Answering the Critics: Massachusetts General Hospital Grand Rounds

As many readers of Anatomy of an Epidemic know, I spoke at a psychiatric Grand Rounds at Massachusetts General Hospital on January 13, 2011. In response, Dr. Andrew Nierenberg then gave what he described as a presentation “refuting” the book. Given that Dr. Nierenberg’s presentation occurred within this Grand Rounds environment, it can be seen as an opportunity for academic psychiatry to have presented an “evidence-based” reply to Anatomy of an Epidemic.

As such, it provides a good test for Anatomy of an Epidemic. Did Dr. Nierenberg present data that showed that psychiatric medications improve the long-term course of major mental disorders? Was his presentation well-reasoned? Honest? Did he cite studies in an accurate way? And–since he billed his talk as a refutation of the book–did he present evidence of instances where the book is wrong, as opposed to simply claiming that it is wrong?

I do believe this is an important “debate, for it is ultimately about a question that our society desperately needs to address. Is our drug-based paradigm of care really working? Does it help people struggling with psychiatric distress to get well and stay well? Is there reason to believe that the medicating of children is going to help them grow up into healthy adults?

Grand Rounds is a public forum, and so I am presenting Dr. Nierenberg’s“refutation” of Anatomy of an Epidemic here, along with my replies to his critique. Readers can then assess for themselves the merits of Dr. Nierenberg’s response to Anatomy of an Epidemic.

A. Background to the event.

I received the invitation to give a Grand Rounds presentation last October. It was extremely gracious. I was told that there were members of MGH’s psychiatry department who “spoke highly” of my work, and that I could choose to present on the book as a whole, or some aspect of it for 40 minutes. Dr. Andrew Nierenberg would then “share his perspective” for 10 minutes, which would be followed by 10 minutes of discussion.

In December, I sent the organizers of the Grand Rounds an outline of my talk, which focused on how antipsychotics affected the long-term course of schizophrenia. I said this could serve as a case study of how psychotropics affect long-term outcomes of major mental disorders, which is the larger theme of Anatomy of an Epidemic. I provided a list of citations for 35 or so studies that I would cover, and said that I would also show a handful of slides related to Martin Harrow’s long-term study of outcomes for people with schizophrenia and other psychotic disorders (which I also sent to the organizers.) This is the material that is covered in chapter six of Anatomy of an Epidemic (“A Paradox Revealed.”) I was simply going to present it in an academic style.

I then waited Dr. Nierenberg to send me an outline of his presentation, thinking that it would be a response to the talk that I was going to give. Two days before the scheduled Grand Rounds, he sent me his slides for his presentation, which was titled: “A Refutation of Anatomy of an Epidemic.”

I was now asked to keep my talk to 30 minutes. Dr. Nierenberg was allotted close to that amount of time, with a few minutes then left for discussion.

B. Dr. Nierenberg’s disclosure statement.

Dr. Nierenberg did not send me his disclosure statement in the slides he sent me; however, this is information about his ties to pharma that he has disclosed in other forums.

He has served as a “retained consultant” for the following companies: Abbot Laboratories, AstraZeneca, Basilea Pharmaceutica; Brain Cells, Bristol-Myers Squibb, Eli Lilly, Epi-Q., Genaissance Pharmaceuticals,  GlaxoSmithKline, Innapharma, Janssen Pharmaceutica, Jazz Pharmaceuticals, Merck, Novartis, Pfizer, PGxHealth, Schering-Plough, Sepracor, Shire, Somerset Pharmaceuticals, Takeda Pharmaceuticals, and Targacept.

He has received grants/research support from Bristol-Myers Squibb, Cederroth, Cyberonics, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceutica, Lichtwer Pharma, Pfizer, Shire, and Wyeth-Ayerst Laboratories.

He has been a member of the speakers’ bureaus for Bristol-Myers Squibb, Cyberonics, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Shire, and Wyeth-Ayerst Laboratories.

