Anatomy of an Epidemic (19 page)

Sigmund Freud provided psychiatry with a rationale for treating this group of patients and, in so doing, enabled psychiatry to move out of the asylum and into the office. Born in 1856, Freud set out his shingle as a nerve doctor in Vienna in 1886, which meant that many of his patients were women suffering from neurasthenia (Beard’s disease had become popular in Europe, too). After hours of conversation with his clients, Freud became convinced that their feelings of dread and worry were psychological in origin, rather than the result of tired nerves. In 1895, he wrote about “anxiety neurosis” in women, which he theorized arose in large part from their unconscious repression of sexual desires and fantasies. Those suffering from such psychological conflicts could find relief through psychoanalysis, the patient on the couch led by the doctor into an exploration of her unconscious mind.

At this time, psychiatry was a profession for those who treated mad patients in the asylum. People with tired nerves went to see a
nerve doctor or a general practitioner for help. But if anxiety arose from a psychological disorder in the brain, rather than from a frazzling of the nerves, then it made sense that psychiatrists could tend to these patients, and after Freud visited America in 1909, psychoanalytic societies began to form, with New York City the hub of this new therapy. Nationwide, only 3 percent of psychiatrists were in private practice in 1909; thirty years later, 38 percent were seeing patients in private settings.
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Moreover, Freudian theory made nearly everyone a candidate for the psychiatrist’s couch. “Neurotics,” Freud explained during his 1909 tour, “fall ill of the same complexes with which we sound people struggle.”
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Thanks to Freudian theories, psychiatric disorders were now divided into two basic categories: psychotic and neurotic. In 1952, the American Psychiatric Association published the first edition of its
Diagnostic and Statistical Manual
, and it described the neurotic patient in this way:

Such was the understanding of anxiety when Miltown came to market. Anxious people had their feet firmly planted in reality, and rarely was anxiety a condition that required hospitalization. In 1955, there were only 5,415 “psychoneurotic” patients in state mental hospitals.
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As Stanford psychiatrist Leo Hollister confessed after the benzodiazepines were introduced, these drugs were “designed to treat what many would regard as a ‘minor disorder.’”
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The drugs were a balm for the “walking wounded,” and thus, as we review the outcomes literature for the benzodiazepines, we should expect this patient group to function well. After all, that was the future promised by Miltown inventor Frank Berger: “Tranquilizers,
by attenuating the disruptive influence of anxiety on the mind, open the way to a better and more coordinated use of the existing gifts,” he said.
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When Miltown first appeared, there were a number of studies published in medical journals that told—as two Harvard Medical School researchers, David Greenblatt and Richard Shader, later re-called—of how it “was almost magically effective in reducing anxiety.” But as has often been the case in psychiatry, once a successor pill appeared on the market (Librium, in 1960), the efficacy of the old drug suddenly began to fade. In their review of the Miltown literature in 1974, Greenblatt and Shader found that in twenty-six well-controlled trials, there were only five in which Miltown “was more effective than placebo” as a treatment for anxiety. Nor was there any evidence that Miltown was better than a barbiturate in calming the nerves. The initial popularity of this drug, they wrote, “illustrates how factors other than scientific evidence may determine physicians’ patterns of drug use.”
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However, Miltown’s fall from favor with the public arose from a different problem than lack of scientific efficacy. Many who tried the drug found that they became sick when they stopped taking it, and in 1964, Carl Essig, a scientist at the Addiction Research Center in Lexington, Kentucky, reported that it “could induce physical dependence in man.”
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Science News
quickly announced that the happy pill could be “addictive,” and on April 30, 1965,
Time
all but buried Miltown. There is “a growing disillusionment with Miltown on the part of many doctors,” the magazine wrote. “Some doubt that it has any more tranquilizing effect than a dummy sugar pill…. A few physicians have reported that in some patients, Miltown may cause a true addiction, followed by withdrawal symptoms like those of narcotics users ‘kicking the habit.’”
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Publicly, the benzodiazepines mostly escaped this opprobrium during the 1960s. When Hoffmann-La Roche brought Librium to
market in 1960, it claimed that its drug provided “pure anxiety relief,” and unlike Miltown and the barbiturates, was “safe, harmless and non-addicting.” That belief took hold and the FDA did little to counter it, even though very early on it started receiving letters from people who were experiencing odd and quite distressing symptoms when they tried to quit a benzodiazepine. They told of awful insomnia, anxiety more severe than they had known before, and a rash of physical symptoms—tremors, headaches, and nerves that “jangled like crazy.” As one man wrote the FDA, “I was not sleeping and in general felt horrible. Sometimes I thought I would die and other times wished I had.”
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Although the FDA held a hearing on the matter, it did not impose any legal control on benzodiazepines similar to what had been placed on amphetamines and barbiturates, and so the public’s belief that the drugs were relatively nonaddictive and harmless survived until 1975, when the U.S. Justice Department demanded that they be classified as schedule IV drugs under the Controlled Substances Act. This designation limited the number of refills a patient could obtain without a new prescription, and revealed to the public that the government had concluded that benzodiazepines were, in fact, addictive.

