How Prozac Slew Freud


When the psychiatrist Herbert Meltzer did his post-M.D. training (his residency) in the mid-1960s, the Massachusetts Mental Health Center was at the epicenter of American psychiatry. “It was dominated by psychoanalysts,” he recalls, “who were totally committed to psychodynamic psychiatry. Even their approach to schizophrenia was psychoanalytic.”

Around that time Donald Klein, later a prominent biological psychiatrist, was working at New York’s Hillside Hospital, whose two hundred beds all were reserved for psychoanalytic therapy. Already dubious about analysis, Klein was the only doctor in the hospital allowed to write prescriptions for medication. “They’d call me and say, ‘Look, I want Mrs. Jones on Thorazine [an antipsychotic drug], two hundred milligrams,’ and I’d say, ‘Why?’ and they’d say, ‘Well, she’s schizophrenic,’ and I’d say, ‘Yeah, but she’s been here how long, ten months, and she’s been schizophrenic all along. Why do you want to give it now?’

“They’d say, ‘Well, she hasn’t responded to the therapy and we think that it’s probably a good idea.’ When you’d talk to the patient about it, the patient would say, ‘It’s okay by me, but it means the doctor has given up on me.’ When you’d talk to the ward staff about it, they’d say, ‘She kicked a maid last week, and we’re not going to put up with that.’”

Hospitalization was not only confused in its purpose; it was also exceptional. The world of psychoanalysis turned on the axis of Main Street practitioners in private offices treating middle-class patients for unhappiness. Wealthier patients might see the inside of a place like Hillside Hospital, where they would receive talking therapy. Those with grave problems were forgotten in red-brick state mental hospitals, beyond the interest of psychoanalytic psychiatry.

Then, in the 1960s and 1970s, the psychiatric world began to abandon psychoanalysis and revive the nineteenth-century tradition of psychiatry as neuroscience. Crucial events leading to this neuroscientific revival had begun much earlier, with systematic experimentation to study the chemistry of the brain. Brain chemistry means neurotransmitters, the chemicals that carry nerve impulses from one neuron, or nerve cell, to another, traveling via the synapse, the gap between the neurons. Although such research went back to turn-of-the-century English physiologists, it was only in the early 1920s that Otto Loewi, a professor of pharmacology at the University of Graz, isolated the first neurotransmitter, and not until 1926 that he was able to say that a chemical called acetylcholine mediated the transmission of nerve impulses from one nerve to the next.

The discovery of acetylcholine did not remain abstract knowledge but had rapid therapeutic consequences; in the 1930s psychiatrists out of pure desperation began administering doses of it to their patients in hopes of relieving schizophrenia—even though they had no notion of how its mechanism worked. The results were indifferent, but many doctors remained optimistic, and in 1952 their confidence was justified with the discovery of a powerful new anti-psychotic drug called chlorpromazine, an antihistamine not related to acetylcholine. That same year a group of Paris physicians, including the anesthetist Henri Laborit and the psychiatrists Jean Delay and Pierre Deniker, learned that agitated psychotic patients, locked in the grips of their voices and delusions, became vastly better once they began taking the new drug. It had been developed by a French drug house and was marketed in the United States as Thorazine once the American pharmaceutical firm Smith Kline & French (as it then was) had bought the rights.

The impact of chlorpromazine on psychotic patients was sensational. At the time, Donald Klein was in charge of a ward for World War I veterans at a Public Health Service hospital in Lexington, Kentucky, where, he says, “these people had been psychotic for thirty years. They were out of it completely.” After he began giving chlorpromazine, he recalls, “a guy who hadn’t said anything for thirty years comes over to me after a few weeks and said, ‘Doc, when am I getting out of here?’ It was Rip Van Winkle. He had remembered nothing. The last thing he remembered was in 1916 going over the trenches. That was an honest-to-God miracle.”

The miracle drug had major disadvantages. It tended to produce involuntary movements, in their chronic form called tardive dyskinesia, which many patients found embarrassing, often causing them to stop taking the drug after they were discharged from the institution; nobody knew how it worked (on the other hand, nobody knew how aspirin worked either); and there were reservations about treating what were seen as the symptoms of mental distress rather than its causes. Yet chlorpromazine’s obvious effectiveness gave it the same persuasive punch as penicillin.