Anatomy of an Epidemic (9 page)

But it wasn’t just that the AMA had given up its watchdog role. The AMA and physicians were also now working with the pharmaceutical industry to promote new drugs. In 1951, the year that the Durham-Humphrey Act was passed, Smith Kline and French and the American Medical Association began jointly producing a television program called
The March of Medicine
, which, among other things, helped introduce Americans to the “wonder” drugs that were coming to market. Newspaper and magazine articles about new medications inevitably included testimonials from doctors touting their benefits, and as Pfizer physician Haskell Weinstein later confessed to a congressional committee, “much of what appears [in the popular press] has in essence been placed by the public relations staffs of the pharmaceutical firms.”
¹⁷
In 1952, an industry trade publication,
FDC Reports
, noted that the pharmaceutical industry was enjoying a “sensationally favorable press,” and a few years later, it commented on why this was so. “Virtually all important drugs,” it wrote, receive “lavish praise by the medical profession on introduction.”
¹⁸

This new marketplace for drugs proved profitable for all involved. Drug industry revenues topped $1 billion in 1957, the pharmaceutical companies enjoying earnings that made them “the darlings of Wall Street,” one writer observed.
¹⁹
Now that physicians controlled access to antibiotics and all other prescription drugs, their incomes began to climb rapidly, doubling from 1950 to 1970 (after adjusting for inflation). The AMA’s revenues from drug advertisements in its journals rose from $2.5 million in 1950 to $10 million in 1960, and not surprisingly, these advertisements painted a rosy picture. A 1959 review of drugs in six major medical journals found that 89 percent of the ads provided no information about the drugs’ side effects.
²⁰

Such was the environment in the 1950s when the first psychiatric drugs were brought to market. The public was eager to hear of wonder drugs, and this was just the story that the pharmaceutical industry and the nation’s physicians were eager to tell.

Smith Kline and French, which obtained a license from Rhône-Poulenc to sell chlorpromazine in the United States, secured FDA approval for Thorazine on March 26, 1954. A few days later, the company used its
March of Medicine
show to launch the product. Although Smith Kline and French had spent only $350,000 developing Thorazine, having administered it to fewer than 150 psychiatric patients prior to submitting its application to the FDA, the company’s president, Francis Boyer, told viewers that this was a product that had gone through the most rigorous testing imaginable. “It was administered to well over five thousand animals and proved active and safe for human administration,” he said. “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 two thousand 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.”
²¹

Boyer’s was a story of rigorous science at work, and less than three months later,
Time
, in an article titled “Wonder Drug of 1954?,” pronounced Thorazine a “star performer.” After a dose of Thorazine, the magazine explained, patients “sit up and talk sense with [the doctor], perhaps for the first time in months.”
²²
In a follow-up article,
Time
reported that patients “willingly took [the] pills” and that once they did, they “fed themselves, ate heartily and slept well.” Thorazine, the magazine concluded, was as important “as the germ-killing sulfas discovered in the 1930s.”
²³

This was a magic-bullet reference that was impossible to miss, and other newspapers and magazines echoed that theme. Thanks to chlorpromazine,
U.S. News and World Report
explained, “patients who were formerly untreatable within a matter of weeks or months become sane, rational human beings.”
²⁴
The
New York Times
, in a series of articles in 1954 and 1955, called Thorazine a “miracle” pill that brought psychiatric patients “peace of mind” and “freedom
from confusion.” Thorazine, newspapers and magazines agreed, had ushered in a “new era of psychiatry.”
²⁵

With such stories being told about Thorazine, it was little wonder that the public went gaga when Miltown, in the spring of 1955, was introduced into the market. This drug,
Time
reported, was for “walk-in neurotics rather than locked-in psychotics,” and according to what psychiatrists were telling newspaper and magazine reporters, it had amazing properties.
²⁶
Anxiety and worries fled so quickly,
Changing Times
explained, that it could be considered a “happy pill.”
Reader’s Digest
likened it to a “Turkish bath in a tablet.” The drug, explained
Consumer Reports
, “does not deaden or dull the senses, and it is not habit forming. It relaxes the muscles, calms the mind, and gives people a renewed ability to enjoy life.”
²⁷

The public rush to obtain this new drug was such that Wallace Laboratories and Carter Products, which were jointly selling meprobamate, struggled to keep up with the demand. Drugstores lucky enough to have a supply put out signs that screamed:
YES
,
WE HAVE MILTOWN
! The comedian Milton Berle said that he liked the drug so much that he might change his first name to Miltown. Wallace Laboratories hired Salvador Dalí to help stoke Miltown fever, paying the great artist $35,000 to create an exhibit at an AMA convention that was meant to capture the magic of this new drug. Attendees walked into a darkened claustrophobic tunnel that represented the interior of a caterpillar—this was what it was like to be anxious—and then, as they emerged back into the light, they came upon a golden “butterfly of tranquility,” this metamorphosis due to meprobamate. “To Nirvana with Miltown” is how
Time
described Dalí’s exhibit.
²⁸

There was one slightly hesitant note that appeared in newspaper and magazine articles during the introduction of Thorazine and Miltown. In the 1950s, many of the psychiatrists at top American medical schools were Freudians, who believed that mental disorders were caused by psychological conflicts, and their influence led Smith Kline and French, in its initial promotion of Thorazine, to caution reporters that “there is no thought that chlorpromazine is a cure for mental illness, but it can have great value if it relaxes patients and
makes them accessible to treatment.”
²⁹
Both Thorazine and Miltown, explained the
New York Times
, should be considered as “adjuncts to psychotherapy, not the cure.”
³⁰
Thorazine was called a “major tranquilizer” and Miltown a “minor tranquilizer,” and when Hoffmann-La Roche brought iproniazid to market, it was described as a “psychic energizer.” These drugs, although they may have been remarkable in kind, were not antibiotics for the mind. As
Life
magazine noted in a 1956 article titled “The Search Has Only Started,” psychiatry was still in the early stages of its revolution, for the “bacteria” of mental disorders had yet to be discovered.
³¹

