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Robert Whitaker at Massachusetts General, January 2011


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About Whitaker's book "Anatomy of an Epidemic" -- the "Silent Spring of psychiatry?


Do Psych Drugs Do More Long-Term Harm Than Good?

By Carey Goldberg January 19, 2011 NPR/WBUR


It was an explosive question: Might it be that the overuse of psychiatric medications is making many people sicker than they would have been, and preventing their recovery? Are the medications causing an epidemic of long-term psychiatric disability?


And it was about to be debated at a pinnacle of psychopharmacology, the top-rated psychiatry department in the country.


The match had drawn a full house to the fabled “Ether Dome” at Massachusetts General Hospital, the historic medical amphitheater where ether was first demonstrated as an anesthetic in 1846.


.... the two adversaries were about to engage in a “grand rounds” debate — academic medicine’s intellectual equivalent of hand-to-hand combat.


“Thank you,” Massachusetts General Hospital psychiatrist Andrew Nierenberg said wryly, “for coming to the belly of the beast.”


The question is, author Robert Whitaker responded just as wryly, “Will I survive?”


End of humor.... In his new book, “Anatomy of an Epidemic,” Whitaker doesn’t just ask whether long-term medication might often do harm. He presents study after mainstream study that inform his thesis, and he calls for the psychiatry establishment to discuss it openly.


‘The ‘Silent Spring’ of Psychiatry?


A science journalism maven at Harvard told me recently, “Mark my words, this book is going to be the ‘SIlent Spring’ of psychiatry” — a reference to the classic Rachel Carson book that opened the country’s eyes to the harmful effects of DDT.



It is taking [Whitaker] to a national conference on his hypothesis led by psychiatrists and providers of mental health services in Oregon next month. And to a line-crossing move for any journalist: the founding of a non-profit,“The Foundation for Excellence in Mental Health Care,” that will aim to present the science on various psychiatric treatments in a clear and unbiased way.



As the psychiatry establishment goes, this truly was “the belly of the beast”: Massachusetts General’s psychiatry is consistently ranked as the top department in the country by U.S. News and World Report. Sitting at the very front in a dark navy sweater was Jerrold Rosenbaum, the department chair.


Whitaker began with the plot-line about psychiatric drugs that tends to dominate in American society: The introduction of Thorazine in 1955 kicked off a “psychopharmacological revolution” that has included a march of new antipsychotics and antidepressants that are “sort of antidotes to these disorders.” They make it possible to empty institutions, and prevent people from becoming chronically ill. All in all, a positive picture of progress.


Troubling questions


Except that there’s a troubling puzzle: Why, then, did the number of Americans on the disability rolls for mental health reasons triple between 1987 and 2007?


And more troubling questions: Yes, the drugs often help people short-term, and sometimes, longer term. But why do some data suggest that schizophrenics who take anti-psychotics fare worse, long-term, than those who don’t? Why do so many people with depression who take anti-depressants seem to flip into bipolar disorder? And why is the disability caused by bipolar disorder rising so sharply, anyway?


Two of the studies that Whitaker described were particularly striking:


A World Health Organization study [here] found that schizophrenia patients living in poor countries did better long-term than schizophrenics in rich countries. In fact, “Living in a developed country is a strong predictor that a person will never recover from schizophrenia,” he told the audience. “That actually was the study that got me interested in this whole question from the start.”


And a study of 145 psychotic patients over 15 years [here] found that among those who took antipsychotics, only 5% recovered, compared to 40% of those who were off the drugs.


Yes, there could be confounding factors; certainly, patients who were doing better were likelier to go off the drugs. But “I think history is telling you this story,” Whitaker said. “With first-episode patients, you actually want to delay using anti-psychotics, because a significant percentage will get better without needing to go on the drugs, and long-term, you want to try to get as many people off as possible.” A group in Finland began using the medications in that selective way in 1992, he said, and to great success. [That study is here.]


“I don’t think that’s an anti-medication story,” he said. “I think it’s a best-use-of-medication story.”


The refutation


Dr. Andrew A. Nierenberg, director of Mass. General’s bipolar research program and a Harvard professor of psychiatry, disagreed.



In particular, he challenged Whitaker’s numbers on the dramatic rise in the disability rolls, pointing out that according to epidemiological studies, the prevalence of mental illness has remained roughly the same in recent decades. Disability rates, he said, remained similarly stable — even as far more people sought treatment.


“If anything,” he allowed, “We’re realizing over time that our medications don’t work as well as we would like them to in some ways, but I also would assert that it doesn’t cause the amount of harm asserted in the book.”


