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Before Prozac: The Troubled History of Mood Disorders in Psychiatry

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Shorter's critique is complicated and multifactorial (and he frequently gets distracted by historical curiosities), but lives may depend on it. The main thrust of his argument is that Psychiatry has not progressed as other medical specialties have, because the classification of illnesses and the medications used to treat them are inferior to the state of the art 40 years ago. This came about because 1. Major Depression was so broadly defined as to be a meaningless diagnosis, 2. The FDA decreed that drugs had to be indicated specifically for a particular use (antidepressant, antipsychotic, anxiolytic) 3. The early FDA arbitrarily wiped out or vilified whole classes of drugs as an exercise of power, and 4. the later FDA adopted a standard for efficacy of double-blind trials against placebo, without regard for relative effectiveness of other drugs.

The political document known as the DSM is certainly an easy target. Shorter's main objection is the classification of depressive disorders. He believes that clinically useful categories would be melacholic depression (what used to be called clinical depression, meaning slowed physical reactions, inability to get out of bed, high cortisol levels, sleep disturbance, anorexia, feelings of guilt) with the first line of treatment being tricyclic antidepressants; Atypical depression (increased sleep and appetite) with the first line of treatment being MAO inhibitors; and Neurotic Depression, covering a wide swath of the worried well (who now, along with the other two, now meet the diagnostic criteria for "Major Depressive Disorder"). For these, he marshals evidence that SSRI's can be effective, but not as much as meprobromate, librium, valium, chlorpromazine, and even ritalin, amphetamine and barbiturates. Shorter argues that the distinction between an antidepressant and an anxiolytic is not important in neurotic depression. (It is interesting that Abilify is now being promoted as an adjunctive treatment of depression; one wonders whether a cheaper phenothiazine would work as well.) The problem is not so much what psychotropic is in fashion for the "neurotic" depressives, but that people with the old depressive symptoms (affective disorders used to be considered psychoses) are being treated with drugs that barely beat out placebos, and never come close to the effectiveness of the antidepressant drugs used in the 1960's. Since suicide is a complication of melancholic depression, this is a serious issue.

His history of the FDA is illuminating. Like the changes in the DSM, the policy at the FDA was based on politics, not science. In the early days, many drugs were banned or restricted; some of them were probably useful. Just about all of the belladonna compounds were tossed out; some of these had been used as antidepressants, notably benactyzine. Was there promise in developing or modifying this antimuscarinic drug? We will never know. Shorter points out that many psychotropic drugs including the phenothiazines, the tricyclics, and early SSRIs, are antihistimines. He notes that chlorpheneramine is an effective anxiolytic and serotonin reuptake inhibitor (available over the counter at your local Walgreens for $5 per silo). As a personal aside, I will never forgive the FDA for banning belladonna alkaloids from cold remedies. Now instead of scopalamine, which will actually dry your mucus when you have a cold, there is only antihistimine, which is great for allergies but useless for colds. Belladonna alkaloids are effective as antiemetics and soporifics as well.

At times Shorter overstates his case. He minimizes the danger of barbiturates, which are every bit as lethal, addictive and dangerous as the FDA claimed. He plays down the (obvious) addictive potential of the benzodiazapenes, although he makes a good case that the FDA and others have overestimated it. He minimizes the side effects of tricyclic and MAOI antidepressants, even claiming that they are equivalent to the side effect profiles for SSRI's, but he admits in one place that the side-effects of the tricyclics were so obnoxious that people stopped taking them as soon as possible.

Shorter's other excellent books on psychiatric history focus mostly on neurotic disorders. This is his interest, so the book is mostly focused on depressive disorders. He could have made similar points regarding antipsychotic medication. Studies have shown that cheap, out of patent phenothiazines and haloperidol are just as effective as the superexpensive new designer drugs, and when dosed carefully, have no more side-effects. Zyprexa is highly effective, maybe the most effective of the newer antipsychotics, but I have seen people gain 20 pounds a month while taking it. It's bad enough that people with schizophrenia smoke so much, do we have to turn them into Type II diabetics, too?

Whatever we think of the new drug set, there is nothing new in the pipeline for affective or psychotic disorders. Shorter is exasperated with the lack of progress in Psychiatry. When the drug companies were throwing lots of money at research (although not as much as they claim--much of it was paid for by government grants) they came up with a set of new drugs for depression and anxiety that are not as effective as the old set. He offers no hope for the future of psychiatric treatment beyond reconsidering the older drugs.

Prof. Shorter provides a fascinating exploration of the psychopharmacology of mood disorders and psychiatry in the 20th century. He describe the early discovery of medications useful in the treatment of the different forms of depression and anxiety (and the general angst of modern life). Some of the most effective treatments were found amongst these early medicines. He describes the ascendancy of the FDA in the 60's and how its flexing of muscles led to the disappearance of some of them based on politics instead of science. Later, the FDA would adopt the policy of approving medications based solely on their ability to outperform placebo. Shorter argues that this has led to weakly effective drugs for mood disorders; he primarily claims that they should be compared to older treatments to see if they are an improvement over the old. (Ideally, a comparison of the new to both placebo and old would be best.)