Yet, in very short order, even this note of caution went by the wayside. In 1957, the
New York Times
reported that researchers now believed that iproniazid might be a “potent regulator of unbalanced cerebral metabolism.”
³²
This suggested that the drug, which had been developed to fight tuberculosis, might be fixing something that was wrong in the brains of depressed patients. A second drug for depressed patients, imipramine, arrived on the market during this time, and in 1959 the
New York Times
called them “antidepressants” for the first time. Both appeared to “reverse psychic states,” the paper said.
³³
These drugs were gaining a new status, and finally psychiatrist Harold Himwich, in a 1958 article in
Science
, explained that they “may be compared with the advent of insulin, which counteracts symptoms of diabetes.”
³⁴
The antidepressants were fixing something wrong in the brain, and when Hoffmann-La Roche brought Librium to market in 1960, it picked up on this curative message. Its new drug was not just another tranquilizer, but rather “the successor to this entire group…. Librium is the biggest step yet toward
‘pure’ anxiety relief
as distinct from central sedation or hypnotic action.”
³⁵
Merck did the same, marketing its drug Suavitil as “a mood normalizer…. Suavitil offers a new and specific type of neurochemical treatment for the patient who is disabled by anxiety, tension, depression, or obsessive-compulsive manifestations.”
³⁶

The final step in this image makeover of the psychiatric drugs came in 1963. The NIMH had conducted a six-week trial of Thorazine and other neuroleptics, and after these drugs were shown to be more effective than a placebo in knocking down psychotic
symptoms, the researchers concluded that that the drugs should be regarded “as antischizophrenic in the broad sense. In fact, it is questionable whether the term ‘tranquilizer’ should be retained.”
³⁷

With this pronouncement by the NIMH, the transformation of the psychiatric drugs was basically complete. In the beginning, Thorazine and other neuroleptics had been viewed as agents that made patients quieter and emotionally indifferent. Now they were “antipsychotic” medications. Muscle relaxants that had been developed for use in psychiatry because of their “taming” properties were now “mood normalizers.” The psychic energizers were “antidepressants.” All of these drugs were apparently antidotes to specific disorders, and in that sense, they deserved to be compared to antibiotics. They were disease-fighting agents, rather than mere tonics. All that was missing from this story of magic-bullet medicine was an understanding of the biology of mental disorders, but with the drugs reconceived in this way, once researchers came to understand how the drugs affected the brain, they developed two hypotheses that, at least in theory, filled in this gap.

At the start of the 1950s, there was an ongoing debate among neurologists about how signals crossed the tiny synapses that separated neurons in the brain. The prevailing view was that the signaling was electrical in kind, but others argued for chemical transmission, a debate that historian Elliot Valenstein, in his book
Blaming the Brain
, characterized as the “war between the sparks and the soups.” However, by the mid-1950s, researchers had isolated a number of possible chemical messengers in the brains of rats and other mammals, including acetylcholine, serotonin, norepinephrine, and dopamine, and soon the “soup” model had prevailed.

With that understanding in place, an investigator at the NIMH, Bernard Brodie, planted the intellectual seed that grew into the theory that depression was due to a chemical imbalance in the brain. In 1955, in experiments with rabbits, Brodie reported that reserpine,
an herbal drug used in India to quiet psychotic patients, lowered brain levels of serotonin. It also made the animals “lethargic” and “apathetic.” Arvid Carlsson, a Swedish pharmacologist who had worked for a time in Brodie’s lab, soon reported that reserpine also reduced brain levels of norepinephrine and dopamine (which jointly are known as catecholamines). Thus, a drug that depleted serotonin, norepinephrine, and dopamine in the brain seemed to make animals “depressed.” However, investigators discovered that if animals were pretreated with iproniazid or imipramine before they were given reserpine, they didn’t become lethargic and apathetic. The two “antidepressants,” in one manner or another, apparently blocked reserpine’s usual depletion of serotonin and the catecholamines.
³⁸

During the 1960s, scientists at the NIMH and elsewhere figured out how iproniazid and imipramine worked. The transmission of signals from the “presynaptic” neuron to the “postsynaptic” neuron needs to be lightning fast and sharp, and in order for the signal to be terminated, the chemical messenger must be removed from the synapse. This is done in one of two ways. Either the chemical is metabolized by an enzyme and shuttled off as waste, or else it flows back into the presynaptic neuron. Researchers discovered that iproniazid thwarts the first process. It blocks an enzyme, known as monoamine oxidase, that metabolizes norepinephrine and serotonin. As a result, the two chemical messengers remain in the synapse longer than normal. Imipramine inhibits the second process. It blocks the “reuptake” of norepinephrine and serotonin by the presynaptic neuron, and thus, once again, the two chemicals remain in the synapse longer than normal. Both drugs produce a similar end result, although they do so by different means.

In 1965, the NIMH’s Joseph Schildkraut, in a paper published in the
Archives of General Psychiatry
, reviewed this body of research and set forth a chemical imbalance theory of affective disorders:

Although this hypothesis had its obvious limitations—it was, Schildkraut said, “at best a reductionistic oversimplification of a very complex biological state”—the first pillar in the construction of the doctrine known today as “biological psychiatry” had been erected. Two years later, researchers erected the second pillar: the dopamine hypothesis of schizophrenia.