6

MODERN-DAY ALCHEMY

The drug produced an effect similar to frontal lobotomy.

—N. William Winkelman Jr. (1954)¹

 

 

 

 

THE MODERN ERA of medical treatments for schizophrenia is always traced back to a specific date: May 1954. That month, Smith, Kline & French introduced chlorpromazine into the U.S. market, selling it as Thorazine. This drug was the first “antipsychotic” medication to be developed, and it is typically remembered today as dramatically different in kind from lobotomy and the other brain-disabling therapies that preceded it. In his 1997 book A History of Psychiatry, Edward Shorter neatly summed up this belief: “Chlorpromazine initiated a revolution in psychiatry, comparable to the introduction of penicillin in general medicine.” With this drug, Shorter added, schizophrenia patients “could lead relatively normal lives and not be confined to institutions.”²

But that was not at all how chlorpromazine was viewed in 1954. It was seen at that time as a pill that hindered brain function, much in the same manner that lobotomy did. It took a decade of modern-day alchemy to turn it into the “antipsychotic” medication we recall today.

First Impressions

Although eugenics had become a thoroughly shamed science by the 1950s, intimately associated with the horrors of Nazism, the therapeutics it had spawned didn’t suddenly disappear. Approximately 10,000 mental patients in the United States were lobotomized in 1950 and 1951, which was nearly as many as had been operated on during all of the 1940s. Electroshock remained a mainstay treatment in state hospitals, and it was often used to deliberately reduce patients to confused states. In 1951, for instance, psychiatrists at Worcester State Hospital in Massachusetts reported that they had successfully used repetitive electroshock to “regress” fifty-two schizophrenics to the point where they were incontinent, unable to feed or dress themselves, and mute. D. Ewen Cameron, who was named president of the American Psychiatric Association in 1952, also utilized electroshock in this way, shocking his patients up to twelve times daily, which, he wrote, produced a disruption in memory “so massive and pervasive that it cannot well be described.” Patients so treated, he said, were unable even to “conceptualize” where they were. Nor did eugenic sterilizations cease. Approximately 4,000 mentally ill patients were sterilized in the 1950s, which was about the same number as in the 1920s, when eugenic attitudes toward the mentally ill were reaching a feverish pitch. This was the therapeutic milieu that was still in place—the value system, as it were—when chlorpromazine made its debut in the state mental hospitals.³

Chlorpromazine, which was synthesized in 1950 by Rhône-Poulenc, a French pharmaceutical firm, belonged to a class of compounds, known as phenothiazines, that were developed in the late 1800s for use as synthetic dyes. In the 1930s, the U.S. Department of Agriculture employed phenothiazine compounds for use as an insecticide and to kill swine parasites. Then, in the 1940s, phenothiazines were found to sharply limit locomotor activity in mammals, but without putting them to sleep. Rats that had learned to climb ropes in order to avoid painful electric shocks could no longer perform this escape task when administered phenothiazines. This effect inspired investigations by French researchers into whether phenothiazines could be used during surgery to enhance the effects of barbiturates and other anesthetics—perhaps phenothiazines could numb the central nervous system in a novel way. Rhône-Poulenc experimented with various phenothiazine derivatives before selecting chlorpromazine as one that might best achieve this numbing effect.

In 1951, French naval surgeon Henri Laborit tested chlorpromazine on surgical patients and found that it worked so well operations could be performed with almost no anesthesia. He also observed that it put patients into an odd “twilight” state. They would become emotionally detached and disinterested in anything going on around them, yet able to answer questions. One of Laborit’s colleagues likened this effect to a “veritable medicinal lobotomy,” an observation that suggested it might have use in psychiatry.⁴

A year later, French psychiatrists Jean Delay and Pierre Deniker announced that they had used it to calm manic patients at St. Anne’s Hospital in Paris. It was just as Laborit had said. Chlorpromazine induced in patients a profound indifference. They felt separated from the world “as if by an invisible wall.”