C. Dr. Nierenberg’s presentation:

Part one:  Slides 1-5

In this opening set of slides, Dr. Nierenberg promises to “refute”  and “repudiate” Anatomy of an Epidemic. As for Paul Krugman’s quote on slide five,  I believe that his point was that I must be either filled with malice toward psychiatry or ignorant. This, of course, is known in debate circles as an ad hominem argument.

Part two: Has the number of adults disabled by mental illness increased during the modern era?

Dr. Nierenberg’s slides 6-15

Here, Dr. Nierenberg is making his first “data-based” argument, which consists of two parts. One, he is stating that there has been no rise in the number of people “disabled” by mental illness during the past 50 years (on a per-capita basis), and that disability rates in particular have stayed stable in the past 20 years. Two, he is asserting that even though the number of people treated for psychiatric disorders rose between 1990 and 2002, there was no rise in the disability rates for people with mental illnesses. If treatment increased the risk of disability, as was claimed in Anatomy of an Epidemic, then there should have been a rise in the disability rates.

This is a key issue, and if Dr. Nierenberg’s assertion is true–that there was no rise in the number of people “disabled” by mental illness between 1990 and 2003–then Anatomy of an Epidemic is indeed a deeply flawed book. So let’s go through the evidence I presented in the book, and then take a look at the studies he cites. The beauty of this exercise is that, when we are finished, we will see that within this set of slides, there is powerful data that helps support the thesis of Anatomy of an Epidemic.

In Anatomy of an Epidemic, I traced the number of adults under government care due to mental illness from 1955 to today. In 1955, there were 355,000 adults in state and county mental hospitals with a psychiatric diagnosis, a disability rate of 1 in every 468 Americans. Over the next 30 years,  the United States sought to empty its state hospitals and care for the “disabled” mentally ill in the community, with people so disabled  receiving a SSI or SSDI payment from the federal government. In 1987, there were 1.25 million adults receiving an SSI or SSDI payment due to a mental illness, or 1 in every 184 Americans. In 2007, there were 3.97 million adults on SSI or SSDI due to mental illness, or 1 in every 76 Americans.

Now, in Anatomy (page 7), I noted that comparing the hospitalized mentally ill to those on SSI and SSDI may be “an apples to oranges comparison.” But the SSI and SSDI numbers from 1987 to 2007, I observed, is an “apples to apples” comparison. And this is very focused data: It tells of the number of adults, 18 to 65, who received a federal disability payment because they were “disabled” by a psychiatric illness during those years. And this number tripled between 1987 and 2007.

I should note that others have used the SSI and SSDI data to track the increase in the number of people disabled by mental illness. E. Fuller Torrey did so in his 2001 book The Invisible Plague, and he noted that this number provides an undercount of the true number of adults disabled by mental illness in our society because it does “not include individuals in state mental hospitals, those receiving Veterans Administration benefits, and those who were homeless or in jail and who had not applied for such benefits.”

So what is the basis for Dr. Nierenberg’s assertion that “disability rates (for psychiatric disorders) are stable?” Go to the slides titled, “Disability Definition,” “Overall Disability Rates: All Causes,” and “Prevalence of those With Depressed or Anxious Symptoms that Seriously Interfered with Function.” This is data from the U.S. Census Burea presented in periodic reports titled “Americans With Disabilities.” Dr. Nierenberg is describing this data as though it is a count of people with a mental illness, but, in fact, these reports tell of people living with disabilities of all types–people using wheelchairs, or on crutches; people with vision and hearing impairments; people with mental retardation; people with Alzheimer’s disease, and so on. Those with a mental illness or emotional disorder are simply a subgroup of this larger categorization of Americans living with a disability. Moreover, this isn’t even data of people on government disability, but rather simply people living with a disability of some type, with the overwhelming majority not on government disability.

In other words, Dr. Nierenberg–with his presentation of the U.S. Census data in a misleading way–is trying to trick the audience into thinking that there has been no increase in the number of disabled mentally ill, particularly during the modern era, when use of psychotropic drugs has exploded.  But the SSI and SSDI data, which is the relevant data, tell otherwise.

