My Age of Anxiety: Fear, Hope, Dread, and the Search for Peace of Mind

by Scott Stossel

  But even drugged to the gills, I remained filled with dread about the impending book tour, so I went also to a young but highly regarded Stanford-trained psychologist who specialized in cognitive behavioral therapy, or CBT. “First thing we’ve got to do,” she said in one of my early sessions with her, “is to get you off these drugs.” A few sessions later, she offered to take my Xanax from me and lock it in a drawer in her desk. She opened the drawer to show me the bottles deposited there by some of her other patients, holding one up and shaking it for effect. The drugs, she said, were a crutch that prevented me from truly experiencing and thereby confronting my anxiety; if I didn’t expose myself to the raw experience of anxiety, I would never learn that I could cope with it on my own.

  She was right, I knew. Exposure therapy is based on fully experiencing your anxiety, which is hard to do if you’re taking antianxiety medications. But with the book tour looming, my fear was that I might not, in fact, be able to cope with it.

  I went back to the Harvard psychopharmacologist (let’s call him Dr. Harvard) and described the course of action the Stanford psychologist (let’s call her Dr. Stanford) had proposed. “It’s your call,” he said. “You could try giving up the medication. But your anxiety is clearly so deeply rooted in your biology that even mild stress provokes it. Only medication can control your biological reaction. And it may well be that your anxiety is so acute that the only way you’ll be able to get to the point where any kind of behavioral therapy can begin to be effective is by taking the edge off your physical symptoms with drugs.”

  “What if I get addicted to Xanax and have to be on it all my life?” I asked. Benzodiazepines are notorious for inducing dependency. Withdrawing too suddenly from them can produce horrific side effects.

  “So what if you do?” he said. “I have a patient coming in this afternoon who’s been taking it for twenty years. She couldn’t live without it.”

  At my next session with Dr. Stanford, I told her I was afraid to give up my Xanax and related what Dr. Harvard had said to me. She looked betrayed. I thought for a moment that she might cry. After that, I stopped telling her about my visits to Dr. Harvard. My continued consultations with him felt illicit.

  Dr. Stanford was more likable, and more pleasant to talk to, than Dr. Harvard; she tried to understand what caused my anxiety and seemed to care about me as an individual personality. Dr. Harvard, on the other hand, seemed to see me as a type—an anxiety patient—to be treated with a one-size-fits-all solution: drugs. One day I read in the newspaper that he was treating a depressed gorilla at the local zoo. Dr. Harvard’s treatment of choice for the gorilla in question? Celexa, the same SSRI he was prescribing for me.

  I can’t say for certain whether the drug worked for the gorilla. Reportedly, it did. But could there be a more potent demonstration that Dr. Harvard’s approach to treatment was resolutely biological? For him, the content of any psychic distress—and certainly the meaning of it—mattered less than the fact of it: such distress, whether in a human or some other primate, was a medical-biological malfunction that could be fixed with drugs.

  What to do? Dr. Harvard was telling me that I, like the gorilla, had a medical problem in need of pharmaceutical intervention. Dr. Stanford was telling me that my problem was not principally biological but rather cognitive: if I could simply correct dysfunctions in how I thought (through force of will and cognitive retraining and direct exposure to my greatest fears), then my anxiety would be reduced. But the drugs I was on, Dr. Stanford said, were impeding my ability to address those dysfunctions in an effective way.*

  I kept trying to give up my Klonopin and Xanax in order to do proper cognitive retraining, and I would sometimes even succeed at this in small ways—only to be overwhelmed with anxiety again and resort to fumbling miserably through my pockets for the Xanax. As much as I would have liked to have cured myself through fixing my thinking, or achieving spiritual peace, or simply learning to cope, I seemed always to be ending up like the depressed gorilla, in need of artificial adjustments to my neurotransmitters to fix my anxious, broken brain.

  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. By doing this, they are adding to happiness, human achievement, and the dignity of man.

  —FRANK BERGER, “ANXIETY AND THE DISCOVERY OF TRANQUILIZERS,” IN Discoveries in Biological Psychiatry (1970)

  To what extent would Western culture be altered by widespread use of tranquilizers? Would Yankee initiative disappear? Is the chemical deadening of anxiety harmful?

  —STANLEY YOLLES, DIRECTOR OF THE NATIONAL INSTITUTE OF MENTAL HEALTH, IN TESTIMONY GIVEN TO THE U.S. SENATE SELECT COMMITTEE ON SMALL BUSINESS, MAY 1967