Seated or lying down, the patient is motionless on his bed, often pale and with lowered eyelids. He remains silent most of the time. If questioned, he responds after a delay, slowly, in an indifferent monotone, expressing himself with few words and quickly becoming mute. Without exception, the response is generally valid and pertinent, showing that the patient is capable of attention and of reflection. But he rarely takes the initiative of asking a question; he does not express his preoccupations, desires, or preference. He is usually conscious of the amelioration brought on by the treatment, but he does not express euphoria. The apparent indifference or the delay in response to external stimuli, the emotional and affective neutrality, the decrease in both initiative and preoccupation without alteration in conscious awareness or in intellectual faculties constitute the psychic syndrome due to the treatment.⁵

Delay and Deniker dubbed their new treatment “hibernation therapy.” Other European psychiatrists soon found it useful for the same reason. Chlorpromazine, they announced, produced a “vegetative syndrome” in patients. Psychotic patients on chlorpromazine became “completely immobile” and could be “moved about like puppets.” British psychiatrist D. Anton-Stephens found that drugged patients “couldn’t care less” about anything around them and would lie “quietly in bed, staring ahead”—a bother to no one in this drugged state.⁶

The first psychiatrist in North America to test chlorpromazine was Heinz Lehmann, at Verdun Protestant Hospital in Montreal. Like his European peers, Lehmann speculated that it “may prove to be a pharmacological substitute for lobotomy.” Medicated patients became “sluggish,” “apathetic,” “disinclined to walk,” less “alert,” and had an empty look—a “vacuity of expression”—on their faces. They spoke in “slow monotones.” Many complained that chlorpromazine made them feel “empty” inside, Lehmann noted. “Some patients dislike the treatment and complain of their drowsiness and weakness. Some state that they feel ‘washed out,’ as after an exhausting illness, a complaint which is indeed in keeping with their appearance.”⁷

U.S. psychiatrists initially perceived chlorpromazine’s effects this way as well. The drug, wrote Philadelphia psychiatrist N. William Winkelman Jr., transformed patients. Those “who had been severely agitated, anxious and belligerent became immobile, waxlike, quiet, relaxed and emotionally indifferent.”⁸ Texas psychiatrist Irvin Cohen reported: “Apathy, lack of initiative and loss of interest in surroundings are a common response in patients.”⁹ In 1955, Deniker and Delay coined the term “neuroleptic” to describe the effects produced by chlorpromazine and other phenothiazines that had been introduced. The word came from the Greek, meaning to “take hold of the nervous system,” reflective of how the drugs were perceived to act as chemical restraints.

Very early on, physicians in Europe and the United States realized that chlorpromazine frequently induced Parkinson’s disease symptoms—the shuffling gait, the masklike visage, and even the drooling. Swiss psychiatrist Hans Steck announced in 1954 that 37 percent of the 299 mental patients he’d treated with chlorpromazine showed signs of Parkinson’s.¹⁰ Lehmann noticed the same thing. In the United States, more than 100 psychiatrists who met in Philadelphia in June 1955 spoke at great length about this side effect. “Our feeling has been that all patients who are on large doses of Thorazine for any length of time show some signs of basal ganglion dysfunction,” noted George Brooks, from Vermont State Hospital. “Not perhaps full-blown Parkinsonism, but some loss of associated movements, loss of facial mobility, etc.” Hyman Pleasure, a psychiatrist from Pilgrim State Hospital in New York, reported the same findings: “Probably two-thirds of our patients showed some degree of Parkinson-like symptoms.” Added Delaware State Hospital psychiatrist Fritz Freyhan: Chlorpromazine can “metamorphose a highly mobile, flighty manic into a static, slow-motion shuffler.”¹¹

Indeed, Freyhan and others at the 1955 meeting debated whether such symptoms should be deliberately induced. Many observed that the best therapeutic results, in terms of producing an emotional tranquillity in patients, coincided with the appearance of the motor disability. This led some to speculate that Parkinson’s was somehow antagonistic to schizophrenia, much in the same way that convulsions had once been thought to chase away the disorder. If so, the proper therapeutic dosage would be one that induced this motor disability, and then perhaps the symptoms of this disease could be controlled with other drugs. Winfred Overholser, superintendent of St. Elizabeth’s Hospital in Washington, D.C., closed the Philadelphia symposium with this question for his peers: “Should you push the drug to the stage of bringing about Parkinsonism? Is it a fact that the ratio of improvement or symptomatic recovery is greater in the cases in which Parkinsonism is developed?”¹²

