How Prozac Slew Freud

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Consulting for a drug house named Carter Products, whose chief previous claim to fame had been Carter’s Little Liver Pills, Berger, a gifted scientist and medical thinker, produced a drug, later given the generic name meprobamate, that reduced quotidian anxiety. Carter lost interest in the product after asking a sample of physicians if they wanted such a thing.

 

Eventually it made its way to the market under the name Miltown and generated a greater demand than any drug previously marketed in the United States. In 1960 Hoffmann-La Roche, a Swiss pharmaceutical firm with a large American arm, brought out Librium (chlordiazepoxide), the first of the antianxiety drugs called benzodiazepines. Valium (diazepam) followed three years later, in 1963.

These drugs began to change the pattern of psychiatry. For the first time, psychiatrists had something to offer their patients other than hour after hour of talk therapy, something that would make an immediate difference in how they felt without sedating them the way barbiturates had done. By 1975 a quarter of all office visits to a psychiatrist were ending with a prescription. There was, however, one problem: The benzodiazepines turned out to be addictive. In 1975 the Food and Drug Administration put Valium and the other “benzos” on its list of controlled substances.

As antianxiety drugs appeared, so did ones that fought depression. In 1950 the Swiss firm Geigy (since folded into Novartis) launched Tofranil (imipramine), the first really effective medication for depression. Scads of others followed, a so-called first wave of antidepressants. The second wave came in the early 1980s. In consultation with the Swedish neuroscientist Arvid Carlsson, the Stockholm pharmaceutical company Astra came out with a new drug that affected the chemical neurotransmitter serotonin. After a neurotransmitter has carried a nerve impulse across the synapse from one nerve cell to another, the neurotransmitter is taken back into the nerve cell that discharged it. This is called reuptake. The new drug helped serotonin to remain longer in the synapse, by selectively inhibiting its reuptake. By some mechanism not fully understood, this tends to reduce depression. Drugs using the process soon became identified by the acronym SSRI: selective serotonin reuptake inhibitor.

Astra’s new drug, Zelmid (zimelidine), was highly effective, but it turned out to cause unacceptable side effects and was withdrawn from the market before it ever reached the United States. Nonetheless, Carlsson and Astra’s work was quickly built upon. In Indianapolis, Indiana, the Eli Lilly Company had been working independently on its own SSRI and came up with a compound that, although no more effective than the first-generation antidepressants, acted more quickly, had fewer side effects, and even produced weight loss. Lilly introduced the new drug in December 1987 as Prozac (fluoxetine). It went on to become the most successful psychiatric drug in history.

What with the success of the new SSRIs in treating depression, depression itself began to change. Once it had been an unusual condition that often led to hospitalization or even suicide; by the early 1990s the definition of depression had been greatly expanded to include a range of disorders that responded to new drugs like Prozac, and it was transformed into a common malady for which help was readily available. Today almost half of all visits to American psychiatrists are for mood disorders, depression chief among them. Moreover, the SSRIs are so straightforward to administer that many physicians other than psychiatrists prescribe them; one-third of antidepressants, for instance, are prescribed by family doctors.

The discovery of the antidepressants, the antipsychotics, and the other highly effective psychiatry drugs represents an epochal scientific accomplishment. For example, lithium, for mania and chronic depression, is one of the most effective medications in psychiatry. But if, as the British psychiatrist David Healy puts it, “drugs created biological psychiatry,” then the researches those drugs fostered have now come full circle, with the news that psychotherapy too can affect brain chemistry. In a series of studies in the early 1990s, a team at the UCLA School of Medicine demonstrated that if you treat obsessive-compulsive disorder with psychotherapy, the elements of brain chemistry suggestive of psychiatric illness may disappear. So psychotherapy can be effective. Still, psychoanalysis as a form of psychotherapy is no more effective than any of 130 other kinds of psychotherapy, and it’s a great deal slower and more expensive.

Psychotherapy has always existed in medicine, the doctor acting upon the patient’s mind in the context of a one-on-one relationship. Few examples of its efficacy are more dramatic (or extreme) than one related by the English psychiatrist Sir James Crichton-Browne, about R.W., a patient of his who had been admitted following a head wound suffered in the First World War. R.W. had “never quite recovered from the accident, was afterwards dismissed from the Service, and ultimately found his way into the asylum in a state of maniacal excitement.” He was “restless and sleepless and miserable, and became greatly emaciated and haggard.”