“Danger ahead! Valium—The Pill You Love Can Turn on You,” a
Vogue
headline screamed. A benzodiazepine, the magazine explained, could lead to a “far worse addiction than heroin.”
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The Valium backlash had begun, particularly in the pages of women’s magazines, and soon
Ms
. magazine provided readers with firstperson accounts of the horrors of withdrawing from it. “My withdrawal symptoms are a double-dose of the anxiety, irritableness, and insomnia I used to feel,” one user said. Confessed another: “I can’t begin to describe the physical and mental anguish that accompanied my withdrawal.”
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The happiness pill of the 1950s was turning into the misery pill of the 1970s, with the
New York Times
reporting in 1976 that “some critics go so far to say that [Valium] is doing more harm than good, or even deny that it is doing any good at all for the great majority of patients. Some cry with alarm that it is far from being as safe as it is proclaimed, that it can be hideously and dangerously addictive, and may be the direct cause of addicts’ deaths.”
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Two million Americans were said to be addicted to
benzodiazepines, four times the number of heroin addicts in the country, and one of the pill takers turned out to be former first lady Betty Ford, who checked herself into an alcohol and drug rehab center in 1978. Abuse of tranquilizers, said her physician Joseph Pursch, was “the nation’s number one health problem.”
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Over the next few years, the benzodiazepines officially fell from grace. In 1979, Senator Edward Kennedy held a Senate Health Subcommittee hearing on the dangers of benzodiazepines, which he said had “produced a nightmare of dependence and addiction, both very difficult to treat and recover from.”
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After reviewing the scientific literature, the White House Office of Drug Policy and the National Institute of Drug Abuse concluded that the drugs’ sleep-promoting effects didn’t last more than two weeks, and this finding was soon seconded by the Committee on the Review of Medicines in the United Kingdom, which found that the drugs’ anti-anxiety effects didn’t last beyond four months. As such, the committee recommended that “patients receiving benzodiazepine therapy be carefully selected and monitored and that prescriptions be limited to short-term use.”
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As an editorial in the
British Medical Journal
put it: “Now that benzodiazepines have been shown to cause drug dependence should their use be more closely controlled—or even banned?”
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This story of the benzodiazepines’ fall from grace might seem like ancient history, a footnote in our quest to understand why there has been such a rise in the number of disabled mentally ill in the United States over the past fifty years, except for the fact that the benzodiazepines never really went away. Although the number of prescriptions for benzodiazepines dropped after they were classified as schedule IV drugs, from 103 million in 1975 to 71 million in 1980, the following year Upjohn brought Xanax to market, and this helped stabilize sales of benzodiazepines.
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Psychiatrists continued to prescribe benzodiazepines to many of their nervous patients, and in 2002, Stephen Stahl, a well-known psychopharmacologist at the
University of California in San Diego, confessed to psychiatry’s dirty little secret in an article titled “Don’t Ask, Don’t Tell, But Benzodiazepines Are Still the Leading Treatments for Anxiety Disorders.”
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Since that time, the prescribing of benzodiazepines in the United States has increased, from 69 million prescriptions in 2002 to 83 million in 2007, which isn’t all that far below the number written at the height of the Valium craze in 1973.
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So, given that benzodiazepines have been widely used for fifty years, we need to look at what science has to tell about these drugs, and whether their use may be contributing in some way to the increase in the number of disabled mentally ill in the United States.