During this initial period, psychiatrists did not perceive chlorpromazine as having any specific antipsychotic properties. “It is important to stress that in no case was the content of the psychosis changed,” wrote England’s Joel Elkes, in 1954. “The schizophrenic and paraphrenic patients continued to be subject to delusions and hallucinations, though they appeared to be less disturbed by them.”¹³ Instead, neuroleptics were perceived to “work” by hindering brain function. Chlorpromazine, Lehmann observed, has the “remarkable property of inhibiting lower functional centers of the central nervous system without significantly impairing the function of the cortex.”¹⁴ Laborit said that the drug’s principal therapeutic effect was the “disconnection of the neurovegetative system.”¹⁵ Animal experiments showed that lesions in the caudal hypothalamus produced similar deficiencies in motor skills and initiative. Neuroleptics, researchers concluded, “modified” patients in ways that made their behavior more acceptable to others. They could be used “to attain a neuropharmacologic effect, not to ‘cure’ a disease.”¹⁶

By 1957, Delay and Deniker had also recognized that neuroleptics produced deficits similar to those caused by encephalitis lethargica. This ailment, which struck 5 million people worldwide during a 1916-1927 epidemic, caused a brain inflammation that left people apathetic, lacking the will to do anything, and with waxlike facial expressions. Physicians described the disease, known colloquially as sleeping sickness, as causing “psychomotor inertia.” Chlorpromazine caused eerily similar deficits, only at a much faster pace. Deniker wrote: “It was found that neuroleptics could experimentally reproduce almost all the symptoms of lethargic encephalitis. In fact, it would be possible to cause true encephalitis epidemics with the new drugs.”¹⁷

Although it might seem strange today that a drug described in this manner would be welcomed into the state mental hospitals, at the time such effects were seen as desirable. In the early 1950s, insulin coma, electroshock, and frontal lobotomy were all perceived as helpful therapies. The asylum conditions that had led to those earlier brain-disabling therapies being declared effective—did they make patients quieter, easier to manage, and less hostile?—were also still in place. In 1954, hospital administrators were still struggling with horribly inadequate budgets and hopelessly overcrowded facilities. A drug that could reliably tranquilize disruptive patients was bound to be welcomed. Hospital staff—much in the same way they had felt more kindly toward patients reduced to childlike behavior by insulin coma—even felt more empathetic toward their patients once they were stilled by chlorpromazine.

“Chlorpromazine [has] produced a decrease in brutality in mental hospitals which was not achievable by any system of supervision or control of personnel,” declared Anthony Sainz of Marcy State Hospital in New York. “Many patients, for example, when they develop a central ganglionic or Parkinsonian syndrome become more ‘sick’ and thus arouse the sympathies of those taking care of them instead of arousing their anger and hostility. The patients, in consequence, receive better care rather than worse.”¹⁸

Chlorpromazine, then, initially found a place within asylum medicine. However, even as it was making its debut in that environment, the United States was in the first stage of rethinking its care of the mentally ill and envisioning a change that would, at least in theory, require a pill different in kind from chlorpromazine. With eugenics now a shamed science, there was no longer the same societal belief that the mentally ill necessarily needed to be segregated, and yet the states were still stuck with the financial consequences of that eugenics legacy. There were more than 500,000 people in public mental institutions, and even though states were still scrimping on expenses, spending less than $2 per day per patient (less than one-seventh the amount spent in general hospitals), their collective expenditures for the mentally ill had reached $500 million annually. They wanted to get out from under that expensive burden, and in the early 1950s, the Council of State Governments, which had been meeting annually to discuss this problem, articulated a vision of reform. “There are many persons in state hospitals who are not now in need of continuing psychiatric hospital care,” the council announced. “Out-patient clinics should be extended and other community resources developed to care for persons in need of help, but not of hospitalization.”¹⁹

America had a new agenda on the table, replacing asylum care with community care. But for that agenda to proceed, America would need to believe that a medical treatment was available that would enable the seriously mentally ill to function in the community. The neuroleptics that had been embraced in asylum medicine—drugs that reliably made patients lethargic, emotionally disengaged, and retarded in movement—hardly fit that bill. A pill of a different sort would be needed, and so it was, with that fiscal agenda on the table, that neuroleptics, over the course of ten years, underwent a remarkable transformation.