  Sigmund Freud, the father of psychoanalysis, relied heavily on drugs in managing his anxiety. Six of his earliest scientific papers were on the benefits of cocaine, which he used regularly for at least a decade beginning in the 1880s. “In my last serious depression I took cocaine again,” he wrote to his wife in 1884, “and a small dose lifted me to the heights in a wonderful fashion. I am just now collecting the literature for a song of praise to this magical substance.” He believed his research on the drug’s medicinal properties would make him famous. Deeming the drug to be no more addictive than coffee, he prescribed it, to himself and to others, as a treatment for everything from nervous tension and melancholy to indigestion and morphine addiction. Freud called cocaine a “magic drug”: “I take very small doses of it regularly against depression and against indigestion, and with the most brilliant success.” He also took it to alleviate his social anxiety before the evening salons he attended at the Paris home of his mentor Jean-Martin Charcot.† Only after he prescribed cocaine to a close friend who went on to become fatally addicted did Freud’s enthusiasm for the drug wane. But by then Freud’s own experience with cocaine had solidified his conviction that some mental illnesses have a physical basis in the brain. It is an irony of medical history that even as Freud’s later work would make him the progenitor of modern psychodynamic psychotherapy, which is generally premised on the idea that mental illness arises from unconscious psychological conflicts, his papers on cocaine make him one of the fathers of biological psychiatry, which is governed by the notion that mental distress is partly caused by a physical or chemical malfunction that can be treated with drugs.

  Much of the history of modern psychopharmacology has the same ad hoc quality as Freud’s experimentation with cocaine. Every one of the most commercially significant classes of antianxiety and antidepressant drugs of the last sixty years was discovered by accident or was originally developed for something completely unrelated to anxiety or depression: to treat tuberculosis, surgical shock, allergies; to use as an insecticide, a penicillin preservative, an industrial dye, a disinfectant, rocket fuel.

  Yet despite its haphazardness, the recent history of psychopharmacology has shaped our modern understanding of mental illness. Recall that neither “anxiety” nor “depression”—two terms that today have become part of both the medical and the popular lexicon—existed as clinical categories half a century ago. Before the 1920s, no one had ever been diagnosed with depression; before the 1950s, hardly anyone was diagnosed with straightforward anxiety.

  So what changed? One answer is that pharmaceutical companies in effect created these categories. What began as targets for marketing campaigns eventually became reified as diseases.

  By this I do not mean to suggest that before the 1950s people were not “anxious” or “depressed” in the senses we understand those words today. Some people, some percentage of the time, have always felt pathologically unhappy and afraid. This was the case for millennia before the terms “anxiety” and “depression” were popularized to describe emotional states or clinical disorders. (“The tears of the world are a constant quantity,” as Samuel Beckett put it.) But not until the middle of the last century, when new drugs geared toward mitigating these emotional state
s were concocted, did these states get delimited as the “diseases” we understand them to be today.

  Before 1906, when the fledgling Food and Drug Administration started requiring drugmakers to list their products’ ingredients, consumers didn’t realize that in taking some of the most popular antianxiety remedies of the time—such as Neurosine or Dr. Miles’s Nervine (advertised as “the scientific remedy for nervous disorders”) or Wheller’s Nerve Vitalizers or Rexall’s Americanitis Elixir—they were ingesting alcohol or marijuana or opium.‡ In 1897, the German drug company Bayer began marketing diacetylmorphine, a compound that had been widely used on the battlefields of the American Civil War and the Franco-Prussian War, as a painkiller and cough suppressant. This new medication—under the trade name Heroin—was available in American pharmacies without a prescription until 1914.§ The 1899 edition of The Merck Manual, then as now a respected compendium of the most up-to-date medical information, recommended opium as a standard treatment for anxiety.

  The serene confidence with which The Merck Manual—as well as the physicians and apothecaries of the time—glibly dispensed recommendations for drugs we now know to be addictive, unhealthy, or useless raises the question of whether we should place much trust in the similarly serene confidence of the physicians and drug manuals of today. Yes, today’s researchers and clinicians are armed with data from controlled studies and findings from neuroimaging and blood assays, and they are buttressed—or held back, depending on your perspective—by a more cautious FDA that demands years’ worth of animal testing and clinical trials before a drug can be approved for sale. But a hundred years from now, medical historians may once again be marveling at the addictive, toxic, or useless substances we consume in such great quantities today.

  For the first half of the twentieth century, barbiturates were the most popular remedy for strained nerves. Originally synthesized in 1864 by a German chemist who combined condensed urea (found in animal waste) with diethyl malonate (which derives from the acid in apples), barbituric acid seemed, at first, to have no productive use. But in 1903, when researchers at Bayer gave barbituric acid to dogs, the dogs fell asleep. Within months, Bayer was marketing barbital, the first commercially available barbiturate, to consumers. (Bayer named the drug Veronal because one of its scientists believed Verona, Italy, to be the most peaceful city on earth.) In 1911, the company released a longer-acting barbiturate, phenobarbital, under the trade name Luminal, which would go on to become the most popular drug in the category. By the 1930s, barbiturates had almost completely displaced their late nineteenth-century predecessors—chloral hydrate and bromides, as well as opium—as the treatment of choice for “nerve troubles.”‖

  As early as 1906, so many Americans were taking, and sometimes overdosing on, Veronal that The New York Times editorialized against the overprescription of such “quick-cure nostrums,” but to little effect: in the 1930s, The Merck Manual was still recommending Veronal for the treatment of “extreme nervousness, neurasthenia, hypochondria, melancholia,” and other “conditions of anxiety.” Veronal and Luminal—advertised as “aspirin for the mind”—dominated what would today be called the anxiety medication market for decades. By 1947, there were thirty different barbiturates being sold under separate trade names in the United States; the three most popular were Amytal (amobarbital), Nembutal (pentobarbital), and Seconal (secobarbital). Since “anxiety” and “depression” didn’t officially exist yet, the barbiturates tended to be prescribed for “nerves” (or “nerve troubles”), “tension,” and insomnia.

