Shrinks (24 page)

Unfortunately, there’s quite a bit of difference between natural deep sleep and the sleep produced by a chemical strong enough to knock out an elephant. Deep sleep therapy can elicit a cauldron of scary side effects, including coma, cardiovascular collapse, and respiratory arrest; one of Macleod’s own patients died during his experiments. It was also difficult to judge the right dose, and sometimes patients slept for a day or two longer than intended. Most problematic was the fact that bromide is a toxin that builds up in the liver, becoming more harmful with each use.

At first, bromide compounds spread rapidly through public asylums because they were cheaper and easier to manufacture than chloral, while producing more potent effects. The “bromide sleep cure” was briefly taken up by other physicians, too, before being abandoned as too dangerous.

Even though morphine, chloral, and bromide were all crude and addictive sedatives with harmful side effects, the notion that drug-induced sleep was therapeutic became firmly established by the start of World War II. (Except, of course, among the psychoanalysts, who dismissed sleeping pills out of hand, insisting they did nothing to resolve the unconscious conflicts that were the true mainspring of all mental illness.) Even so, no psychiatrist, psychoanalyst or otherwise, believed that there would ever be a drug that targeted the symptoms of mental illness or empowered a patient to lead a normal life—at least, not until 1950, the year the first
psychopharmaceutical
drug was born, a drug providing true therapeutic benefits for a troubled mind.

Despite the drug’s momentous impact, I’d wager you’ve probably never heard of it:
meprobamate
. Originally marketed as Miltown, this synthetic medication alleviated anxiety and elicited a feeling of calm without putting patients to sleep. In the first peer-reviewed article describing meprobamate, the author characterized its effects as “tranquilizing,” giving rise to the name of the first class of psychopharmaceuticals:
tranquilizers
.

Psychoanalysts denigrated meprobamate as just another chemical distraction that concealed mental illness rather than treating it, but the Freudians were the only ones to pooh-pooh it: meprobamate wasn’t merely the world’s first psychopharmaceutical, it was the world’s first psychotropic blockbuster. By 1956, an astonishing 36 million prescriptions for the tranquilizer had been written; one out of every three prescriptions in the United States was for meprobamate. It was prescribed for everything from psychosis to addiction and came to be associated with overwrought housewives—giving rise to its popular sobriquet, “Mother’s Little Helper,” immortalized by the Rolling Stones.

Meprobamate was superseded in the 1960s by the introduction of Librium and Valium, a new generation of internationally popular tranquilizers. (The bestselling contemporary benzodiazepines are Xanax, for anxiety, and Ambien, for sleep.) All of these drugs trace their origins to Macleod’s deep sleep therapy at the dawn of the twentieth century.

While meprobamate was unquestionably effective in reducing the symptoms of mild anxiety disorders, it was not a pharmaceutical game-changer like antibiotics for bacterial infections, insulin for diabetes, or vaccines for infectious diseases. It had no effect on the disturbing hallucinations, painful melancholy, or frenzied mania of patients locked away in public asylums, so it offered no hope for recovery for those unfortunate souls suffering from severe mental illness. Even after meprobamate become a psychiatric smash hit, the prospect of finding a simple pill that could ameliorate psychosis seemed as fanciful as schizophrenics’ delusions and as remote as the asylums that imprisoned them.

Laborit’s Drug

In 1949 a French surgeon named Henri Laborit was seeking a way to reduce surgical shock—the low blood pressure and rapid heart rate that often occurs after major surgery. According to one of the prevailing hypotheses at the time, surgical shock was due to the excessive reaction of a patient’s autonomic nervous system to stress. (The autonomic nervous system is the unconscious circuitry that controls our breathing, heart rate, blood pressure, and other vital functions of the body.) Laborit believed that if he could find a compound that suppressed the autonomic nervous system, it would increase the safety of surgical procedures.