Spinning Dross into Gold

In one manner or another, mad medicine is always shaped by larger forces coursing through a society. The brain-damaging somatic therapies of the 1930s—insulin coma, electroshock, and lobotomy—all appeared in asylum medicine while American society was under the influence of eugenics. Chlorpromazine made its debut as a successor to those therapies, and then its image was transformed in a society newly under the influence of pharmaceutical money.

After World War II, global leadership in drug development began to shift from Germany to the United States, and it did so because the financial opportunities in the United States were so much greater. Drug manufacturers in the United States could get FDA approval for their new medications with relative ease, since at that time they did not have to prove that their drugs were effective, only that they weren’t too toxic. They could also charge much higher prices for their drugs in the United States than in other countries because of strong patent-protection laws that limited competition. Finally, they could count on the support of the influential American Medical Association, which, as a result of a new law, had begun cozying up to the pharmaceutical industry.

Prior to 1951, the AMA had acted as a watchdog of the drug industry. In the absence of government regulations requiring pharmaceutical companies to prove that their medications had therapeutic merit, the AMA, for nearly fifty years, had assumed the responsibility of distinguishing good drugs from the bad. It had its own drug-testing laboratory, with drugs deemed worthwhile given the AMA seal of approval. Each year it published a book listing the medications it found useful. Drug companies were not even allowed to advertise in the Journal of the American Medical Association unless their products had been found worthy of the AMA seal. At that time, however, patients could obtain most drugs without a doctor’s prescription. Drug companies primarily sold their goods directly to the public or through pharmacists. Physicians were not, in essence, drug vendors. But in 1951, Minnesota senator Hubert Humphrey cosponsored a bill, which became the Durham-Humphrey Amendment to the Federal Food, Drug and Cosmetics Act of 1938, that greatly expanded the list of medications that could be obtained only with a doctor’s prescription. While the amendment was designed to protect the public by allowing only the safest of drugs to be sold over the counter, it also provided doctors with a much more privileged status within society. The selling of nearly all potent medications now ran directly through them. As a result, drug companies began showering them, and their professional organizations, with their marketing dollars, and that flow of money changed the AMA almost overnight.

In 1950, the AMA received $5 million from member dues and journal subscriptions but only $2.6 million from drug-company advertisements in its journals. A decade later, its revenue from dues and subscriptions was still about the same ($6 million), but the money it received from drug companies had leaped to $10 million—$8 million from journal advertisements and another $2 million from the sale of mailing lists. As this change occurred, the AMA dropped its critical stance toward the industry. It stopped publishing its book on useful drugs, abandoned its seal-of-approval program, and eliminated its requirement that pharmaceutical companies provide proof of their advertising claims. In 1961, the AMA even opposed a proposal by Tennessee senator Estes Kefauver to require drugmakers to prove to the Food and Drug Administration (FDA) that their new drugs were effective. As one frustrated physician told Kefauver, the AMA had become a “sissy” to the industry.²⁰

But it wasn’t just the AMA that was being corrupted. Starting in 1959, Kefauver directed a two-year investigation by the Senate Subcommittee on Antitrust and Monopoly into drug-industry practices, and his committee documented how the marketing machinery of pharmaceutical firms completely altered what physicians, and the general public, read about new medications. Advertisements in medical journals, the committee found, regularly exaggerated the benefits of new drugs and obscured their risks. The “scientific” articles provided a biased impression as well. Prominent researchers told Kefauver that many medical journals “refused to publish articles criticizing drugs and methods, lest advertising suffer.” Pfizer physician Haskell Weinstein confessed that pharmaceutical companies ghostwrote many of the laudatory articles:

A substantial number of the so-called medical scientific papers that are published on behalf of these drugs are written within the confines of the pharmaceutical houses concerned. Frequently the physician involved merely makes the observations and his data, which sometimes are sketchy and uncritical, are submitted to a medical writer employed by the company. The writer prepares the article which is returned to the physician who makes the overt effort to submit it for publication. The article is frequently sent to one of the journals which looks to the pharmaceutical company for advertising and rarely is publication refused. The particular journal is of little interest inasmuch as the primary concern is to have the article published any place in order to make reprints available. There is a rather remarkable attitude prevalent that if a paper is published then its contents become authoritative, even though before publication the same contents may have been considered nonsense.²¹