As anyone who has taken a benzodiazepine can attest, it acts rapidly, and if a person hasn’t become habituated to the drug, it will numb his or her emotional distress. As such, a benzodiazepine has an obvious utility in helping people through a situational crisis. The writer Andrea Tone, in her book
The Age of Anxiety
, relates how a benzodiazepine enabled her to get on an airplane after she somewhat mysteriously developed a fear of flying. But as clinical trials revealed, that immediate efficacy quickly begins to fade and pretty much disappears by the end of four to six weeks.

In 1978, Kenneth Solomon at Albany Medical College in New York reviewed seventy-eight double-blind trials of benzodiazepines and determined that the drugs had proved to be significantly better than a placebo in only forty-four of them. At best, the collective results could be said to “hint at therapeutic efficacy,” he wrote.
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Five years later, Arthur Shapiro at Mt. Sinai School of Medicine in New York City fleshed out this efficacy picture a bit more, reporting that in a trial of 224 anxious patients, Valium proved superior to a placebo for the first week, but then this advantage began to lessen. Based on the patients’ self-assessment of their symptoms, by the end of the second week there was no difference between the drug and a placebo, and by the end of six weeks, the placebo group was faring slightly better. “It is unlikely in our opinion that carefully controlled
studies would consistently show significant benzodiazepine therapeutic antianxiety effects,” Shapiro wrote.
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That picture of the short-term efficacy of benzodiazepines has not markedly changed since then. The drugs show clear efficacy for the first week, and then their advantage over a placebo abates. But, as British investigators noted in 1991, this brief period of efficacy comes at a fairly high cost. “Both psychomotor and cognitive functioning may be impaired, and amnesia is a common effect of all benzodiazepines,” they said.
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In 2007, researchers in Spain looked at whether these adverse events negated the small “efficacy benefit” provided by the drugs, and found that the drop-out rates in clinical trials, a measure often used to assess the overall “effectiveness” of a drug, were the same for benzodiazepine and placebo patients. “This systematic review did not find convincing evidence of the short-term effectiveness of the benzodiazepines in the treatment of generalized anxiety disorder,” they reported.
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Malcolm Lader, a psychiatrist at the Institute of Psychiatry in London who is one of the world’s leading experts on benzodiazepines, explained the importance of this finding in an interview: “Effectiveness is a measure of what it’s like in real practice.”
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Although the first report of benzodiazepine dependence appeared in the scientific literature in 1961, when Leo Hollister at Stanford University reported that patients withdrawing from Librium were experiencing odd symptoms, it wasn’t until the Justice Department classified benzodiazepines as schedule IV drugs that researchers began investigating the problem with any vigor. In 1976, physicians Barry Maletzky and James Kotter jump-started this inquiry, reporting that when their patients stopped taking Valium, many complained of “extreme anxiety.”
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Two years later, physicians at Pennsylvania State University announced that patients withdrawing from benzodiazepines often experienced “an increase in anxiety above baseline levels … a condition that we term ‘rebound anxiety.’”
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In Britain, Lader reported similar findings. “Anxiety rose sharply during withdrawal, and to a point of panic in several patients. Patients commonly experienced bodily symptoms of anxiety, such as a choking feeling, dry mouth, hot and cold, legs like jelly, etc.”
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