Before Prozac

by Edward Shorter
Oxford University Press, 2008
Review by S. Nassir Ghaemi, M.D., M.A., M.P.H. on May 19th 2009

The field of history of medicine, prior to the mid twentieth century, was largely an antiquarian's delight, devoted mostly to showing the inevitable progress of medicine. In that sense, it was a reflection of the meliorist, evolutionary ideology of the late nineteenth century. Two world wars shook that confidence, and, especially in post war France, history of medicine was reborn as part and parcel of the postmodernist movement, an approach to culture that involved a deep rejection of the Enlightenment tradition. Ironically that a founding tome of the postmodernist movement was a book on the history of psychiatry (Foucault's famed work Madness and Civilization). It followed that history of medicine (and history of psychiatry more specifically) became a largely postmodernist discipline: where there had been order, there was now Brownian motion; where progress, regression; where logic, power; where reason, money. The new histories of medicine, especially from the 1960s onward, reflected this revisionism, and the corresponding academic journals today, like History of Psychiatry, would automatically reject, with disdain, any paper that dared breathe the word "progress." The old catechism has become the new heresy; the old heresy now excommunication-worthy doctrine.

Into this modern era of postmodernist extremism, we find the occasional historian, often also a physician, who seeks to bridge the two approaches. In this vein, one might place such worthies as Owsei Temkin, Roy Porter, and the current author, Edward Shorter. But if they err in any direction, it seems to me, it is where the current climate is most forgiving -- towards the postmodern faith.

Shorter's work over decades has been a great benefit to psychiatry, in my view. His History of Psychiatry is, I think, the best single volume to read on that topic. In that work in particular, he received some fire from postmodernists who thought he gave too much credit to the biological in psychiatry, and was too critical of psychoanalysis. I think Shorter hit the balance just right, criticizing all sides, but also recognizing merit in biology.

In this book, Shorter turns to a more extended critique of the biological approach in psychiatry, especially as directed to the DSM-III diagnostic system, and the subsequent rise of antidepressant medications. His overall critique is sound, I think, and his historical work is solid; but his clinical beliefs are, in my view, one-sided and detract from the other merits of the book.

Shorter has gone to the American Psychiatric Association (APA) archives and dug up entertaining and informative minutes of many of the DSM-III task force proceedings in the 1970s; he also returned to interview Robert Spitzer and others involved in the process. He also read up on the FDA committee notes about the various studies on the new generation antidepressants in the 1980s and 1990s, as well as earlier FDA records in the 1960s when the new rules requiring randomized clinical trial (RCT) evidence for drug approval were instituted. His historical sleuthing is first rate.

For instance, he nicely reconstructs the whole debate about whether to include the concept of "neurotic depression" in DSM-III; how the term "minor" depression was rejected as implying that the illness was, well, minor; how the term "major" depression was created in the end to capture some of these milder kinds of depressions as well as the more severe melancholic version that had originally been intended; how the psychoanalysts rebelled at the last second to preserve their livelihoods based on insurance reimbursement for neurotic depression; and how a "neurotic peace treaty" was devised whereby dysthymia and generalized anxiety disorder were invented to allow the psychotherapists something to bill.

Shorter seems more personally explicit in this book than in the past; after documenting all the politics behind DSM-III, he concludes that there is a "complete bankruptcy of the mood disorders".

He then follows with a description of the subsequent exploitation of DSM-III by the pharmaceutical industry in marketing the SRIs. The stage was set by the FDA's new rules, which legitimized Evidence-based Medicine (EBM) methods, in the 1960s and 1970s. Using FDA meeting archives, he describes how the FDA moved from being hostile to the pharmaceutical industry in the 1960s and 70s to being compliant with it in the 1980s and 90s. He concludes that the FDA's later obsession with "the average effects" seen in RCTs produced a "regulatory nihilism" whereby all negative studies were discounted, and small positive effects were exaggerated in importance. For instance, having required two positive studies versus placebo for approval, the FDA ignored all negative studies. With prozac, for instance, 6/8 studies were negative. With Zoloft, all inpatient studies were negative; the drug was solely approved based on a few positive outpatient studies, the FDA knowing full well that it would also be used in hospitals, despite proof it did not work in those patients. Worse, such negative studies usually went unpublished, and thus clinicians did not know that they were using disproven agents in certain settings. (I will add that a recent analysis of the FDA database indeed found that published RCTs with new antidepressants produced about a 95% positive-5% negative ratio; but once unpublished RCTs available at the FDA are included, the actual ratio is 51% positive -- 49% negative).

Shorter is refreshingly catholic in his criticisms; he does not aim solely, or even mostly, at the pharmaceutical companies (everyone's favorite bugaboo these days), but also at the FDA, at the APA, and at the average psychiatrist. (I might also have added the average patient, who so often demands drugs for symptoms).

I could go on at length about the meat of this history, which is important and useful, but I will leave it to readers to see it for themselves. Despite my approbation of most of the book, I will spend more space on my critique of what I think is its major flaw, a flaw which comes across throughout the book in asides and clinical assumptions, and is reflected in its, at times, overly critical tone.

