 168; lawsuits
against, 230 ; sales and use, 160-61,
294 ; side effects, 170, 231-32, 305-6 ; silencing of
dissent, 305-6 ; suicide risk, 230, 285, 286, 287, 292, 305-6, 315.
See also Prozac
Stahl, Stephen, 131-32, 192
Stanton, Tony, 349, 350, 352, 353
Stevens, Andrew, 251-5 3
stimulants, 177, 180, 219 ; ADHD to
Bipolar Pathway, 238, 238. See also
Ritalin
Stip, Emmanuel, 89, 98, 118 Stotland, Nada Logan, 172 Stowe,
Zachery, 323
Strober, Michael, 234-3 5
Suavitil (benactyzine), 60
suicide risk, 25, 230, 243, 285, 286, 287,
292, 305-6, 315
supersensitivity psychosis, 105-7, 109,
160, 176-7 7
Supplemental Security Income (SSI) or Social Security
Disability Insurance (SSDI), 6, 18, 206 ; anxiety disorders, 7,
140, 146-47, 209 ; bipolar illness, 142,
196, 199, 256 ; cost of, 10; depression,
149, 209-10 ; "entitlement trap," 208-9 ; number
receiving for mental
illness, 3, 7-8, 210, 241, 245-46, 246,
358
Sutherland, Louis, 41
Szasz, Thomas, 264, 266, 268, 281
tardive dyskinesia, 19, 104, 105, 107,
108-9, 111-12, 304,31 3
Tegretol (carbamazepine), 18
Thorazine (chlorpromazine), 4, 39, 58, 82,
84, 92-94, 105-7, 183, 200, 206, 267 ;
development of treatment, 49-51 ; "magic bullet"
medicine and, 58-59, 206-7 ; NIMH trials, 60-61, 96-98,
96n; rise in disabled mentally ill, 120; side effects, 50,
63, 104-5, 107;
supersensitivity psychosis, 105- 7
Tohen, Mauricio, 187, 189
Tone, Andrea, 132
Touched by Fire (Jamison), 28 tricyclics. See
antidepressants
Upham, Amy, 204, 211-1 2
Upjohn, 131; APA partnership, 316 ; marketing of Xanax,
295-99, 297 ; paid psychiatrists, 295-96, 298
Valenstein, Elliot, 61, 78
Valium (diazepam), 126, 130-33, 134,
145, 147, 149, 303
Van Rossum, Jacques, 64, 70, 75
Vierling-Clausen, Dorea, 27-30, 196-97 Viguera, Adele, 97n
Wagner, Karen, 323-2 4
Wallace Laboratories, 52, 59
Wayne, Kim, 350
weight gain and drug therapy, 13, 29, 122,
140, 191, 203, 207, 214, 244, 249,
250, 301
Weinberg, Jack, 269
Weinstein, Haskell, 57
Wellbutrin (bupropion), 145, 322 Whipple, Edwin Percy, 361
Winokur, George, 153, 178-79, 183, 188 World Health
Organization (WHO):
depression study, 165, 166;
schizophrenia studies, 110-11, 118,
119, 308, 310n, 312 ; Paxil trials, 156
Xanax (alprazolam), 131, 213, 296-97,
297, 298, 303 ; marketing of, 295-99,
297, 303
Zajecka, John, 299, 302
Zarate, Carlos, 187, 189, 311
Zoloft (sertraline), 149, 156-57, 171, 249,
345-46, 346
Zubin, Joseph, 96, 98, 169
Zyprexa (olanzapine), 27, 29, 113, 200,
214-15, 249, 301, 315, 320, 321 ;
marketing, 301-2 ; thought experiment, 207-8 ; weight gain,
13, 29, 214-15,
249, 250, 301
(continued from front flap)
long-term studies—all of which point to the same startling
conclusion—been kept from the public?
