<\/p>\n
Gary Greenberg<\/strong> It\u2019s been just over twenty-five years since Prozac came to market, and more than twenty per cent of Americans now regularly take mind-altering drugs prescribed by their doctors. Almost as familiar as brands like Zoloft and Lexapro is the worry about what it means that the daily routine in many households, for parents and children alike, includes a dose of medications that are poorly understood and whose long-term effects on the body are unknown. Despite our ambivalence,\u00a0sales of psychiatric drugs<\/a>\u00a0amounted to more than seventy billion dollars in 2010. They have become yet another commodity that consumers have learned to live with or even enjoy, like S.U.V.s or Cheetos.<\/p>\n Yet the psychiatric-drug industry is in trouble. \u201cWe are facing a crisis,\u201d the Cornell psychiatrist and New York\u00a0Times<\/i>\u00a0contributor Richard Friedman\u00a0warned last week<\/a>. In the past few years, one pharmaceutical giant after another\u2013GlaxoSmithKline, AstraZeneca, Novartis, Pfizer, Merck, Sanofi\u2013has shrunk or shuttered its neuroscience research facilities. Clinical trials have been halted, lines of research abandoned, and the new drug pipeline has been allowed to run dry.<\/p>\n Why would an industry beat a hasty retreat from a market that continues to boom? (Recent surveys<\/a>\u00a0indicate that mental illness is the leading cause of impairment and disability worldwide.) The answer lies in the history of psychopharmacology, which is more deeply indebted to serendipity than most branches of medicine\u2013in particular, to a remarkable series of accidental discoveries made in the fifteen or so years following the end of the Second World War.<\/p>\n In 1949, John Cade published\u00a0an article<\/a>\u00a0in the\u00a0Medical Journal of Australia<\/i>\u00a0describing his discovery that lithium sedated people who experienced mania. Cade had been testing his theory that manic people were suffering from an excess of uric acid by injecting patients\u2019 urine into guinea pigs, who subsequently died. When Cade diluted the uric acid by adding lithium, the guinea pigs fared better; when he injected them with lithium alone, they became sedated. He noticed the same effect when he tested lithium on himself, and then on his patients. Nearly twenty years after he first recommended lithium to treat manic depression, it became the standard treatment for the disorder.<\/p>\n In the nineteen-forties and fifties, schizophrenic patients in some asylums were treated with cold-induced \u201chibernation\u201d\u2013a state from which they often emerged lucid and calm. In one French hospital, the protocol also called for chlorpromazine, a new drug thought to increase the hibernation effect. One day, some nurses ran out of ice and administered the drug on its own. When it calmed the patients, chlorpromazine, later named Thorazine, was\u00a0recognized in 1952<\/a>\u00a0as the first drug treatment for schizophrenia\u2013a development that encouraged doctors to believe that they could use drugs to manage patients outside the asylum, and thus shutter their institutions.<\/p>\n In 1956, the Swiss firm Geigy wanted in on the antipsychotics market, and it asked a researcher and asylum doctor, Roland Kuhn, to test out a drug that, like Thorazine, was an antihistamine\u2013and thus was expected to have a sedating effect. The results were not what Kuhn desired: when the schizophrenic patients took the drug, imipramine, they became more agitated, and one of them, according to a member of the research team, \u201crode, in his nightshirt, to a nearby village, singing lustily.\u201d He added, \u201cThis was not really a very good PR exercise for the hospital.\u201d But it was the inspiration for Kuhn and his team to reason that \u201cif the flat mood of schizophrenia could be lifted by the drug, then could not a depressed mood be elevated also?\u201d Under the brand name Tofranil, imipramine went on to become the first antidepressant\u2013and one of the first blockbuster psychiatric drugs.