Prof. Shorter also describes the evolution of the diagnosis of depression with changes in the DSM. He relates how the diagnosis of major depression was more a political consensus to partially placate the psychoanalytic community and less about what was understood about the biological roots of depression. He claims that this new categorization of major depression included the "neurotic" and "melancholic". Making a distinction has implications in treatment.

Prof. Shorter concentrates on the more familiar mood disorder, depression; he does not cover bipolar disorder or schizophrenia. For a history of depression and modern psychiatry, this book is very useful.

Whether this is a reliable history of 20th-century psychopharmacology I don't know. The writing, however, is insufferably dull. Seems to me like little more than a parade of dates and events. This is, incidentally, not a history of psychiatry (say, of the varied diagnosis and treatment of mood disorders). It's a history of psychopharmacology.

Prof. Shorter, a well known historian of psychiatry, cites chapter and verse on why the SSRI antidepressants are only marginally effective and probably should not have been approved by the FDA. He quotes damning minutes of internal FDA deliberations about the SSRI's (including astonishing statements by Paul Leber, then-FDA director of new drug approval) confirming Peter Breggin's claims about the ineffectiveness and dangers of SSRI's, the FDA's misleading drug approval process and the pervasive influence of drug industry money on all of it. Prof. Shorter cites scientific, financial and cultural influences he believes make modern psychiatry actually less able to help depressed people than in the 1950's.

This book illustrates bio-psychiatry's history of downplaying its shortcomings until it is convenient to acknowledge them. (Other examples include E. Fuller Torrey's criticism of accepted biological theories in order to advance his own biological take on schizophrenia; drug companies market their products as "safe and effective" until the patents expire, and then reveal the old drugs' problems, touting their "new and improved" drugs that allegedly correct the previously minimized problems).

Prof. Shorter lambasts present day psychiatry, contrasting it with the 1950's and `60's as the hayday of psychiatry. His critique of current practice is persuasive, but his case for psychiatry's good old days is not: he claims amphetamines, MAOI's, benzodiazepines and first generation anti-psychotics were far more effective than most current drugs - but Irving Kirsch's The Emperor's New Drugs, for example, cites meta-analyses showing the old antidepressants' effectiveness virtually identical to today's SSRI's.

Similarly, Prof. Shorter criticizes psychiatry's past and present prescribing fads, stating that psychiatry knows so little about the physical aspects of mental problems that psychiatrists have scant reliable basis to evaluate PhARMA's claims about "hot" new drugs. In light of psychiatry's confident public posture as "experts" and ultimate authorities, these are stunning admissions - another case of psychiatry's acknowledging inconvenient truths only when it serves to refute someone else's position. Prof. Shorter doesn't follow his own reasoning to its logical conclusion - if he admits psychiatrists don't really know very much, why should we defer to their allegedly scientific model?

But Shorter does not fully appreciate that, whatever psychiatry's current state of ignorance, it is less ignorant now than what existed in his `50's golden age; so why would the impressionistic "clinical judgment" of the '50's be better than what we have now? While criticizing today's placebo-controlled clinical trials as manipulated by PhARMA, he doesn't notice that the `50's less structured communication of clinical impressions among psychiatrists - of which he approves - seems even less reliable, with disastrous results. In the `50's, before placebo controlled clinical trials, lobotomy was for years an accepted treatment for schizophrenia - it's inventor won the 1948 Nobel Prize for medicine and lobotomy persisted well into the '50's. Back then, it took psychiatry 20 years to admit Thorazine causes tardive dyskinesia, and millions of housewives were hooked on benzodiazapines.

Shorter's indictment of modern psychiatry can't be dismissed as the work of a marginal "anti-psychiatrist." He chairs a department at a major university; he has published scholarly books on the history of psychiatry. He clearly loves and respects the field of psychiatry. But he loses objectivity when he longs for "the good old days."

This was a very well researched book (with many citations) which presented a very convincing argument. I really enjoyed it. I would sum up the main argument of the book as saying the drugs we have today for treating mental illness (especially depression) are worse than the ones we had in the past largely because of the power-wrangling of the FDA, and the compromise-based nature of the DSM. Shorter argues that MDD (major depressive disorder) isn't a real illness, in that it is a heterogenous category that doesn't "cut nature at the joints."

(Also, as a libertarian, it was nice to read something that gave the FDA and the drafters of the DSM the blame they deserve. The pharma industry isn't innocent, but it was nice to encounter something that didn't blame all of the problems in mental health treatment on its capitalist excesses. I don't mean to suggest that people of other political persuasions won't enjoy and benefit from this book, just that libertarians should take special note of it.)