Before Prozac: The Troubled History of Mood Disorders in Psychiatry
Edward Shorter
Oxford University Press. 304 pp. ISBN: 9780195368741

It’s now been more than 30 years since the advent of SSRIs like Prozac and its descendants (Zoloft, Luvox, Celexa, Paxil, Lexapro, etc.) triggered what many consider a psychopharmaceutical revolution in psychiatry.
As these medications gained popularity, psychiatry lost its final connections to talk therapy and abandoned the use of an older generation of “ineffective” mood medications. There’s only one problem with this widely accepted success story, according to historian Edward Shorter in his new book, Before Prozac: “Most of the antidepressants today don’t work very well. That is, in contrast to the 1950s and ’60s, when some truly effective medications for mood disorders were available.”

Shorter’s book is a rip-roaring assault on the practice of modern psychiatry that makes some large claims, the ineffectiveness of the SSRIs not even being the largest. Over the past two decades, he argues, psychiatry actually has gone backward. “Medicine is supposed to make progress, to go forward in scientific terms,” he writes, “so that each successive generation knows more and does better than previous generations. But this hasn’t occurred by and large in psychiatry, at least not in the diagnosis and treatment of depression and anxiety.”

It’s Shorter’s contention that a host of suitable drugs were developed for depression and anxiety in the 1940s and ’50s: the tricyclic antidepressants (the TCAs), like amitriptyline and imipramine. But even effective drugs eventually lose their patents, resulting in the proliferation of generics and an inevitable decline in profits, which is hard on the bottom line of drug companies. Fortunately—at least this is the drug companies’ viewpoint—the SSRIs came along to save the day. They were, and still are, touted to be more effective and to have fewer negative side effects—or at least more tolerable ones—than previous drugs. The pharmaceutical companies made billions selling them, abandoning the older drugs that generic firms could manufacture at a fraction of their initial cost. The companies focused on sending reps to shrinks’ offices to talk up the benefits of their new products to every doc they could meet, and distributed free samples like candy.

Shorter is certainly not the first critic to draw this picture of the pharmaceutical industry, but he carries it farther. He disputes the idea that patients tolerate the SSRIs better than TCAs and offers quotes from psychiatrists and other citations to back up his claim. He contends that “there has never been a more effective antidepressant drug than imipramine,” even though it was first launched in the American market in 1959. He believes that the adverse side effects of SSRIs have been vastly underreported, and that they are much more intrusive than those caused by the older TCAs. “Dear Reader,” he writes drolly, “which would you rather have: impotence or [TCA] dry mouth?” Psychiatrists and patients may dispute Shorter’s claims of the effectiveness of TCAs, but that doesn’t stop his sometimes offhand polemics, buttressed by piles of footnotes.

A second culprit in the foisting of more expensive and less effective psychotropic drugs on the public, in Shorter’s view, has been the Food and Drug Administration (FDA). He says the FDA was a more or less one-horse operation, when, beginning in the 1950s and especially in the 1960s, it vastly expanded its turf and began to play “tough new kid” on the block. It also began to establish boards to review older medications and generally show drug companies who was boss. As a way to bolster its image and begin doing what Shorter calls, “empire building,” it took on supposedly unsafe, sedative drugs, like meprobamate, marketed as Miltown and Equanil, even though, according to Shorter, Miltown was “one of the most effective agents in the history of psychiatry.”

At that time, the staggering sales and unprecedented popularity of tranquilizers had triggered a politically motivated panic that the population was in danger of falling into the grip of “addictive” drugs (another example of the “moral panics” that one historian quoted by Shorter claims periodically sweep through America). Shorter contends the FDA used these fears to expand its regulatory power. For him, public bureaucracies are like profit-making companies: they have a built-in need to grow and expand.

After antianxiety meds like Valium and the earlier sedative Miltown were roundly discredited by bad publicity, congressional hearings, and a muscle-flexing FDA, the drug companies began to shift their attention to the treatment of depression with meds that were unsullied by suspicions about their addictive potential. Starting in the 1980s and ’90s, they put more resources into promoting antidepressants. Many of these meds had been patented much earlier in Europe, and then were rebranded and introduced into the U.S.

In an attempt to strengthen the scientific basis of regulation, the FDA began at this point to insist on the “gold standard of psychiatric evidence, the randomly controlled trial.” Before that, drugs came to market after small, more open trials, in an assortment of ways (which means perhaps without control groups and without insuring that patients and prescribing doctors didn’t know whether experimental drugs or placebos were being used in a given case). Shorter doesn’t explicitly state how, but it seems the whole drug-certification process was a lot more casual in the 1960s and ’70s. Ultimately it was the determination by doctors of how drugs performed clinically that influenced the approval of new meds.