<\/p>\n American researchers were also interested in antihistamines. In 1957, Leo Sternbach, a chemist for Hoffmann-La Roche who had spent his career researching them, was about to throw away the last of a series of compounds he had been testing that had proven to be pharmacologically inert. But in the interest of completeness, he was convinced to test the last sample. \u201cWe thought the expected negative pharmacological results would cap our work on this series of compounds,\u201d one of his colleagues later recounted. But the drug turned out to have muscle-relaxing and sedative properties. Instead of becoming the last in a list of failures, it became the first in a series of spectacular successes\u2013the benzodiazepenes, of which Sternbach\u2019s Librium and Valium were the flagships.<\/p>\n By 1960, the major classes of psychiatric drugs\u2013among them, mood stabilizers, antipsychotics, antidepressants, and anti-anxiety drugs, known as anxiolytics\u2013had been discovered and were on their way to becoming a seventy-billion-dollar market. Having been discovered by accident, however, they lacked one important element: a theory that accounted for why they worked (or, in many cases, did not).<\/p>\n That didn\u2019t stop drug makers and doctors from claiming that they knew. Drawing on another mostly serendipitous discovery of the fifties\u2013that the brain did not conduct its business by sending sparks from neuron to neuron, as scientists previously thought, but rather by sending chemical messengers across synapses\u2013they fashioned an explanation: mental illness was the result of imbalances among these neurotransmitters, which the drugs treated in the same way that insulin treats diabetes.<\/p>\n The appeal of this account is obvious: it combines ancient notions of illness (specifically, the idea that sickness resulted from imbalanced humors) with the modern understanding of the molecular culprits that make us suffer\u2013germs. It held out the hope that mental illness could be treated in the same way as pneumonia or hypertension: with a single pill. Drug companies wasted no time in promulgating it. Merck, the manufacturer of Elavil, commissioned the psychiatrist Frank Ayd to write a book called\u00a0Recognizing the Depressed Patient<\/i>, in which he extolled the \u201cchemical revolution in psychiatry\u201d and urged doctors to reassure patients they weren\u2019t losing their minds, but rather suffering a \u201ccommon illness\u201d with a \u201cphysical basis\u201d and a pharmacological cure. Merck sent Ayd\u2019s book to fifty thousand doctors around the country. In 1965, Joseph Schildkraut, a psychiatrist at the National Institute of Mental Health, reverse-engineered antidepressants and offered an actual theory: at least when it came to depression, the imbalances were to be found in the neurotransmitters he thought were affected by the drugs, dopamine and norepinephrine. Seven years after antidepressants were invented, and five years after Ayd asserted that depression was a chemical problem, psychiatrists finally had a precise, scientific explanation for why they worked. The paper quickly became one of the most cited articles in the medical literature.<\/p>\n But Schildkraut was wrong. Within a few years, as technology expanded our ability to peer into the brain, it became clear that antidepressants act mostly by increasing the availability of the neurotransmitter serotonin\u2013rather than dopamine and norepinephrine, as previously thought. A new generation of antidepressants\u2013the selective serotonin reuptake inhibitors (S.S.R.I.s), including Prozac, Zoloft, and Paxil\u2013was developed to target it. The ability to claim that the drugs targeted a specific chemical imbalance was a marketing boon as well, assuring consumers that the drugs had a scientific basis. By the mid-nineties, antidepressants were the best-selling class of prescription medications in the country. Psychiatry appeared to have found magic bullets of its own.<\/p>\n The serotonin-imbalance theory, however, has turned out to be just as inaccurate as Schildkraut\u2019s. While S.S.R.I.s surely alter serotonin metabolism, those changes do not explain why the drugs work, nor do they explain why\u00a0they have proven to be no more effective<\/a>\u00a0than placebos in clinical trials. Within a decade of Prozac\u2019s approval by the F.D.A. in 1987, scientists had concluded that serotonin was only a finger pointing at one\u2019s mood\u2013that the causes of depression and the effects of the drugs were far more complex than the chemical-imbalance theory implied. The ensuing research has mostly yielded more evidence that the brain, which has more neurons than the Milky Way has stars and is perhaps one of the most complex objects in the universe, is an elusive target for drugs.