In its 1961 report, Kefauver’s committee also detailed how pharmaceutical companies manipulated the popular press. Magazines were promised advertising revenues if they would publish features mentioning a company’s drug in a positive light. Writers could earn extra fees on the side for doing the same, with one scribe telling of a potential payoff of $17,000—far more than a year’s salary at the time—for a single magazine article. Writers were also bribed with free dinners, limousine rides, and other perks. Weinstein told Kefauver’s committee that, as with the scientific literature, “much of what appears (in the popular press) has in essence been placed by the public relations staffs of the pharmaceutical firms. A steady stream of magazine and newspaper articles are prepared for distribution to the lay press.”²²

In short, in the 1950s, what American physicians and the general public learned about new drugs was molded, in large part, by the pharmaceutical industry’s marketing machine. This molding of opinion, of course, played a critical role in the recasting of neuroleptics as safe, antischizophrenic drugs for the mentally ill.

Smith, Kline & French obtained the rights to market chlorpromazine in the United States from Rhône-Poulenc in the spring of 1952. At that time, it wasn’t a large pharmaceutical house and had annual sales of only $50 million. While it foresaw many possible therapeutic uses for chlorpromazine, it wanted to get the drug on the market as quickly as possible and thus tested it primarily as an antivomiting agent. All told, the company spent just $350,000 developing the drug, administering it to fewer than 150 psychiatric patients for support of its new drug application to the FDA. “Let’s get this thing on the market as an anti-emetic,” reasoned the company’s president, Francis Boyer, behind closed doors, “and we’ll worry about the rest of that stuff later.”²³

The FDA approved chlorpromazine on March 26, 1954, and a few days later Smith Kline fired the first shot in its marketing campaign. It produced a national television show, titled “The March of Medicine,” and now it was time to craft a story of dutiful science at work. Thorazine, Boyer told the American public, had been rigorously tested:

It was administered to well over 5,000 animals and proved active and safe for human administration. We then placed the compound in the hands of physicians in our great American medical centers to explore its clinical value and possible limitations. In all, over 2,000 doctors in this country and Canada have used it . . . the development of a new medicine is difficult and costly, but it is a job our industry is privileged to perform.²⁴

The television show was the kickoff in an innovative, even brilliant plan for selling the drug. In order to woo state legislatures, which would need to allot funding for use of the drug in mental hospitals, Smith, Kline & French established a fifty-member task force, with each member assigned to a state legislature. The task force organized a “speakers’ training bureau” to coach hospital administrators and psychiatrists on what to say to the press and to state officials—a public message of a breakthrough medication needed to be woven. There would be no comments about chemical lobotomies or encephalitis lethargica. Instead, a story of lost lives being wonderfully restored would be told. The company also compiled statistics on how use of the drug would save states money in the long run—staff turnover at asylums would be reduced because handling the patients would be easier, facility maintenance costs would be decreased, and ultimately, at least in theory, many medicated patients could be discharged. This was a win-win story to be created—the patients’ lives would be greatly improved and taxpayers would save money.

With the company’s training bureau at work in this way, chlorpromazine underwent a step-by-step transformation in the popular press, and in the medical literature as well.

In June 1954, Time published its first article on chlorpromazine. At that point, the task force had just set up shop, and so the makeover of chlorpromazine’s image was still at an early stage. In an article titled “Wonder Drug of 1954?” Time reported:

After a few doses, says Dr. Charles Wesler Scull of Smith, Kline & French, patients who were formerly violent or withdrawn lie “molded to the bed.” When a doctor enters the room, they sit up and talk sense with him, perhaps for the first time in months. There is no thought that chlorpromazine is any cure for mental illness, but it can have great value if it relaxes patients and makes them accessible to treatment. The extremely agitated or anxious types often give up compulsive behavior, a surface symptom of their illness. It is, says Dr. Scull, as though the patients said, “I know there’s something disturbing me, but I couldn’t care less.”²⁵

While filled with praise for chlorpromazine, the article still did not describe medicated patients as being “cured” or walking about with great energy. This was still a chemical agent that “molded” patients to the bed and induced emotional indifference. But over the course of the next twelve months, as can be seen in coverage by the New York Times, the story being fed to the press changed. Researchers started hinting that chlorpromazine might be curative, a pill that quickly healed the mind and enabled people to go about their daily business in normal fashion.