  But the barbiturates had two big drawbacks: they were highly addictive, and accidental overdoses were common and often lethal. In 1950, at least a thousand Americans fatally overdosed on barbiturates. (My great-grandmother and Marilyn Monroe, among many others, would go on to do so in the 1960s.) In 1951, The New York Times called barbiturates “more of a menace to society than heroin or morphine” and declared that “the matron who regards a pink pill as much of a bedtime necessity as brushing her teeth, the tense business man who gulps a white capsule to ease his nerves before an important conference, the college student who swallows a yellow ‘goof ball’ to breeze through an examination, and the actor who takes a ‘blue angel’ to bolster his self-confidence are aware that excessive use of barbiturates is ‘not good for the system,’ but are ignorant of the extent of the hazard.”

  You would think that such heavy consumption of barbiturates would have made drug companies keen to develop new and better nostrums. But when Frank Berger, a research scientist at the Wallace Laboratories subsidiary of Carter Products, tried to interest company executives in a new antianxiety medication he had synthesized in the late 1940s, they showed no interest. For one thing, they argued, therapy for anxiety was supposed to focus on psychological issues or unresolved personal problems, not on biology or chemistry—a distinction that from the vantage point of modern biological psychiatry seems quaint. Besides, psychoactive drugs lay outside Carter’s usual commercial domain, which consisted of such things as laxatives (Carter’s Little Liver Pills), deodorant (Arrid), and depilatory cream (Nair).

  Berger had stumbled on the antianxiety properties of this new substance entirely by accident. Born in what is now the Czech Republic in 1913, Berger had, after earning his medical degree at the University of Prague, conducted immunology research that established him as a promising scientist. But when Hitler annexed Austria and seemed poised to claim Czechoslovakia, Berger, who was Jewish, escaped to London.

  Unable to find work there, Berger and his wife became homeless, sleeping on park benches and eating at soup kitchens. Eventually, Berger got a job as a doctor in a refugee camp, where he learned English, and then moved on to a job as an antibiotics researcher at the Public Health Laboratory near Leeds.

  By 1941, penicillin had been demonstrated to be an effective treatment for bacterial infections. But manufacturing and preserving penicillin in quantities large enough to be useful in fighting infections among Allied soldiers proved vexing. “The mold is as temperamental as an opera singer,” lamented one pharmaceutical executive. So Berger, along with hundreds of other scientists, went to work trying to find better extraction and purification techniques for the revolutionary antibiotic. He was particularly successful in developing a method for preserving the mold long enough to distribute it more widely. After his research was published in prestigious scientific journals, a British drug company offered the once-homeless chemist a high-ranking position.

  One of the penicillin preservatives Berger tested was a compound called mephenesin, which he had synthesized by modifying a commercially available disinfectant. When he injected mice with mephenesin to test its toxicity, Berger observed something he’d never seen before: “The compound had a quieting effect on the demeanor of the animals.”

  Berger had, quite by accident, discovered the first of a revolutionary new class of drugs. When mephenesin was found to have a similar sedating effect on humans, the Squibb Corporation, recognizing a commercial opportunity, began distributing mephenesin as a drug to induce relaxation before surgery. Sold under the trade name Tolserol, mephenesin had by 1949 become one of Squibb’s most prescribed drugs.

  But mephenesin wasn’t very potent in pill form, and its effects were short-lived. Berger resolved to develop a more powerful version. In the summer of 1949, he took a job as the president and medical director of Carter’s Wallace Labs subsidiary in New Brunswick, New Jersey. There, Berger and his team set to work synthesizing and testing compounds that might prove more potent than mephenesin. Eventually, they identified a dozen (out of the roughly five hundred they synthesized) that seemed promising; after more experiments on animals, they narrowed the list down to four and then to one, called meprobamate, which they patented in July 1950. Berger’s team found that meprobamate relaxed mice. The effect on monkeys was even more vivid. “We had about twenty Rhesus and Java monkeys,” Berger would later tell the medical historian Andrea Tone. “They’re vicious, and you’ve got to wear t
hick gloves and a face guard when you handle them.” But after they were injected with meprobamate, they became “very nice monkeys—friendly and alert.” Further testing revealed meprobamate to be longer lasting than mephenesin and less toxic than barbiturates.

  Meanwhile, two new papers in top medical journals were providing the first reports of the therapeutic effects of mephenesin—which, remember, was less potent than meprobamate. One of the studies, conducted by doctors at the University of Oregon, found that when mephenesin was given to 124 patients who had sought treatment from their physicians for “anxiety tension states,” more than half experienced a significant reduction in anxiety—to the point where they resembled, in the words of the researchers, “individuals who are pleasantly and comfortably at ease.” Other reports from mental hospitals showed similar results. Soon the first small-scale studies of meprobamate were finding the same thing: the drug significantly reduced what doctors of the time tended to call “tension.”