And now let’s go into a second set of data that Dr. Nierenberg presented in this set of 10 slides. Look at the slides titled “Stable Prevalence of Psychiatric Disorders” and “Prevalance Stable Despite Increased Rates of Treatment.” Those slides state that about 30% of the adult population suffered from a psychiatic disorder in 1990-1992, and that a similar percentage did in 2001-2003. However, whereas only 20.3%  of those with a psychiatric disorder were treated in 1990-1992, 32.7% were treated in 2001-2003. When carefully examined, this data provides powerful support for a principal theme in Anatomy of an Epidemic, which is that psychiatric medication are fueling the epidemic of disabling mental illness that has erupted in our society.

If  you look up census data for the number of adults in 1990 and 2003, and do the relevant math (based on the survey data that Dr. Nierenberg cited,) you find that the number of people treated rose from 11.16 million adults in 1990 to 21.77 million in 2003. And here’s the key: The number of  people receiving SSI or SSDI due to mental illness during this period more than doubled, from 1.47 million people in 1990 to 3.25 million in 2003.

There is one other way to  parse this data. In 1990, there were 55 million adult Americans with a “psychiatric disorder” (based on the prevalence data cited by Dr. Nierenberg.) There were 1.47 million adults who collected a federal disability check that year due to mental illness. Thus, one in every 37 (2.7%) adults with a psychiatric disorder in 1990  was on long-term disability. By 2003, the adult population had increased, and thus although the prevalence of psychiatric disorders had remained the same as in 1990, the number with a psychiatric disorder had risen to 66 million. There were 3.25 million  adults who were collecting a federal disability payment that year due to mental illness, or one in every 20 with a psychiatric disorder (5%). Thus, during this period of markedly increased treatment, the percentage of those with a psychiatric disorder who ended up on long-term disability rose from 2.7% to 5%.

I wish I had come up with this specific data while researching and writing Anatomy of an Epidemic. In attempting to “refute” Anatomy of an Epidemic, Dr. Nierenberg provided powerful data supporting a primary theme in the book, which is that our drug-centered form of care is fueling an epidemic of disabling mental illness.

Part three: Have the biological causes of mental disorders been found?

Dr. Nierenberg’s slides 16-20

In his opening slides, Dr. Nierenberg stated that I had asserted in Anatomy of an Epidemic that there is “no biological basis for psychiatry.” Having set up that straw-man claim (that’s not what I say in the book), he now “refutes” it.

As readers of Anatomy know,  what I report on in the book is the rise and fall of the “chemical imbalance” theory of mental disorders. There is nothing that Nierenberg presents here that “refutes” that part of the book. Indeed, as Dr. Nierenberg and others at the Grand Rounds admitted, the “chemical imbalance” story is an “outdated model.”

I personally believe that there may be biological factors involved in many psychiatric disorders. (I also believe that trauma and other social experiences underlie a lot of psychiatric distress.) But my point in Anatomy of an Epidemic is that the biological causes of mental disorders remain unknown, and thus there is no clear biological target for drug development. And it would take a whole new book to assess the significance of the “multiple dysregulations” that are now said to be associated with psychiatric disorders, and assess too whether those dysregulations are seen in unmedicated patients long-term, or only in medicated patients.

Finally, one small note. As for the quote from Anatomy that is on the second slide in this set, Dr. Nierenberg changed the tense of one verb and also left out a word (in other words, it’s not accurate.) I am not sure why he chose to do this. This quote is from a part of the book in which I’m tracking the “rise of an ideology” within psychiatry in the 1980s, and I am observing that, at that point, the first-generation psychiatric drugs had lost their luster. Here’s the actual quote: “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 for Dr. Nierenberg’s reference to Spinoza, circa 1650, here he is telling the audience that my understanding of the brain is stuck in the dark ages.

Part four: How do antipsychotics affect the long-term course of schizophrenia and other psychotic disorders?

My talk at the MGH Grand Rounds was focused on this question. I reviewed the long-term outcomes literature from 1960 until today, which, I argued, led to one of two possible conclusions:

1. At the very least, there is a significant percentage of people diagnosed with schizophrenia or other psychotic disorders who can do well long-term off medication (better than if they were medicated.)