In 1955, the New York Times reported on chlorpromazine at least eleven times. “New Cure Sought for Mentally Ill” ran one headline. “Drug Use Hailed in Mental Cases” said another. The theme repeated over and over was this: Chlorpromazine was “one of the most significant advances in the history of psychiatric therapy.” Hospitals using the drug were releasing patients “at a record rate.” This was a “miracle” pill that would make it possible for family doctors to treat mental illness in their offices, with “only the most seriously disturbed” needing to be hospitalized. Chlorpromazine brought the disturbed patient “peace of mind” and “freedom from confusion.” Virtually nothing was said about the drug’s side effects; not one of the eleven articles mentioned that it caused Parkinson’s symptoms or lethargy.²⁶ On June 26, 1955, New York Times medical writer Howard Rusk confidently declared that the neuroleptics had proven their worth:

Today, there can be little doubt that, in the use of these and other drugs under study, research has developed new tools that promise to revolutionize the treatment of certain mental illnesses. [The drugs] gradually calm patients, who then lose their fear and anxiety and are able to talk about their troubles more objectively. Patients do not develop the lethargy that follows the use of barbiturates . . . there is no doubt of the effectiveness of these new drugs in either curing or making hitherto unreachable patients amenable to therapy. (italics added)²⁷

Psychiatric researchers also saw an opportunity to use this tale of medical progress to lobby Congress for increased research funds. In May 1955, Nathan Kline, Henry Brill, and Frank Ayd told a Senate budget committee that neuroleptics had given the field new hope. Thanks to the tranquilizers, they said, “patients who were formerly untreatable within a matter of weeks or months become sane, rational human beings.” Hospitalization could “be shortened, often avoided altogether.” Their lobbying led U.S. News and World Report to announce that new “wonder drugs” were “promising to revolutionize the treatment of mental disease.”²⁸ Time even suggested that neuroleptics marked a medical advance as profound as the “germ-killing sulfas discovered in the 1930s.” Physicians who resisted using them, it added, were “ivory-tower critics” who liked to waste their time wondering whether a patient “withdrew from the world because of unconscious conflict over incestuous urges or stealing from his brother’s piggy bank at the age of five.”²⁹

Not surprisingly, with this storytelling at work, Congress coughed up. Federal spending on mental-health research rose from $10.9 million in 1953 to $100.9 million in 1961—a tenfold increase in eight years. The storytelling also gave state legislators real hope that community care could replace hospital care. At the governors’ conference in 1955, the states pledged support “for a full-scale national survey on the status of mental illness and health in the light of new concepts and treatment methods.”³⁰ That same year, Congress passed the Mental Health Study Act, which established the Joint Commission on Mental Illness and Mental Health to devise a plan for remaking the nation’s care of the mentally ill.

This image makeover of chlorpromazine in the lay press was being repeated, to some extent, in the medical literature. In the first decade after its approval, more than 10,000 articles in medical journals discussed it. Most were laudatory. And once a new public story began swirling around the drug, many investigators changed their first impressions. William Winkelman’s first two published reports illustrate this change.

In 1953, when Smith, Kline & French chose Winkelman to be its lead investigator on its initial tests of chlorpromazine, surgical lobotomy was still seen as a good thing. It was the therapy that chlorpromazine had to measure up to, and when Winkelman reported his initial results, in the Journal of the American Medical Association on May 1, 1954, he praised the drugs for being similar in kind. “The drug produced an effect similar to frontal lobotomy,” he said approvingly. It made patients “immobile,” “waxlike,” and “emotionally indifferent.”³¹ However, three years later, in a study of 1,090 patients published in the American Journal of Psychiatry, Winkelman painted a new picture. Motor dysfunction was suddenly nowhere to be found. In this large cohort of patients, followed for up to three years, Winkelman said that he had “not seen a full-blown case of Parkinsonism.”³² Only two of the 1,090 patients even showed faint signs of this disorder, he said. This, of course, was a remarkable change from the talk at the Philadelphia symposium two years earlier, when one physician, Brooks from Vermont, had seen evidence of Parkinsonism in all of his patients. But it fit in well with the story being told in the popular press of hopeless patients suddenly being returned to normal, or, as in the case of the New York Times, the story of a drug that didn’t cause lethargy.

