Anatomy of an Epidemic (42 page)

L. Ron Hubbard, a science-fiction writer, founded the Church of Scientology in 1952. One of the church’s core tenets is that the earth is populated by souls that previously lived on other planets, an “extraterrestrial” creation myth that could have been lifted directly from a sci-fi novel. In addition, Hubbard had his own ideas about how to heal the mind. Prior to founding Scientology, he had published
Dianetics: The Modern Science of Mental Health
, which outlined the use of an “auditing” process to eliminate painful past experiences from the mind. The scientific and medical community ridiculed dianetics as quackery and dismissed Hubbard as a huckster, and he in turn developed an intense hatred for psychiatry. In 1969, Scientology and Thomas Szasz cofounded the Citizens Commission on Human Rights, and this group began waging campaigns against lobotomy, electroshock, and psychiatric drugs.

This proved to be very fortuitous for the APA and its storytelling partners as they raised the flag of biological psychiatry. Indeed, it is easy to imagine the drug companies deciding to secretly fund Scientology’s protests, eager as they were to shove money to any organization that would—wittingly or unwittingly—advance their cause. For not only did Scientologists believe in extraterrestrials, they also had gained a reputation for being a secretive, litigious, and even
malevolent cult. Scientology,
Time
wrote in 1991, is a “hugely profitable global racket that survives by intimidating members and critics in a Mafia-like manner.”
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Thanks to Scientology, the powers that be in psychiatry had the perfect storytelling foil, for they could now publicly dismiss criticism of the medical model and psychiatric drugs with a wave of the hand, deriding it as nonsense that arose from people who were members of a deeply unpopular cult, rather than criticism that arose from their own research. As such, the presence of Scientology in the storytelling mix served to taint all criticism of the medical model and psychiatric drugs, no matter what its source.

Those were the storytelling forces that formed in the 1980s. When Prozac arrived on the market, they were lined up perfectly for the creation—and maintenance—of a tale about psychiatry’s great new leap.

During the 1920s, owners of radios in the heartland of America regularly tuned into station KFKB, which had perhaps the most powerful signal in the country at that time, even though it emanated from tiny Milford, Kansas. “This is Dr. John R. Brinkley greeting his friends in Kansas and everywhere,” they’d hear, and Dr. Brinkley did indeed have a most amazing story to tell. In 1918, he had begun transplanting goat gonads into the testicles of older men worried about their declining virility, a fifteen-minute operation, he told KFKB listeners, that had been proven to “completely restore” sexual prowess. “A man is as old as his glands,” the good doctor would explain, and this rejuvenating surgery worked because the goat tissue “blends with and nourishes the human tissue, stimulating the human gland to new activity.”
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Although Brinkley’s medical credentials were of a dubious sort—he had a degree from Eclectic Medical University of Kansas City, a diploma mill—he was a masterful storyteller and something of an advertising genius. After his first few operations, he told his story to newspapers in Kansas, and soon they were publishing pictures of him cradling the first “goat-gland baby,” the offspring of an older man who had undergone the operation. Older men began pouring
into Milford, each paying $750 for the procedure, and Brinkley cranked up his publicity machine. He hired three press agents to write ready-to-print newspaper features, which were then distributed to “publications interested in popularizing the latest developments from the laboratories of science.” Naturally, these planted articles included testimonials from satisfied customers, such as J. J. Tobias, chancellor of Chicago Law School, who—the articles said—liked to pound his chest and shout: “I’m a new man! It’s one of the great things of the century!” Brinkley established his own “Scientific Press” and reported a “90% to 95% success rate” for his surgery, which, he explained, returned the body to a proper hormonal “balance.” Once he began broadcasting his story on KFKB in 1923, he became so famous that three thousand letters arrived at his Mil-ford hospital each day, and by the late 1920s, he was perhaps the wealthiest “doctor” in the United States.

Eventually, Dr. Brinkley earned a place in medical history as one of the great charlatans of all time, when the American Medical Association targeted him as a quack. But when it came to marketing his goat-gonad surgery, he employed advertising techniques and a storytelling model that have stood the test of time. He published articles that appeared scientific, courted the press, claimed a very high success rate, offered a biological rationale for why the surgery worked, and provided reporters with quotes from satisfied customers. That—as Eli Lilly and other drug manufacturers can attest—is a tried-and-true formula for turning a psychiatric drug into a commercial success.

Today, the fraudulent nature of the story told by Eli Lilly and psychiatry about Prozac when it came to market is fairly well known, having been documented by Peter Breggin, David Healy, and Joseph Glenmullen, among others. Breggin and Healy wrote their accounts after gaining access to Eli Lilly files while serving as expert witnesses in civil lawsuits, which allowed them to see data and internal
memorandums that belied what the public had been told about the drug. At the risk of going over familiar ground, we need to revisit that story briefly, for it will help us see, with considerable clarity, how our societal delusions about the merits of the “second-generation” psychiatric drugs were formed. Eli Lilly’s marketing of Prozac proved to be a model that other companies followed as they brought their drugs to market, and it involved telling a false story in the scientific literature, hyping that story even more to the media, and hiding risks that could lead to disability and death for those who used the drugs.