2. In the aggregate, antipsychotics worsen the long-term course of psychotic disorders.

I concluded my presentation with a short slide presentation of the data from Martin Harrow’s 15-year study of schizophrenia outcomes, and a brief look at a program in northern Finland that uses antipsychotics in a selective, cautious fashion and is producing very good long-term results.

Here are my slides.

In his published article, Martin Harrow presents his findings in this context: There is a cohort of schizophrenia patients with a good prognosis who, after stabilizing on antipsychotics, are able to get off the medications and do well over the long-term. In Anatomy of an Epidemic, I quote Harrow to this effect. (P. 217). However, the data in his study belies that “meds are good” explanation. Instead, his data supports the notion that antipsychotics worsen the long-term course of psychotic disorders (in the aggregate.)

From 1975 to 1983, Harrow enrolled sixty-four young people diagnosed with schizophrenia into his study, recruting them from two Chicago hospitals. One was private and the other public, as this ensured that the group would be economically diverse. He also enrolled 81 young people with milder psychotic disorders. All of these patients were treated conventionally with medications in the hospital, and then Harrow tracked their long-term outcomes, periodically assessing how they were doing. Were they symptomatic? In recovery? Employed? Were they taking antipsychotic medications. And here is what his data shows:

1. The 25 schizophrenia patients who got off antipsychotic medications had much better long-term outcomes than those who stayed on the drugs. (See slides 2, 3, 4, 5, and 6.) The off-antipsychotic patients had an eight-fold higher recovery rate; their aggregate global outcomes were much better; they were much less likely to have a “uniformly poor outcome;” and they were much less likely to still have psychotic symptoms at the 10-year and 15-year followup assessments.

2. Among the 81 patients with milder psychotic disorders, those who stopped taking antipsychotics and other psychiatric medications (nearly half of the cohort) had markedly better global outcomes than those who stayed on the medications. (Slide 7).

3.  The collective outcomes for all of the psychotic patients stacked up like this, from best to worse: milder psychotic disorders off meds, schizophrenia off meds, milder psychotic disorders on meds, and schizophrenia on meds. In other words, those with a milder disorder at the beginning who stayed on meds did worse long-term than the schizophrenia patients who got off the medications. (Slide 8).

4.  Finally, Harrow grouped his schizophrenia patients into good-prognosis and bad-prognosis patients at the beginning. While he didn’t provide the specific outcomes data for each group, he did observe that in each of these two sub-groups, it was those who got off antipsychotics who had better long-term outcomes. (Slide 9).

Now this is the only study of its type in the outcomes literature, in which a researcher has followed a large cohort of patients over a long period of time, and assessed both their medication usage and outcomes. And it belies the common wisdom that all people diagnosed with schizophrenia and other psychotic disorders need to be on antipsychotics all their lives, and–at least in my opinion–it also provides evidence that, over the long-term, antipsychotics are agents that worsen global outcomes for people with psychotic disorders.

Given Harrow’s findings, then you would think that a protocol that sought to mimize long-term use of the medications would produce better outcomes. In western Lapland, which is a district in Northern Finland, the psychiatric community adopted such a protocol in 1992, and the long-term outcomes of their psychotic patients are now by far the best in the Western World. (Slide 10).

Dr. Nierenberg’s reply: Slides 21-25.

In his reply to this part of my book (and talk,) Dr. Nierenberg focused on discrediting the Harrow study and the Finnish report on its outcomes. Then he presented data from a study meant to show that antispychotics improve long-term outcomes.

In regard to Harrow’s study, Dr. Nierenberg argued that it was a retrospective study, that it wasn’t randomized, and that the results can be explained by a “propensity analysis,” i.e. this is just a story of those with a better prognosis who, after stabilizing well on the meds, got off the meds.

Now let’s look at all three of his criticisms. First, Harrow’s is not a retrospective study, but a prospective study. This is the opening line in the  abstract: “This prospective longitudinal 15-year multifollow-up research studied whether unmedicated patients with schizophrenia can function as well as schizophrenia patients on antipsychotic medications.”