Getting it ‘backwards’



He directly challenged the 15-year study of schizophrenics. The study’s author himself stated that his findings could be interpreted as meaning that “People who had been doing better said, ‘I don’t want to take this anymore’ and stopped,” he said. To claim that the people did better because they were off medications, he said, ‘is backward.”


As for schizophrenia in poor countries, Nierenberg said, consider a two-year epidemiological study of outcomes among 510 schizophrenics in China. Those who got no treatment did worse in every category than those who did receive treatment, he said.


More: Other longitudinal research that used sophisticated analyses to adjust for the severity of the disorder shows, he said, that among thousands of episodes of depression, patients who got treatment virtually doubled their odds of getting better and cut in half their odds of getting depressed again. And in a half-dozen studies, the longer psychosis went untreated, the worse the outcomes, he said.


The rhetoric ramped up. Nierenberg also accused Whitaker of “gratuitous and misinformed attacks” on the pharmaceutical industry and academia; of denying that mental illness and psychiatry have a biological basis; and of “omitting contradictory data.” Also, “faulty and simplistic reasoning” that “confuses cause and effect.” He said Whitaker “misinterprets outcome studies and comes up with wrong conclusions that end up an indictment of psychopharmacology.”


‘This book contains misinformation’


“The book should have a warning label,” he said: “This book contains misinformation.” We have, he concluded, “a profound disagreement about the data and what it shows.”


Whitaker riposted on several of Nierenberg’s points. On biology, Whitaker said, “It’s not that I don’t believe there are biological causes involved; what I don’t believe is that these drugs ‘fix’ a known chemical imbalance.”


On the Chinese study, he said, the study was skewed because some of its subjects had already been ill for ten years; and “No one is saying that no treatment is a desirable thing. The question is what treatment.”


On depression, Whitaker said, in fact, the untreated group had milder, shorter episodes and one-third the rate of disability of the treated group.


Public trust


As he concluded, Whitaker’s own rhetoric ramped up: “Why do we, as a society, believe that these drugs fix chemical imbalances?” Why do we believe new drugs are better than older ones? “What are the storytelling forces in our society and who do we trust as a population to give us the honest truth? We believe in academic psychiatry,” he said. “We want you to be the arbiters of honest information.” Yet, he said, new drugs get hyped; studies showing negative results don’t get published.


“My appeal here is that we need an honest discussion of the data,” he said. “You’re right,” he told Nierenberg. The end of the book did hold an indictment: “I don’t think academic psychiatry, which had that trust, has honored that trust and been fully open with the public.”


The chief’s belief


No punches pulled. But the hour-long session ended on a conciliatory note. Department chair Jerrold Rosenbaum noted that “We were the place that first began to highlight the risks of treatment discontinuation” — in which patients’ symptoms flare up when they try to go off a drug — “and how to sort that out from relapse. We had our share of criticism from industry and colleagues, and this is still an important question.”


“My belief,” he continued, “is that there are some people for whom Bob’s hypothesis is probably true, and others for whom it’s not, and our challenge is to learn enough about the biology of the disease, the genetic propensities, and be able to predict and match treatments to those patients so we get it right.”


“We are quite primitive now,” he said, “I think you’d all agree with that.”


The last word went to Marlene Freeman, an associate professor of psychiatry in the audience. “Most of us are humbled by what we do every day,” she said. “We do our best to give our patients the most accurate risk-benefit analyses of treatment choices.”


Well-designed studies to really answer the questions you raise are very expensive, she told Whitaker. If you could take some of your passion to the National Institute of Mental Health and get them to fund some of them, “We’d be very grateful.”


Actually, the very last word goes to yours truly....


When I read his “Anatomy of an Epidemic,” I found it highly persuasive — persuasive enough to make me significantly more wary of psychiatric medications — but still just the beginning of a discussion that needs more data to feed it. Judging by the response at the Ether Dome, that debate may be a lively one for a long time.


Whitaker will likely have a role with the new Foundation For Excellence in Mental Health Care, he said, so he may have to give up writing about psychiatry as a journalist. But perhaps he’ll be able to chronicle a transformation in psychiatry toward better long-term outcomes.


“I don’t want to give up writing,” he said. But “if you do have a book that seems to be making an impact, and you do think it’s an important subject that affects lives, you sort of have to go with that.”