In this compelling history, Whitaker also tells
the personal stories of children and adults swept up in this
epidemic. Finally, he reports on innovative programs of psychiatric care in
Europe and the United States that are producing good long-term outcomes. Our
nation has been hit by an epidemic of disabling mental illness, and yet, as
Anatomy of an Epidemic reveals, the medical blueprints for curbing that
epidemic have already been drawn up.
R O B E R T W H I T A K E R i s
the author of Mad in America, The Mapmaker's Wife, and On
the Laps of Gods, all of which won recognition as "notable books" of
the year. His newspaper and magazine articles on the men•
tally ill and the pharmaceutical industry have garnered
several national awards, including a George Polk Award for medical writing and
a National Association of Science Writers Award for best magazine article. A
series he cowrote for the Boston Globe on the abuse of mental patients in
research settings was named a finalist for the Pulitzer Prize in 1998.
ALS O AVAILABL E A S A N EBOO K
Jacket design: LAURA DUFFY
Jacket illustration: DIETRICH MADSEN/GETTY IMAGES Author
photograph: B. D. COLEN
Crow n Publishers Ne w York
4/1 0
www.crownpublishing.co m Printed in the U.S.A.
Exceptional Praise
for
ANATOM Y O F A N EPIDEMI
C
"In making a compelling case that our current
psychotropic drugs are causing as much—if not more—harm as good, Robert
Whitaker reviews the scientific literature thoroughly, demonstrating how much
of the evidence is on his side. There is nothing unorthodox here^thi s case is
solid and evidence-backed. If psychiatry wants to retain its credibility with
the public, it will now have to engage with the scientific argument at the core
of this cogently and elegantly written book."
—DAVID'HEALY, M D, PROFESSOR OF PSYCHIATRY, CARDIFF
UNIVERSITY, AND AUTHOR OF THE ANTIDEPRESSANT ERA AND LET THEM EAT PROZAC
"This is the most alarming book I've read in years. The
approach is neither polemical nor ideologically slanted. Relying on medical
evidence and historical documentation, Whitaker builds his case like a
prosecuting attorney." —CARL
ELLIOTT, M D, PHD, PROFESSOR,
CENTER FOR BIOETHICS, UNIVERSITY OF MINNESOTA, AND AUTHOR OF
BETTER THAN WELL
In
Anatomy of an EpideMic, investigative reporter Robert Whitaker cuts through
flawed science, greed, and outright lies to reveal that the drugs hailed as the
cure for mental disorders instead worsen them over the long term. But Whitaker's
investigation also offers hope for the future: solid science backs nature's way
of healing our mental ills through time and human relationships."
—DANIEL DORMAN, M D, CLINICAL ASSISTANT PROFESSOR OF
PSYCHIATRY, UCL A SCHOOL, OF MEDICINE, AND AUTHOR OF DANTE'S CURE: A JOURNEY
OUT OF MADNESS
"Anatomy of an Epidemic is a splendidly informed,
wonderfully readable corrective to the conventional wisdom about the biological
Jjases——and biological cures—for mental illness. This is itself a wise and
necessary book—essential reading for all those who have experienced, or care
for those
who have experienced, mental illness—which means all of
us!" —JAY NEUGEBOREN,
AUTHOR OF IMAGINING ROBERT, TRANSFORMING MADNESS, 1940, AND
OTHERS
"Every so often a book comes along that exposes a vast
deceit. Robert Whitaker has written that sort of book. Scrupulously reported
and written in compelling but unemotional style, this book shreds
the myth woven around today's psychiatric drugs." —NIL S BRUZELIUS,
FORMER SCIENCE EDITOR FOR THE BOSTON GLOBE AND THE
WASHINGTON POST
"A devastating critique.... On e day, we will look back
at the way we think about and treat mental illness and wonder if we were all
mad. Anatomy of an Epidemic should be required reading for both patients and
physicians." —SHANNON BROWNLEE,
SENIOR RESEARCH FELLOW, NEW AMERICA FOUNDATION, AND AUTHOR
OF OVERTREATED
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