Second, the randomization issue is a straw-man complaint. There is no possible way to run a 15-year randomized study in which you keep one group of patients on the medications throughout this time and the other group continually off the drugs. No institutional review board would approve such a study. In the Harrow study, everybody was conventionally treated in the hospital with medication, and then their long-term outcomes were periodically assessed. I do not know how you could better design a long-term outcomes study.

Third, Harrow’s results do not just tell of patients with a better prognosis who, after stabilizing well on the meds, got off the meds and then did better than patients with a bad prognosis (which is what Dr. Nierenberg argued.) The published article did put that spin onto the results, but that is not what the data actually shows. In each subgroup of patients, those off medication did better than those on medication, and those who were more seriously ill at the beginning (the schizophrenia patients) who got off meds did better long term than those with a milder illness who stayed on psychiatric medications. At the very least, this belies a quick explanation that this is just a story of “good prognosis” patients getting off the medications. Antipsychotics do affect the long-term course of people’s lives, and everywhere you look in this study, the patients who stayed on the medications fared poorly (as a group.)

As for the Finnish report on its five-year outcomes, Dr. Nierenberg’s argument is that the researchers did not do a “propensity analysis,” which would assess whether it was those with a better prognosis or a milder illness who did well without medications. But this is an argument that has no relevance to the Finnish reports on open-dialogue therapy. The Finnish investigators are not studying the outcomes of medicated vs. non-medicated patients treated with open-dialogue therapy; they simply are reporting the five-year outcomes of all first-episode patients with a particular model of care that emphasizes selective use of antipsychotics.

Finally, Dr. Nierenberg cites a study of outcomes of  people with schizophrenia in China as evidence that antipsychotics improve the long-term course of schizophrenia. This is his counter study to the long history of research that I reviewed in Anatomy of an Epidemic (and reviewed in my Grand Rounds talk), and thus this study apparently should trump that research in terms of the governing “evidence base” for the use of psychiatric drugs.

The Chinese study is difficult to understand. But here is what I think happened. The researchers interviewed all of the heads of households in a rural Chiniese community of 149,231 people, and thus identified 510 people with schizophrenia. Of this group, 156 had never been treated. This never-treated group, with a mean age of 48, had been sick on average for 13.6 years. Now, among the 510 people identified with schizophrenia, there was a second group of 30 that had been regularly taking antipsychotics. This antipsychotic-treated group, with a median age of 36, had been sick on average for 7.8 years. And at baseline–that is to say, when the researchers first interviewed these two cohorts of patients (which are of different ages and had illnesses of different lengths) — the drug-treated group was more likely to be asymptomatic, or in partial remission than the never-treated group. (Table 3.) This is the data that Dr. Nierenberg presents in his slide, although he labels it as “two-year” outcomes data, but it is actually baseline data.

The researchers then “followed all the patients who had never received treatment for 2 years.” In other words, this study only follows a chronic group of older patients who had never been treated, and then they assess how this untreated group did during that time. And perhaps not surprisingly, 82% continued to have marked symptoms. (However, 78% still did “full or part-time work,” which is an employment rate far superior to drug-treated schizophrenia populations in the U.S.)

In Anatomy of An Epidemic, I certainly did not argue for “no treatment” as a preferred option for schizophrenia patients. The question posed by my review of the outcomes literature is whether there are non-drug forms of treatment that might be preferable to medications, and the effect of medications on long-term outcomes in the aggregate. So this study doesn’t address that question of whether other forms of treatment might be superior to drug treatment. In addition, this study gives a skewed picture of the outcomes for “never-treated” patients. If someone in this rural Chinese community had suffered a bout of psychosis five years before the researchers showed up and then recovered without any drug treatment, that person very likely would not have been identifiedy in the cohort of 510 people with schizophrenia in the village.  This study basically identified a group of never-treated patients who had been ill for some time and followed them for two more years, and found that most remained psychotic.