The AMA, meanwhile, also stepped in to ensure that this story of medical progress was not derailed.

There were any number of psychiatrists who were dismayed by the glowing reports of chlorpromazine in the press and medical literature. One, writing in the Nation, described it as “vulgarized falsity.”³³ Gregory Zilboorg, a prominent New York psychoanalyst, blasted the press, saying that the public was being egregiously misled and that the only real purpose of the drug was to make hospitalized patients easier to handle. “If I hit you over the head and make you bleary eyed,” he asked rhetorically, “will you understand me better?”³⁴ Yet another well-known physician, Lawrence Kolb, who had formerly directed the U.S. Public Health Services’ mental-hygiene division, called neuroleptics “physically more harmful than morphine and heroin.”³⁵ Such criticism made for an almost bizarre public confusion. Were neuroleptics wonder drugs or not? Even Kline and Ayd, who’d told their own wonder story to Congress, complained that drugmakers were making false claims in their advertisements and mailings. A House subcommittee decided to investigate, and it was then, with the industry on the hot seat, that the AMA rushed to its defense. Drug companies were acting responsibly with their advertisements, Dr. Lee Bartemeier, chairman of the AMA’s committee on mental health, told the House.³⁶ They were not heaping “extravagant and distorted literature” on the nation’s physicians. His testimony defused the matter, and no one put two and two together when, in the following months, the AMA launched Archives of General Psychiatry, its pages filled with advertisements for the new miracle drugs.

Smith, Kline & French could certainly afford the marketing expense. In 1958, Fortune magazine ranked it second among 500 American industrial corporations in terms of highest “net profit after taxes on invested capital,” with its whopping return of 33.1 percent. Its high profit margins reflected the fact that it was charging $3.03 for a bottle of chlorpromazine, six times what Rhône-Poulenc, the inventor of the drug, could charge in France.³⁷ Some states were now spending approximately 5 percent of their mental-hospital budgets for Thorazine. Indeed, Smith, Kline & French’s payoff from its $350,000 investment in chlorpromazine was one for the record books. The company’s revenues skyrocketed from $53 million in 1953 to $347 million in 1970, with Thorazine contributing $116 million that year alone.³⁸

The Delusion Is Complete

In early 1963, President John Kennedy unveiled his plan for reforming the nation’s care of the mentally ill. The state hospitals, relics from a shameful past, would be replaced by a matrix of community care, anchored by neighborhood clinics. At the heart of this vision, the medical advance that made it possible, were the neuroleptics. Two years earlier, Kennedy had received the recommendations of the Joint Commission on Mental Illness and Mental Health, and in that report the drugs had been described as having “delivered the greatest blow for patient freedom, in terms of non-restraint, since Pinel struck off the chains of the lunatics in the Paris asylum 168 years ago . . . In the surprising, pleasant effects they produce on patient-staff relationships, the drugs might be described as moral treatment in pill form.”³⁹ Kennedy drove home the point for the American people: The new drugs made “it possible for most of the mentally ill to be successfully and quickly treated in their own communities and returned to a useful place in society.”⁴⁰

Two critical studies had put the final stamp of science on this belief. The first consisted of a series of reports by Henry Brill and Robert Patton, employees of the New York State Department of Mental Hygiene, assessing whether neuroleptics had led to a decline in the patient census at the state’s mental hospitals. Nationwide, the patient census had declined from 558,600 in 1955 to 528,800 in 1961. In New York, the census had dropped from 93,314 in 1955 to 88,764 in 1960—evidence, many argued, that the neuroleptics were helping people get well. However, as Brill and Patton acknowledged, isolating neuroleptics as the specific cause of that slight decline was quite difficult. Hospitalization rates for the mentally ill always reflect social policies—should the mentally ill be quarantined or not?—and by 1954, states were shouting that the patient census needed to drop. New York and many other states, in fact, had begun developing community care initiatives in the early 1950s, funneling the mentally ill into nursing homes, halfway houses, and sheltered workshops. In spite of these confounding factors, Brill and Patton concluded that neuroleptics must have played at least some role in the decline, since the drop in census, however slight, coincided with the introduction of neuroleptics. The fact that the two occurred at the same time was seen as the proof.⁴¹