While the randomly controlled trial is more scientifically scrupulous, of course, there’s a downside: under the new regime, drug firms weren’t required to test their new meds for effectiveness against other, existing medications, many now fading from public favor and losing patent protection. They only needed to measure up against a placebo. Bottom line, says Shorter: “If you can beat sugar pills, you can get your drug licensed.” Still, even with this low bar, in preliminary drug company trials, Prozac proved little more effective than the placebo.

For Shorter, the third culprit in all this is the psychiatry profession itself, as it presents itself in its Diagnostic and Statistical Manual (DSM). The first edition of the DSM was published in 1952 and then revised in 1968 and 1980. (We now live with the DSM-IV, and the next version will be out in 2012.) The purpose of these manuals is to standardize psychiatric diagnoses. But in Shorter’s judgment, rather than being a product of the most rigorous scientific conclusions about psychiatric conditions, the DSMs are actually consensus documents, which often say more about the politics of psychiatry than anything about the latest empirical findings.

For Shorter, the turning point in the understanding and treatment of depression, and the reason that the diagnosis became so common, happened with the development of the DSM-III. In the 1970s, under the aegis of Robert Spitzer, a Columbia professor, a task force was set up to revise DSM-II. Shorter chronicles in great detil the politicking and in-fighting that went into DSM-III, particularly the psychoanalysts’ protests about the elimination of their familiar diagnostic labels.

The upshot of these political battles and compromises was that the new DSM became a kind of “Chinese menu” of psychiatric disorders, with no unifying theoretical or scientific coherence. For example, a range of what many considered separate conditions were put into one big basket called “major depression” (Spitzer’s term), graded on a scale of severity from one to three. Dysthymia, a milder, chronic disorder, was given its own category. But according to Shorter, the compromise formulation for depression hopelessly distorted the diagnosis, transforming it into a one-size-fits-all category.

Shorter believes that, in the process of updating DSM-II, crucial distinctions about different types of depression were lost, handicapping the future development of effective, more focused treatments. What used to be called “melancholic depression” or “endogenous depression,” the sort of extreme state that can keep people from getting out of bed for weeks or months, was lumped together with other, entirely different depressions—which confused everyone. The result was that one, overgeneralized condition became the target for a range of drugs, many of which were best suited for “heterogeneous” depressions including “mixed states” of depression and anxiety, circumstantial depressions, and other stresses.

Today, patients can go to a doctor complaining of a variety of quite different symptoms, and still be treated under the “major depression” rubric. Much of modern-day psychiatry—
in the absence of accurate instruments for determining which meds work for which patients—is a matter of trial and error. The doctor prescribes an SSRI and, if that doesn’t work (it can take four to six weeks or more to determine if the patient is responding), the physician prescribes another, and then another. It can take a year to figure out the right medication for a patient, if, in fact, one is found.

While Shorter is extremely critical of modern psychiatry, he’s by no means antidrug. He just feels that today’s psychiatric patients aren’t getting the drugs they should be getting. But he has remarkably little to say about how to change this. He insists that no promising new drugs are in the pipeline, and suggests the best we can do is to revisit the old psychiatric medicine cabinet and rediscover pills that worked (and were tarnished) more than half a century ago.

Shorter almost entirely ignores the new brain science and the possibility of a new generation of targeted medications with a different kind of neurochemical action than has been employed so far. These are the meds that resemble smart bombs in comparison with the crude psychopharmacological sledgehammers of today, and are described by psychiatrist Peter Kramer in his book Against Depression. Certainly this is an avenue drug companies in search of greater profits are exploring as quickly as they can. With so many exciting developments in the new neuroscience, Shorter’s failure to consider their possible impact is a major flaw in his view of what lies ahead for psychiatry.

While Shorter hardly touches on talk therapy, his argument about the limits of psychiatry, even if overstated, offers reassurance to those who believe that the ultimate answers to mental health issues require something more than the right prescription. It’s hard to read his chronicle of the dead-end of modern psychiatric practice without concluding that there are too many complexities in the human experience for even the smartest drugs to smooth over. Even though it isn’t his intention, Shorter provides plenty of reason for managed care and insurance companies to reconsider the role of psychotherapy as part of the more enlightened and more effective psychiatric practice of the future.

Richard Handler

Richard Handler is a radio producer with the Canadian Broadcasting Corporation in Toronto, Canada.