The Antidepressant Era

David Healy, Reader in Psychological Medicine at the University of Wales College of Medicine, has written an extraordinary book, both remarkably clever and amazingly erudite, an unusual combination that has costs as well as benefits. The benefits will be obvious; this is a wonderful read for a psychiatrist. Healy has made dense scientific matters into a page-turning narrative. Everything you ever wanted to know about the biology of depression is set out in lucid, powerful prose. But it is not just the science; it is the leading researchers, their battles, their ideologies, and their ties to the pharmaceutical houses that have become the titans of Wall Street.

This is a social-intellectual history, and Healy is intent on showing the impact on psychiatry of the pharmaceutical houses and the special interest groups within the psychiatric profession. He makes the important point that the drug companies have been selling psychiatry’s new diagnostic categories (e.g., panic disorder, obsessive-compulsive disorder, etc.) as well as the drugs to treat them. Anyone who has gone to an annual meeting of APA in the last two decades will acknowledge that there is something to this thesis. As to the interest groups within psychiatry, Healy emphasizes that they (not just the psychoanalysts) have come together more on ideological grounds than on empirical science.

Healy’s knowledge of psychiatry is extraordinary, and his book goes well beyond the era of depression to chronicle most of the major neuroscientific developments and their impact on twentieth-century psychiatry. For me, Healy is at his best in chapter 5, explaining how the great leap forward in psychiatric science was “as much about artistic verisimilitude as…about scientific exactitude.” Square data were pounded into round holes by the pundits and kept there by the major psychiatric drug companies both for marketing and research momentum. Schildkraut’s catecholamine hypothesis, which Schildkraut himself called a reductionistic oversimplification at best, was accepted as scientific gospel for more than two decades. Healy sums up the psychiatric science of the 1970s: “The major psychiatric disorders became defined as disorders of single neurotransmitter systems and their receptors, with depression being a catecholamine disorder, anxiety a 5HT disorder, dementia a cholinergic disorder, and schizophrenia a dopamine disorder” (p. 163).

Healy believes this oversimplified neurotransmitter “language” supported psychiatry’s transition from dimensional to categorical thinking. Temperament, personality, psychodynamics, culture, social circumstances, and personal misfortune as dimensions of the human experience of depression became relatively unimportant to neurotransmitter psychiatry, which increasingly thought in axis I neo-Kraepelinian categories. At the center of neo-Kraepelinism, Healy places Gerald Klerman, Eli Robins, Donald Klein, Robert Spitzer, and others dubbed an invisible college that produced the DSM-III revolution. Robert Michels is credited with the best critical line about the making of DSM-III: diagnosis in medicine aims “to carve nature at its joints,” as one might disarticulate the Thanksgiving turkey, but the invisible college decided to carve by the feathers (p. 234).

As Healy sees the sequence, biological psychiatry in its reductionistic mode leads to neo-Kraepelinism and that leads to DSM-III and its progeny, each more obsessively categorical than its predecessors. By Healy’s count, we have gone from 180 diagnoses in DSM-II to 292 diagnoses in DSM-III-R to more than 350 diagnoses in DSM-IV. Many psychiatrists, I think, would agree with Healy that we have lost sight of the forest and are counting the trees. As the APA president who signed off on DSM-III, I found many of Healy’s characterizations of its developments in our organization intriguing and enlightening, but some of the details are wrong.

Toward the end of his book, Healy cites the famous remark of Voltaire that history is a trick the living play on the dead (p. 255). Unfortunately, that is the main reservation I have about his book. How many of Healy’s brilliant ironicisms are clever tricks? He challenges established views in every other paragraph, and, although often convincing, sometimes the evidence and the cited studies seem inadequate to support his point. For example, can tricyclics set off a manic episode, as many clinicians believed, according to Healy, on the basis of the catecholamine hypothesis? Healy says no, basing his claim on Angst’s study of medical records before and after the advent of imipramine (1). I agree with Healy that there is a “natural rate of switching,” but I am far from convinced that Angst’s retrospective review of records shows that tricyclics do not lead to a switch. Another example, did “zealous” psychoanalysis do as much harm (“lives mutilated and blighted” [p. 224]) to their patients as lobotomies, regressive ECT, etc.? Healy thinks there is “little doubt that they did,” citing Masson (2) as his sole authority. This seems to me wit without substance, a trick. Part of the problem is that he has aimed his book at general audiences rather than scholars, so it lacks adequate documentation.

Healy also argues as a central thesis that the 1962 regulations of the Food and Drug Administration (FDA) played a crucial role in the direction modern psychiatry has taken. That is an interesting and important idea, but Healy stretches it too far. The amendments grew out of the thalidomide tragedy and locked in place methods for testing safety and efficacy of medications. Conversely, it created the expectation that specific drugs treat particular symptoms. Healy believes that this limits our understanding (his own is extraordinary) of how most of our drugs work and the full range of their effects. True enough, but the FDA does not control the world. Its regulations do not explain why European psychiatry generally took the same positions on treatment and joined the neo-Kraepelinian bandwagon. I think Healy has overestimated the FDA and underestimated the unseemly influence of drug companies over European psychiatry.

The FDA also does not determine which medications will require a prescription in the rest of the world. One needs to point this out because Healy seems to think we might all be better off if patients did not need prescriptions to get medications, as the FDA requires. He is probably right that no patient would have voluntarily taken the harmful megadoses of antipsychotic some psychiatrists gave them, but what about anxiolytics?

I am enormously impressed with Healy’s erudition and intellectual ambition, but I am not sure how much of it he has gotten right. That, I think, is the cost of his cleverness. Nonetheless, this is an important book. If you care about the future of psychiatry as a science or you have been part of its past, read it.

Healy’s publisher, Harvard University Press, has certainly not helped his efforts. There is no bibliography, although the footnotes seem to assume there is one, and parts of the index are inexcusably keyed to the wrong pages.