Working in a French military hospital in Tunisia—not exactly the epicenter of the medical world—Laborit experimented with a group of compounds called antihistamines. Today these drugs are commonly used to treat allergies and cold symptoms, but at the time scientists had just learned that antihistamines affect the autonomic system. Laborit noticed that when he gave a strong dose of one particular antihistamine, known as
chlorpromazine
, to his patients before surgery, their attitudes changed markedly: They became indifferent toward their imminent operation, an apathy that continued after the surgery was completed. Laborit wrote about this discovery, “I asked an army psychiatrist to watch me operate on some of my tense, anxious Mediterranean-type patients. Afterwards, he agreed with me that the patients were remarkably calm and relaxed.”

Impressed by the notable psychological effects of the drug, Laborit wondered if chlorpromazine might be used to manage psychiatric disturbances. Pursuing his hunch, in 1951 Laborit administered a dose of chlorpromazine intravenously to a healthy psychiatrist at a French mental hospital who volunteered to serve as a human guinea pig in order to provide feedback about the drug’s mental effects. At first the psychiatrist reported “no effects worthy of mention, save a certain sensation of indifference.” But then, as he got up to go to the toilet, he fainted—the result of a drop in blood pressure, a side effect. After that, the director of the hospital’s psychiatric service banned further experimentation with chlorpromazine.

Undeterred, Laborit attempted to persuade a group of psychiatrists at another hospital to test the drug on their psychotic patients. They were not particularly enthusiastic about his proposal, since the prevailing belief was that the disruptive symptoms of schizophrenia could only be reduced by strong sedatives, and chlorpromazine was not a sedative. But Laborit persevered and finally convinced a skeptical psychiatrist to try his drug on a schizophrenic patient.

On January 19, 1952, chlorpromazine was administered to Jacques L., a highly agitated twenty-four-year-old psychotic prone to violence. Following the drug’s intravenous administration, Jacques rapidly settled down and became calm. After three steady weeks on chlorpromazine, Jacques carried out all his normal activities. He even played an entire game of bridge. He responded so well, in fact, that his flabbergasted physicians discharged him from the hospital. It was nothing short of miraculous: A drug had seemingly wiped away the psychotic symptoms of an unmanageable patient and enabled him to leave the hospital and return to the community.

What distinguished the effects of chlorpromazine so dramatically from sedatives and tranquilizers was its ability to decrease the intensity of psychotic symptoms—the hallucinations, delusions, and disorganized thinking—in the same way that aspirin reduces the pain of a headache or the temperature of a fever. A friend of mine who suffers from schizophrenia, the legal scholar Elyn Saks, writes in her memoir,
The Center Cannot Hold: My Journey Through Madness
, that antipsychotic drugs act more like a dimmer knob than an on/off switch. When her symptoms are at their worst, they cause her to hear sharp voices hurling painful insults at her or shouting orders she must obey; the meds gradually reduce her symptoms to a point where she still hears voices, but they are distant, faint, receding into the background and no longer distressing or compelling.

Chlorpromazine’s use as an antipsychotic—the
first
antipsychotic—swept through the mental hospitals of Europe with the force of a tidal wave. In the psychoanalysis-obsessed United States, in contrast, reaction to the miracle med was muted. The Smith, Kline and French pharmaceutical company (a forerunner to GlaxoSmithKline) licensed chlorpromazine for distribution in the U.S., where it was endowed with the American trade name Thorazine (in Europe it was called Largactil), and launched a major marketing campaign to convince medical schools and psychiatry departments to test it on their patients. But American shrinks derided Laborit’s drug as “psychiatric aspirin,” waving it off as just another sedative, like chloral or the barbiturates—a distracting siren song that led gullible psychiatrists away from their true task of digging for neurotic seeds buried in the soil of the unconscious.