Their work became widely cited, and was much discussed by the Joint Commission in its report. But in their research, Brill and Patton hadn’t compared discharge rates for drug-treated versus nontreated patients, a shortcoming that became evident when investigators at California’s mental hygiene department did precisely that. In a study of 1,413 first-episode male schizophrenics admitted to California hospitals in 1956 and 1957, they found that “drug-treated patients tend to have longer periods of hospitalization . . . furthermore, the hospitals wherein a higher percentage of first-admission schizophrenic patients are treated with these drugs tend to have somewhat higher retention rates for this group as a whole.”⁴² In short, the California investigators determined that neuroleptics, rather than speeding people’s return to the community, apparently hindered recovery. But it was the Brill and Patton research that got all of the public attention. Their conclusions supported the story that the public wanted to hear.

The second study that made Kennedy’s plan seem feasible was a multi-site trial of neuroleptics led by the National Institute of Mental Health (NIMH). While the medical journals in the 1950s may have filled up with articles lauding the new drugs, the research behind the articles was recognized as mostly pap: Few convincing placebo-controlled, double-blind studies—a trial design that had come to be recognized as a standard for good drug research—had been conducted. In 1961, the NIMH launched a nine-hospital study, evaluating outcomes in newly admitted patients over a six-week period, to remedy this deficiency. The announced results were stunning. None of the 270 drug-treated schizophrenics became worse, 95 percent improved somewhat, and nearly 50 percent improved so dramatically that they could be classified as either “normal” or only “borderline ill.” Indeed, the NIMH-FUNDED investigators concluded that chlorpromazine and two other neuroleptics reduced apathy, improved motor movement, and made patients less indifferent—precisely the opposite conclusions drawn by their peers a decade earlier. Side effects, meanwhile, were said to be “mild and infrequent . . . more a matter of patient comfort than of medical safety.” Most convincing of all, the NIMH determined that the drugs were indeed curative: “Almost all symptoms and manifestations characteristic of schizophrenic psychoses improved with drug therapy, suggesting that the phenothiazines should be regarded as ‘antischizophrenic’ in the broad sense. In fact, it is questionable whether the term ‘tranquilizer’ should be retained.”⁴³

The transformation of the neuroleptics was now complete. A drug that when first introduced was described as a chemical lobotomy, useful for making patients sluggish and emotionally indifferent, had become a safe and effective medication for schizophrenia. And that clearly is what the psychiatrists who participated in the NIMH trial now honestly saw. Their perceptions had changed in ways that matched societal goals and the story fashioned by drug companies over the past decade. Pharmaceutical ads, the flood of published articles in the scientific literature, the many stories in the popular media of miracle drugs—all had told of drugs that could heal the mentally disturbed. That was the belief that had been crafted, and, in the NIMH trial, the investigators had made observations consistent with it. They saw, in the altered behavior of their medicated patients, the image of their own expectations.

It was also a “reality” that worked for many. The states had wanted to shed the financial burden of their public mental hospitals, and now a scientific rationale was in place for discharging patients into the community. Psychiatry could now pride itself on having become a fully modern discipline, able to offer patients curative pills. Pharmaceutical companies, meanwhile, could count on states to set up programs focused on medicating discharged patients. Rather than serving as a short-term remedy for calming manic patients, neuroleptics were now medications that needed to be taken continuously. Pharmaceutical firms had lifelong customers for their drugs, and a society poised to insist that such drugs be taken. Finally, in this optimistic time of Kennedy’s Camelot, American society could believe it was righting yet another social abuse from the past. The mentally ill, so long neglected, would now be welcomed into the community. As Wilbur Cohen, acting secretary of the Department of Health, Education and Welfare, said a few years later, many among the mentally ill “can be put back to work and can be given a rightful place in society, and they are not a drain on either their families or the taxpayer.”⁴⁴

Unfortunately, it was a good-news tale that was missing one key voice: that of the mentally ill. There had been little mention of how they felt about these wonder drugs. It was a glaring absence, and, as usual, their perceptions were quite at odds with society’s belief that a safe “antischizophrenic” treatment had been found. There were different realities at work, and that set the stage for those deemed mad in America to suffer in new and novel ways.