<\/p>\n Despite their continued failure to understand how psychiatric drugs work, doctors continue to tell patients that their troubles are the result of chemical imbalances in their brains. As Frank Ayd pointed out, this explanation helps reassure patients even as it encourages them to take their medicine, and it fits in perfectly with our expectation that doctors will seek out and destroy the chemical villains responsible for all of our suffering, both physical and mental. The theory may not work as science, but it is a devastatingly effective myth.<\/p>\n Whether or not truthiness, as one might call it, is good medicine remains to be seen. No one knows\u00a0how important placebo effects are to successful treatment<\/a>, or how exactly to implement them, a topic Michael Specter wrote about in the magazine in 2011. But the dry pipeline of new drugs bemoaned by Friedman is an indication that the drug industry has begun to lose faith in the myth it did so much to create. As Steven Hyman, the former head of the National Institute of Mental Health,\u00a0wrote last year<\/a>, the notion that \u201cdisease mechanisms could \u2026 be inferred from drug action\u201d has succeeded mostly in \u201ccapturing the imagination of researchers\u201d and has become \u201csomething of a scientific curse.\u201d Bedazzled by the prospect of unraveling the mysteries of psychic suffering, researchers have spent recent decades on a fool\u2019s errand\u2013chasing down chemical imbalances that don\u2019t exist. And the result, as Friedman put it, is that \u201cit is hard to think of a single truly novel psychotropic drug that has emerged in the last thirty years.\u201d<\/p>\n Despite the\u00a0BRAIN<\/small>\u00a0initiative recently announced<\/a>\u00a0by the Obama Administration, and the N.I.M.H.\u2019s renewed efforts to stimulate research on the neurocircuitry of mental disorder, there is nothing on the horizon with which to replace the old story. Without a new explanatory framework, drug-company scientists don\u2019t even know where to begin, so it makes no sense for the industry to stay in the psychiatric-drug business. And if loyalists like Hyman and Friedman continue to say out loud what they have been saying to each other for many years\u2013that, as Friedman told\u00a0Times<\/i>\u00a0readers, \u201cjust because an S.S.R.I. antidepressant increases serotonin in the brain and improves mood, that does not mean that serotonin deficiency is the cause of the disease\u201d\u2013then consumers might also lose faith in the myth of the chemical imbalance.<\/p>\n Gary Greenberg<\/a>\u00a0is a practicing psychotherapist and the author of \u201cThe Book of Woe: The DSM and the Unmaking of Psychiatry<\/a>.\u201d<\/em><\/p>\n Correction: Due to an editing error, the antidepressant Tofranil was originally identified as Elavil.<\/em><\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":" Gary Greenberg The New Yorker Sept. 4, 2013 It\u2019s been just over twenty-five years since Prozac came to market, and more than twenty per cent of Americans now regularly take mind-altering drugs prescribed by their doctors. Almost as familiar as brands like Zoloft and Lexapro is the worry about what it means that the daily […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[487],"tags":[],"class_list":{"0":"post-65557","1":"post","2":"type-post","3":"status-publish","4":"format-standard","6":"category-breaking-news"},"_links":{"self":[{"href":"http:\/\/rinf.com\/alt-news\/wp-json\/wp\/v2\/posts\/65557","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/rinf.com\/alt-news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/rinf.com\/alt-news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/rinf.com\/alt-news\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/rinf.com\/alt-news\/wp-json\/wp\/v2\/comments?post=65557"}],"version-history":[{"count":0,"href":"http:\/\/rinf.com\/alt-news\/wp-json\/wp\/v2\/posts\/65557\/revisions"}],"wp:attachment":[{"href":"http:\/\/rinf.com\/alt-news\/wp-json\/wp\/v2\/media?parent=65557"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/rinf.com\/alt-news\/wp-json\/wp\/v2\/categories?post=65557"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/rinf.com\/alt-news\/wp-json\/wp\/v2\/tags?post=65557"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
\nThe New Yorker<\/a>
\nSept. 4, 2013<\/p>\n