Drug development begins in the laboratory, with investigation into a drug’s “mechanism of action,” and as we learned earlier, Eli Lilly scientists determind in the mid-1970s that fluoxetine caused serotonin to “pile up” in the synapse, which in turn triggered a series of physiological changes in the brain. Next, in animal studies, the drug was found to cause stereotyped activity in rats (repetitious sniffing, licking, etc.) and aggressive behavior in cats and dogs.
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In 1977, Eli conducted its first small trial in humans, but “none of the eight patients who completed the four-week treatment showed distinct drug-induced improvement,” Eli Lilly’s Ray Fuller told his colleagues in 1978. The drug also had caused “a fairly large number of reports of adverse reactions.” One patient had gone psychotic on the drug, and others had suffered from “akathisia and restlessness,” Fuller said.
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The trials of fluoxetine had barely begun and it was clear that Eli Lilly had a big problem. Fluoxetine didn’t appear to lift depression and it caused a side effect—akathisia—known to increase the risk of suicide and violence. After more reports of this kind came in, Eli Lilly amended its trial protocols. “In future studies, the use of benzodiazepines to control the agitation will be permitted,” Fuller wrote on July 23, 1979.
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The benzodiazepines would help suppress reports of akathisia, and likely boost efficacy results, as several trials of benzodiazepines for depression had shown them to be as effective as a tricyclic. Of course, as Eli Lilly’s Dorothy Dobbs later confessed
in court, the use of benzodiazepines was “scientifically bad,” as it would “confound the results” and “interfere with the analysis of both safety and efficacy,” but it enabled the company to continue development of fluoxetine.
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Still, even with addition of the benzodiazepines, fluoxetine failed to perform well. During the early 1980s, the company conducted a phase III trial of the drug in Germany, and in 1985, the German licensing authority, Bundesgesundheitsamt (BGA), concluded that this drug was “totally unsuitable for the treatment of depression.”
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According to the patients’ “self ratings” (as opposed to the doctors’ ratings), the drug produced “little response or no improvement in the clinical picture of the patients,” the BGA noted.
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At the same time, it had caused psychosis and hallucinations, and increased some patients’ anxiety, agitation, and insomnia, “which as adverse effects exceed those which are considered acceptable by medical standards,” the BGA wrote.
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Most problematic of all, this drug treatment could prove fatal. “Sixteen suicide attempts were made, two of these with success,” the BGA said.
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A German Eli Lilly employee privately calculated that the incidence rate of suicidal acts for the fluoxetine patients was “5.6 times higher than under the other active medication, imipramine.”
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With Germany having rejected its application, Eli Lilly naturally worried that it would be unable to gain FDA approval for fluoxetine.
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It needed to hide the suicide data, and in a 1994 civil lawsuit, Nancy Lord, an expert in clinical trial design, explained how the company did it. First, Eli Lilly instructed investigators to record various drug-related adverse events as “symptoms of depression.” As such, in the trial results submitted to the FDA, the problems were attributed to the disease rather than to fluoxetine. Second, when Eli Lilly scientists tabulated the data from case report forms, they changed individual reports of “suicidal ideation” to “depression.” Third, Lilly employees went through the German data “and pulled out [suicide] cases that they didn’t think were suicide.”
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All of these shenanigans, Lord told a court in 1994, made the entire testing process scientifically “worthless.” Yet even with these statistical manipulations, Eli Lilly still struggled to present a convincing case for fluoxetine in its application to the FDA. It had conducted placebo-controlled trials at eight sites, and in four of them, the fluoxetine patients had fared no better than the placebo group, and in the others, fluoxetine was only slightly better than a placebo.
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Meanwhile, when Peter Breggin reviewed Lilly’s documents, he discovered that imipramine had proven to be more effective than fluoxetine in six of seven trials.
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The FDA, in its March 28, 1985, review of one large trial, made the same observation: “Imipramine was clearly more effective than placebo, whereas fluoxetine was less consistently better than placebo.”
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At best, fluoxetine’s efficacy was of a very marginal sort, and FDA reviewer Richard Kapit also worried about its safety. At least thirty-nine patients treated with fluoxetine had gone psychotic in the short trials, and slightly more than 1 percent had become manic or hypomanic. Other side effects included insomnia, nervousness, confusion, dizziness, memory dysfunction, tremors, and impaired motor coordination. Fluoxetine, Kapit concluded, “may negatively affect patients with depression.”
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The FDA also understood that Eli Lilly had tried to hide many of these problems, the company having engaged in “large-scale underreporting” of the harm that fluoxetine could cause, according to reviewer David Graham.
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While the trials may have been scientifically worthless, they nevertheless proved to be an accurate forecast of what happened after Prozac was brought to market. There were numerous anecdotal accounts of Prozac-treated patients committing horrendous crimes or killing themselves, and so many adverse-events reports flowed into the FDA’s MedWatch program that Prozac quickly became America’s most complained about drug. By the summer of 1997, the FDA had received thirty-nine thousand such reports about Prozac, far outstripping the number received by any other drug for that nine-year period (1988–1997). The MedWatch filings told of hundreds of suicides, and of a long list of vexing side effects, which included psychotic depression, mania, abnormal thinking, hallucinations, hostility, confusion, amnesia, convulsions, tremors, and sexual dysfunction.
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The FDA estimates that only 1 percent of
all adverse events are reported to MedWatch, which suggests that roughly 4 million Americans during that nine-year period had a bad or even fatal reaction to Prozac.
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Obviously, the record chalked up by fluoxetine in the clinical trials was not one that would support a successful launch in the marketplace. The public was not likely to embrace a medication that German’s licensing authority, in its initial review, had deemed “totally unsuitable” as a treatment for depression. If Prozac was going to be successful, the psychiatrists that Eli Lilly had paid to run the trials needed to tell a very different story in the medical journals and to the public.