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.