At first, Smith, Kline and French was baffled and frustrated by chlorpromazine’s stony reception. They had in their possession a wonder drug proven to treat the symptoms of psychosis for the first time in human history, yet they couldn’t convince anybody in America of its value. They finally stumbled upon a winning strategy: Rather than targeting psychiatrists with promises of a marvelous cure, they targeted state governments using a surprisingly modern argument. Referring to “health economics” and “cost-cutting,” Smith, Kline and French argued that if state-funded mental institutions used chlorpromazine, they would be able to discharge patients instead of warehousing them forever. A few of these institutions—more concerned with the bottom line than with philosophical debates about the ultimate nature of mental illness—tried out Thorazine on their permanent patients. The results were breathtaking, just as French psychiatrists had previously demonstrated and Smith, Kline and French had promised. All but the most hopeless cases improved, and many long-institutionalized patients were sent home. After that, chlorpromazine took American psychiatry by storm. Every asylum and psychiatric hospital began to use Laborit’s drug as the first line of treatment for psychotic patients in their care. Over the next fifteen years, Smith, Kline and French’s revenues doubled three times. By 1964, more than ten thousand peer-reviewed articles had been published on chlorpromazine, and more than fifty million people around the world had taken the drug.

It is hard to overstate the epochal nature of Laborit’s discovery. Like a bolt from the blue, here was a medication that could relieve the madness that disabled tens of millions of men and women—souls who had so very often been relegated to permanent institutionalization. Now they could return home and, incredibly, begin to live stable and even purposeful lives. They had a chance to work, to love, and—possibly—to have a family.

Just as the antibiotic streptomycin emptied sanitariums of tuberculosis patients and the polio vaccine rendered the iron lung obsolete, the widespread adoption of chlorpromazine marked the beginning of the end for the asylums. It also marked the end of the alienists. It is no coincidence that the asylum population began to decline from its peak in the United States in the same year Thorazine was released.

A century and a half after Philippe Pinel freed the inmates of the Parisian Hospice de la Salpêtrière from their physical chains, another French physician released patients from their mental confinement. Psychiatry, after a seemingly interminable struggle, could finally answer the question, “How can we treat severe mental illness?”

Compound G 22355

Envious of the mega-profits generated by chlorpromazine, other pharmaceutical companies searched for their own proprietary antipsychotic throughout the 1950s. They often teamed up with psychiatrists to aid in this search, and the Swiss pharmaceutical company Geigy, a corporate ancestor of Novartis, approached Roland Kuhn, the head doctor at a psychiatric hospital in the Swiss town of Münsterlingen, on the banks of Lake Constance. Kuhn, thirty-eight, was a tall and cultivated psychiatrist who combined an exceptional grasp of the humanities with a background in biochemistry. Geigy offered to provide Kuhn with experimental compounds if he would test them on his patients. Kuhn readily agreed.

In late 1955, Geigy’s head of pharmacology met Kuhn at a hotel in Zurich where he showed him a chart scribbled with the hand-drawn chemical structures of forty different compounds available for testing. “Pick one,” the pharmacologist instructed. Kuhn carefully surveyed the forest of molecules, then pointed to the one that most closely resembled chlorpromazine, a molecule labeled “Compound G 22355.”

Kuhn dosed a few dozen psychotic patients with G 22355, but the drug failed to produce the same dramatic reduction of symptoms as chlorpromazine. Of course, as any pharmacological researcher knows, failure is the usual fate for any experimental compound—most commercial drugs are only discovered after tens of thousands or even hundreds of thousands of chemical candidates are tested and rejected. The most sensible next step would have been for Kuhn to point to a new compound on Geigy’s chart and try again. Instead, Kuhn made a very peculiar decision, one that would affect millions of lives.

The first antipsychotic was not discovered because of any orderly research plan contrived by Big Pharma; it was discovered purely by accident after a solitary physician followed his intuition about an experimental drug for surgical shock. And now a lone psychiatrist decided to ignore the task that he had been assigned—finding a chlorpromazine knockoff—and instead pursued his own private hunch about a disorder he cared about more than schizophrenia: depression.

Even in the earliest days of psychiatry, schizophrenia and depression were almost always considered distinct conditions; madness and melancholia. After all, the worst symptoms of psychosis were cognitive, while the worst symptoms of depression were emotional. When Geigy engaged Kuhn, there was no reason to believe that a class of drugs that dampened the hallucinations of psychotic patients would also elevate the mood of depressed patients. But Kuhn held his own staunch ideas about the nature of depression.