So that is the study that, in Dr. Nierenberg’s presentation, is expected to trump the findings by Martin Harrow and the many other NIMH-funded studies I reviewed in Anatomy of an Epidemic. And all I can say is this: If this Chinese study is indeed seen as more significant than Martin Harrow’s, then I would suggest that the American public stop funding NIMH outcomes research, because apparently the research being funded by that federal institute  is close to worthless.

Part Five: How do antidepressants affect the long-term course of depression?

Dr. Nierenberg’s slides 26-29.

I did not speak at any length about antidepressants in my presentation. But in this set of slides, Dr. Nierenberg is responding to chapter eight of Anatomy of an Epidemic, which tracks how, during the antidepressant era, depression has been transformed from an episodic disorder, with pretty good long-term outcomes, into a much more chronic illness, marked by increased rates of disability. And in these slides he presents data that, at least at first glance, suggests that in a long-term 25-year study, drug-treatment increased the likelihood of recovery.

Here’s the context for this particular study. From 1978 to 1981, the NIMH Collaborative Depression Study recruited 955 subjects who sought treatment at a hospital for one of the major affective disorders. Over the next two decades, NIMH-funded researchers conducted many studies of this population. In the Leon study cited by Dr. Nierenberg, researchers were studying 285 patients with major depressive disorder who, at some point during the 20 years, suffered a recurrence of depression. These 285 patients had been treated with antidepressants, and many were taking antidepressants when they suffered a relapse. And what the researchers studied in this particular case was whether those who had suffered a relapse should be treated with a high dose of an antidepressant, a medium dose, or a low dose. They found that the recovery rate from that recurrent episode, over a short period of time, was higher for those given a high dose, and that apparently a medium dose was also better than no somatic treatment (although the study doesn’t provide any information about that no-treatment group, and so it is unclear how that comparison was made.)

Thus, this study cited by Dr. Nierenberg doesn’t provide any information on the long-term outcomes of depressed patients who take antidepressants versus those who eschew such treatment. However, NIMH investigators leading the Collaborative Depression  research effort did conduct such a study, which I reported on in Anatomy of an Epidemic (page 167.) They studied 547 people who suffered a bout of depression, and they found that over the course of six years, 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 shoter-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,” the researchers wrote in their 1995 report.

In short, Dr. Nierenberg picked a short-rerm dosage study from this large NIMH research effort to assert that antidepressants improve the long-term outcomes of depressed patients. He ignored the actual study from that same research program that assessed six-year outcomes of treated and untreated patients, and had found that the untreated patients fared remarkably better.

Part Six: The rest of Dr. Nierenberg’s slides.

In the final part of his presentation, Dr. Nierenberg objects to my reporting on the ties between pharmaceutical companies and academic psychiatrists. He then concludes with a slide showing the cover of Anatomy of an Epidemic with a black box warning underneath,  stating that reading my book can be hazardous to your health.

In Anatomy of An Epidemic, I do write  about the ties between pharma and academic psychiatry, and my focus is on how those ties  have  created a story-telling apparatus that regularly misleads the public. The public has been led to believe that psychiatric drugs fix chemical imbalances in the brain, like “insulin for diabetes,” even though research did not find that to be true. The public was told that the second generation psychiatric drugs were so much better than the first generation, when the research did not show that to be so. And time and again, the results from long-term studies that told of better outcomes for unmedicated patients have been kept hidden from the public.

In Anatomy of an Epidemic, I also detail how the powers that be have sought to discredit those who challenged the common wisdom, deriding them as flat-earthers and so forth. And I think, if you review this presentation by Dr. Nierenberg, you will see many of those storytelling forces at work.

Postscript: My WBUR debate with Dr. Nierenberg

Six days after that Grand Rounds, Dr. Nierenberg and I appeared together on an afternoon radio show to debate these issues. That experience was rather frustrating, as it is difficult to counter accepted wisdom in 30-second soundbites. A link to the radio show was then posted on the WBUR website. In the accompanying blurb, I was described as a “local journalist and author,” which is fine. And then this: my claims are “refuted by reputable members of the psychiatric community here in Boston.”

Refuted . . . proven to be false. And, by going through these slides, readers can assess the intellectual merits of that “refutation” of Anatomy of an Epidemic.