Review by Daniel Herman*

There is broad agreement among clinicians that while our current medications are not fully effective, their widespread use has enhanced health and quality of life for people with a mental illness. Consensus argues that while negative side effects can be a significant problem, these are generally outweighed by a reduction in disabling symptoms. Therefore, most believe, long-term outcomes for persons with mental illness in the US and other parts of the industrialized world are better now than they have ever been.

In his latest book, Anatomy of an Epidemic, award-winning journalist Robert Whitaker raises a disturbing question: if our psychiatric treatments are truly effective, why aren't people with mental illness doing better? He argues that long-term outcomes are worse than ever, and that this state of affairs can be largely attributed to the widespread and rapidly expanding use of psychiatric medications. He says they create functional disability and severe iatrogenic complications. In short, he turns conventional wisdom upside down.

How it can be, Whitaker wonders, that the proportion of American disabled by mental illness has risen so dramatically during this era of modern psychiatry? He cites as evidence data showing the proportion of Americans receiving SSI and SSDI due to psychiatric disability grew from 1.25 million (1 per 184) in 1987 to 3.97 million (1 in 76) in 2007. Whitaker augments this line of argument with epidemiologic studies of the course of illness in persons with psychosis in the US and in developing countries, where widespread psychopharmacologic treatment is not typical, suggesting that persons in the developing world experience, on the whole, better outcomes than in the United States. The well-known World Health Organization collaborative International Study of Schizophrenia found, for example, that persons in poor countries diagnosed with schizophrenia enjoyed significantly better outcomes in a broad variety of domains including symptoms, disability and social functioning.

Longitudinal studies of persons with schizophrenia in the United States permit comparisons between persons with varying exposure to antipsychotic medications. Here, again, Whitaker aims to demonstrate that more use of medication is associated with poorer outcomes. Although much of the evidence that he presents concerns psychotic disorders, Whitaker also focuses on anxiety, depression and bipolar disorder as well as childhood disorders such as ADHD.

It is this apparent paradox--more treatment and worse outcomes--that is the essence of the problem Whitaker aims to illuminate. He argues that the main driver of these adverse outcomes is the very treatments that the current consensus claims should mitigate these disorders. Noting that antipsychotics, antidepressants and other psychotropic drugs all operate by effecting neurotransmitter functions in the brain, Whitaker agrees with the scientific community that changes resulting from exposure to these agents reduces selected symptoms. It is the long-term exposure to these agents, he argues, that frequently leads to impaired functioning caused by adaptation of the brain to this altered neurochemical environment. Chronic exposure to psychotropic medications makes the brain function "abnormally" he argues, leaving people worse off than they might otherwise have been without the treatment. This claim, even if true for only a minority of persons receiving treatment, clearly would have dramatic implications for patients and professionals alike.

The strong reaction to this book is a story in itself. Controversy has raged all around, from reviews that consider his arguments to be "worryingly sane and consistently based on evidence" to those harshly critical of Whitaker's facts and conclusions. Whitaker's very appearance in professional gatherings has stimulated considerable controversy. At a SAMSHA-sponsored national conference in San Diego last year, he was first invited, then disinvited, then re-invited to deliver the keynote address. In Boston, he was confronted by Andrew Nierenberg, a clinical researcher who refuted his conclusions and who accused Whitaker of "gratuitous and misinformed attacks" on both the pharmaceutical industry and academic psychiatry and suggested that the book should include a warning label, saying "This book contains misinformation." He and Whitaker have tangled before. A somewhat more balanced assessment came from Dr. Dan Carlat, an author and psychiatrist who regularly blogs about ethics, conflicts of interest, and errant psychiatrists. An essay by another practicing psychiatrist was distributed to the assembly of the APA saying it had caused her "professional turmoil and consternation," and forced her to rethink many of the principles with which she was trained about family and community involvement, and to listen to more carefully to patients. To date little has appeared in the professional journals, whether by design or the notorious lag time for disseminating information in psychiatry, especially when the essence of their work is being put under a microscope.

Critics accuse Whitaker of failing to acknowledge other explanations for apparently increasing numbers of persons disabled by mental illness. Changes in federal disability insurance policy, they argue, contribute to this. They also argue that Whitaker confuses association with causation. Specifically, he interprets studies demonstrating poorer outcomes among people with histories of more psychotropic treatment as evidence for the deleterious effect of the treatment when it may simply reflect the fact that persons with more severe and chronic conditions tend to receive more treatment.

The association-causation conundrum is also relevant to Whitaker's claims that the significant brain differences observed between healthy people and those with severe mental illnesses (such as reduced gray and white matter volume in persons with schizophrenia, for example) are evidence, not for the impact of the disease process, but rather for the adverse impact of the medications used to treat the illness. This has proved to be a difficult question to study. A new paper by a prominent research psychiatrist, Nancy Andreasen and colleagues lends some credibility to the argument as do the conclusions of a recent comprehensive research synthesis on this question. However, it is also important to note that even if future research were to confirm the association between exposure to antipsychotic medication and reduced brain volume, it is not clear that these modest reductions necessarily correlate directly with impaired functioning in persons with schizophrenia.

Ethical concerns have largely constrained contemporary researchers from carrying out studies that would provide the most compelling evidence on questions critical to Whitaker's assertions. The design of the NIMH-sponsored RAISE study, in which I am a member of a team currently examining treatment for first episode psychosis, does not permit a systematic test of the impact of a no medication or delayed medication treatment strategy. However, there may be signs of movement in the way in which the psychiatric research establishment views this issue. A newly-launched Australian trial will vary treatment regimens to determine the impact of delaying the introduction of medication in some cases of psychosis.

It is important to note that while Whitaker aims to raise the alarm about the potential adverse effects of psychiatric medications, he's no Scientologist. He does not reject the entire psychiatric enterprise nor does he advocate that persons with mental illness should necessarily stop using medications. Whitaker acknowledges that medications may indeed alleviate symptoms and, for many, are indispensable elements in the process of long-term recovery. He argues for more judicious use of medications and close monitoring of adverse outcomes as well greater emphasis on the provision of empirically supported psychosocial interventions. In fact, this aligns well with current best-practice guidelines promoted by psychiatric experts.

Whitaker's unsettling thesis is certainly worthy of careful consideration and serious debate. The history of medicine and psychiatry in particular is replete with broadly accepted and applied treatments that were later found to be ineffective or harmful. Cynicism is apt to continue to grow as a result of ongoing revelations showing close ties between powerful commercial interests that develop and promote drugs used to treat psychiatric disorders and many of the investigators who evaluate them, making it critical that claims like Whitaker's are seriously considered. The need for well-designed research to provide solid evidence refuting or supporting his claims is clear.

*Daniel Herman, DSW, MS, is the Director of the ACT Institute for Recovery-Based Practice in the Center for Practice Innovations at New York State Psychiatric Institute where he is also an investigator in the Division of Mental Heath Services and Policy Research. He is an Associate Professor in the Department of Psychiatry at Columbia University.

email: dbh14 [at} columbia.edu