As a non-clinician, Shorter's clinical views are based to some extent on his clinical consultants, and the ones he uses represent a specific ideology in psychiatry, which though not without merit, is not, in my view, wholly supportable. These clinicians support ECT as the most effective treatment in psychiatry, and they are quite suspicious of the pharmaceutical industry (Shorter and one of this group, David Healy, have written a laudatory history of ECT). They are critical of most psychiatric diagnoses as now used, especially depression and bipolar disorder, as well of the evidence-based medicine (EBM) movement of recent years, with its emphasis on clinical, rather than biological, research. They think that such socially constructed concepts should be replaced by more biologically solid notions, like the old syndrome of "melancholia," a severe condition of depression with physical stereotyped symptoms (especially psychomotor retardation), biological correlates (marked overactivity of the adrenal gland reflected in a positive dexamethasone suppression test, DST), and perhaps most importantly, exquisite responsiveness to ECT but poor response to the Prozac prototypes.

There are scientific and historical problems with these beliefs.

Scientifically, I am not a DST expert, and perhaps I am mistaken, but my reading of this literature is that DST is not specific, being positive in non-melancholia syndromes (in most psychotic conditions, like psychotic depression and psychotic mania and schizophrenic psychosis; and even in nonpsychotic conditions with elevated psychological and physiological stress, like PTSD).

Perhaps more importantly, to privilege biological over clinical research is a Galenic move that itself has been disproven by the history of medicine; Galenic theory, based on the best biology of its time, held back medical progress (one must insist on the word) for two millennia. It led to bleeding and purging and much more harm than good, until it was disproven by….clinical research, statistics, Pierre Louis' numerical method, all of what later led to randomized clinical trials and clinical epidemiology -- the foundation of what is now called EBM. There is no doubt there is a case to be made against EBM, but there is also a strong case for it, both scientifically and historically.

It may turn out, further, that melancholia as a syndrome is not, contrary to this group's beliefs, diagnostically important. It was the view of Kraepelin (presaged by Pinel) that recurrence was the hallmark of a condition like MDI, not the specific poles of melancholia and mania. This concept has some biological support as well (e.g., circadian rhythm research), and it is completely ignored in much of the writing of this group of clinicians and historians (e.g., Healy's book on the history of bipolar disorder). If recurrence is the key aspect of this condition, then the diagnosis of MDI would be more clinically and scientifically valid than the pathological state of melancholia (or mania for that matter).

Finally, regarding ECT, the matter is much more complex than simply viewing it as the most superior treatment for almost any psychiatric condition, including melancholia and mania. ECT is only a superior treatment short-term; it has never been shown to be better than anything else long-term (and rarely with randomized data; recently, the largest RCT of maintenance ECT found it was equal to drugs, without a placebo control for us to know if either treatments were really effective at all, given that one-half relapsed in a year, the same result by the way as the largest RCTs of antidepressants). My understanding is that in earlier days (1960s-1970s), ECT specialists used ECT only acutely, and they used lithium for long-term prophylaxis (not just for depressive but also of manic episodes, in the Kraepelinian view that they were preventing recurrence, with polarity being unimportant). That is how ECT was useful: to generate acute euthymia wherein one could then institute lithium prophylaxis. (I have been told this by some of the former students of the same ECT specialists consulted in Shorter's book).

In contrast, ECT in recent years has been more widely used for ideological and economic reasons: Ideologically, doctors have become lazy about diagnosis, or believe perhaps postmodernistically that clinical diagnoses do not matter; this faith in the unimportance of clinical diagnosis is then used to justify the nonspecific use and benefit of ECT for everything (depression, mania, psychosis). Economically, managed care insurance companies do not question weeks of hospitalization for ECT, whereas they breathe down doctors' necks when patients are only receiving medications. Thus, patients get discharged without careful diagnosis, without any thought-through long-term drug prophylaxis, and end up either rehospitalized once ECT wears off, or are committed to maintenance ECT largely by default. I have no problem with the acute use of ECT, if combined with careful clinical diagnosis, and good long term drug prophylaxis, especially with mood stabilizers. This is how it is practiced by Italian mood disorder specialists, like Athanasios Koukopoulos in Rome and his group, who see themselves as inheritors of the mantle of the founder of ECT, Lucio Bini. But by demeaning drugs to mere artifacts of EBM + pharmaceutical marketing, as is the drift in this book and in others by its consultants, ECT is left as only a short-term fix which guarantees long-term relapse.

It is good to be critical about the history of our clinical diagnoses and our clinical research on its treatments; it is harmful to be cynical about both, to deny the clinical value of even our most historically and scientifically solid diagnoses. One might share much of the critique of depression and antidepressants -- though even there it can go too far in the direction of either postmodernist nihilism or biologist biases -- but it is truly a veering off in the direction of Foucaultian fantasy to deny, as some in this group do (though not Shorter so far) the clinical validity of most of the presentations of most mental illnesses, even the best established, like manic-depressive illness, and to deny the utility of even our most scientifically proven treatments, like lithium.

Shorter's book is best as history and critique, weakest as science and solution. There is much that is wrong with DSM-III and its depressive nosology, and much that is mistaken in our use of new antidepressants. The concept of neurosis needs to be reconsidered and rehabilitated; the notion of melancholic depression is important; our antidepressant treatments are less effective in many ways than claimed. This history well documents those claims. But ECT is not the cure-all, biological research is not more sound than clinical, and replacing disease nosology with psychopathology, like melancholia, will not entail our mellifluous manumission from all this mistaken misery.

S. Nassir Ghaemi, M.D., M.A., M.P.H., Director, Mood Disorders Program, Tufts Medical Center, Dept of Psychiatry. Dr. Ghaemi is author of The Concepts of Psychiatry: A Pluralistic Approach to the Mind and Mental Illness, Johns Hopkins University Press, 2003.

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