Recently, I had the chance to read a beautifully written essay by an MIT student who had been hospitalized, diagnosed with bipolar disorder, and prescribed a variety of drugs that, he writes, caused side effects ranging from kidney problems to extreme paranoia to a general deadening of his curiosity and creativity. When he came upon “Anatomy of an Epidemic,” he writes:


I didn’t think much of it upon first inspection, but ended up reading the entire thing in one sitting. For the first time, I was seeing a thoroughly-researched collection of studies that vindicated my personal experience. I saw dozens of charts, each with at least one data point dedicated to me. The long-term effects of psychotropic drugs were, I learned, largely unknown. This had been mentioned to me in the past, but always as an aside. Whitaker’s message seemed clear and convincing: psychiatric drugs do seem to have a purpose for specific cases, but the current practice of “long-term treatment” may have consequences that do significant harm to the patient.



And here is Robert Whitaker's response to the article, posted as a comment 4 months ago:


This is the beginning of a much-needed discussion. As such, I think it is worthwhile to provide more information about the disability data and studies alluded to here.


1. The disability data


The number of people receiving SSI or SSDI due to mental illness rose from 1.25 million in 1987 to 4 million in 2007. That is a hard number, and it tells of the number of adults 18 to 65 years old who receive government support because they are “disabled” due to mental illness.


Dr. Nierenberg stated, during his presentation, that there had been no rise in disability, over this time, and to support this claim, he cited surveys that looked at the number of people with disabilities of all types—physical, mental, etc.—and said this percentage hadn’t risen. But this was data that included people with physical handicaps, neurological ailments (Alzheimer’s disease, etc.) This is not data that isolates the number of people with “disabilities” due to mental illness. Equally important, this is data that tells of people with disabilities, and not of people who are receiving government support because they are, in government terms, “disabled.”


So, our society needs to ask: Why the extraordinary rise in the number of people on SSI and SSDI due to mental illness?


2. The rise in treatment and the rise in disability numbers from 1990 to 2003.


You quote Dr. Nierenberg stating that disability rates have remained the same even as far more people sought treatment. But, in fact, as the SSI/SSDI data shows, the number of people on disability due to mental illness actually soared during the past 20 years. And after I got home from the Grand Rounds, I realized that Dr. Nierenberg had unwittingly presented data that showed a direct correlation with increased treatment and increased disability.


If you were to look at his slides, you would find that he reported that 29.4% of the American adult population had a psychiatric disorder from 1990-1992, and that 30.5% did in 2001-2003. The prevalence of psychiatric disorders remained the same. What changed was that in 1990-1992 only 20.3% of those with a psychiatric disorder were treated, whereas in 2001-2003, 32.7% were treated. Now if you look up census data for the number of adults in 1990 and 2003, and do the relevant math, you find that the number of people treated rose from 11.16 million adults in 1990 to 21.77 million in 2003.


And what happened to the number of adults receiving SSI or SSDI due to mental illness during that period of increased treatment? It rose from 1.47 million people in 1990 to 3.25 million in 2003.



3. The Harrow Study


I would encourage anyone interested in this topic to really look at the data in this study, and to go beyond the spin that has been put on it. This is the most important long-term outcomes study for schizophrenia that has ever been done, and it is the only study that charts long-term outcomes for medicated and unmedicated patients. As a society, we really need to look at this NIMH-funded study closely.


Martin Harrow is a psychologist at the University of Illinois College of Medicine. From 1975 to 1983, he enrolled 64 adults diagnosed with schizophrenia into the study, recruiting them from two Chicago hospitals, one public and one private. This was a young cohort of patients (median age 22.9 years), and for two-thirds, this was either their first or second hospitalization. In addition, he enrolled 81 others with milder psychotic disorders into his study.


Now, for the next 15 years, Harrow followed the patients and charted their outcomes. He assessed how they were doing at regular intervals (2 years, 4.5 years, 7.5 years, 10 years, and 15 years), and whether they were taking antipsychotic medications. If you dig into the data he reported, in his various tables, and read the study closely, you find that here were the outcomes:


• At end of 15 years, 40% of the schizophrenic patients off antipsychotics (25 of the 64 patients) were in recovery, versus 5% of those on medication. This stark divergence in outcomes appeared by the 4.5 year followup, and remained throughout the study.


• At the 10-year and 15-year follow-ups, only 28% of those off meds suffered from psychotic symptoms, while around 70% of those on drugs remained actively symptomatic.


• At the outset, Harrow also divided his schizophrenia patients into those with a “good prognosis,” based on their internal sense of self, and those with a “bad prognosis.” Starting with the 4.5-year followup and continuing through the 15-year followup, the good prognosis schizophrenia patients off medication had better global outcomes than good prognosis schizophrenia patients on medication, and the bad prognosis schizophrenia patients off medication had better global outcomes than bad prognosis schizophrenia patients on medication.


• Among those with milder psychotic disorders, those off medication—close to half of the cohort of 81 patients-- did much better long-term.


• In terms of all patients, the global outcomes for the patients lined up like this, from best to worst: milder disorders off medication, schizophrenia off medication, milder disorders on medication, schizophrenia on medication.


So what do you see in this data? You see that no matter how you group the patients, those off medication did much better over the long-term. And most startling of all, you see that schizophrenia patients off meds did better longer term than those with milder disorders on meds.


Now, the way that this data has been spun—and frankly, the published articles contains this spin—is that a number of good prognosis patients, having stabilized well on the medication, then were able to get off. That’s the official explanation: the better outcomes reflect a better prognosis, and Dr. Nierenberg, in his quote above, was saying that I had it “backward” to suggest otherwise.


But what I did at the Grand Rounds was report the data, not the spin. And everywhere you look in this study, it was the unmedicated patients who did better. And those with a much more severe diagnosis at the start—the schizophrenia patients—who then got off antipsychotics had a better long-term outcome than those with a milder psychotic disorder who stayed on psychiatric medications. And that is data that needs to be known and its implications discussed.


4. The Chinese Study


As a rebuttal to the many NIMH-funded studies I presented at the Grand Rounds, all of which contradicted the conventional wisdom that people diagnosed with schizophrenia need to be on antipsychotics all their lives, Dr. Nierenberg cited a 1994 study, which looked at patients in a Chinese community with schizophrenia symptoms who had never been treated. (Ran, Br. J of Psychiatry 2001, 178:154-58.)


Here was the design of that study. The researchers went into the community, and identified 510 people with psychotic symptoms. Now 156 of that group had never been treated for their symptoms. This never-treated group had a median age of 48 years, and had been ill for 13 years. And here’s the first important point: This study identified people who had never been treated and who had remained ill. People who had suffered psychotic symptoms in the past and then recovered (without treatment) would not likely have been included in this study.


Now, at that moment of identification, the researchers found that there were 30 people who were on antipsychotic medications and had been taking the drugs regularly. This cohort was younger (35.9 years), and had been ill for a shorter time (7.8 years.) The researchers assessed how these two cohorts were doing at that one snapshot in time, and concluded that those on medications were doing better, on the whole, than the never treated group. They were less likely to have active symptoms, etc.


The researchers then followed the untreated group for two years. They didn’t follow the treated group, and so there is no time comparison at all. And sure enough, this untreated group that had been psychotic for a long time tended to stay psychotic.


You can see the difference between the Harrow study and this study. In the Harrow study, Harrow began following a large sample of patients from early in the course of their illness, and charted their medication use and outcomes. The Chinese study simply reports that a group of chronic, elderly patients who had never been treated stayed chronic. And one final note: 77.6 percent of the chronic patients in the Chinese study were able to do part-time or full-time work. That work rate is far, far above what we see here in the United States.


5. The NIMH’s Long-term Study of Depression


In the article above, Dr. Nierenberg is quoted as stating that in a longitudinal study of depression, those who got treatment virtually doubled their odds of getting better. The study he is referring to is known as the National Institute of Mental Health Collaborative Depression Study, which began in 1998, and it showed no such thing.


In his talk at Grand Rounds, Dr. Nierenberg cited one of the many spin-off studies that have been published form this long-running study of depression. This particular study looked at people who had been treated for an initial episode of depression and then relapsed. The researchers then found that those who were treated for this recurrent episode with a high dose of an antidepressant were more likely to recover from that episode than those treated with a low dose or no drug at all. As much as anything, it was a study designed to assess dosage of antidepressant to be used when people suffer a recurrent episode of depression. (Leon, Am J Psychiatry, 2003, 160:727-33.)


But the key spin-off study from that larger long-running study, which I cite in Anatomy of an Epidemic, is one that looked at the six-year outcomes for depressed patients who were either treated for the disorder, and those who weren’t treated at all. And in that study, 32.3% of those who got treated suffered a “cessation of role function” and 8.6% “became incapacitated,” while only 9.8% of those who didn’t get treated suffered a “cessation of role function,” and only 1.3% became incapacitated. (Coryell, Am J Psychiatry, 1995, 152:1124-29.)


A Need for Discussion


I have posted this long comment because I do truly hope it can be a beginning for a larger societal discussion we need to have. Psychiatric medications can often help over the short-term, and there are people who stabilize well on them for the long term. But in terms of how their long-term use affects long-term outcomes in the aggregate, well, that is a different story indeed. And the soaring SSI and SSDI numbers tell us that we need to look at this “epidemic”, and think what might be done differently.


--Robert Whitaker




This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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