You arrive for work and someone informs you that you have until five o’clock to clean out your office. You have been laid off. At first, your family is brave and supportive, and although you’re in shock, you convince yourself that you were ready for something new. Then you start waking up at 3 A.M., apparently in order to stare at the ceiling. You can’t stop picturing the face of the employee who was deputized to give you the bad news. He does not look like George Clooney. You have fantasies of terrible things happening to him, to your boss, to George Clooney. You find—a novel recognition—not only that you have no sex drive but that you don’t care. You react irritably when friends advise you to let go and move on. After a week, you have a hard time getting out of bed in the morning. After two weeks, you have a hard time getting out of the house. You go see a doctor. The doctor hears your story and prescribes an antidepressant. Do you take it?
However you go about making this decision, do not read the psychiatric literature. Everything in it, from the science (do the meds really work?) to the metaphysics (is depression really a disease?), will confuse you. There is little agreement about what causes depression and no consensus about what cures it. Virtually no scientist subscribes to the man-in-the-waiting-room theory, which is that depression is caused by a lack of serotonin, but many people report that they feel better when they take drugs that affect serotonin and other brain chemicals.
There is suspicion that the pharmaceutical industry is cooking the studies that prove that antidepressant drugs are safe and effective, and that the industry’s direct-to-consumer advertising is encouraging people to demand pills to cure conditions that are not diseases (like shyness) or to get through ordinary life problems (like being laid off). The Food and Drug Administration has been accused of setting the bar too low for the approval of brand-name drugs. Critics claim that health-care organizations are corrupted by industry largesse, and that conflict-of-interest rules are lax or nonexistent. Within the profession, the manual that prescribes the criteria for official diagnoses, the Diagnostic and Statistical Manual of Mental Disorders, known as the D.S.M., has been under criticism for decades. And doctors prescribe antidepressants for patients who are not suffering from depression. People take antidepressants for eating disorders, panic attacks, premature ejaculation, and alcoholism.
These complaints are not coming just from sociologists, English professors, and other troublemakers; they are being made by people within the field of psychiatry itself. As a branch of medicine, depression seems to be a mess. Business, however, is extremely good. Between 1988, the year after Prozac was approved by the F.D.A., and 2000, adult use of antidepressants almost tripled. By 2005, one out of every ten Americans had a prescription for an antidepressant. IMS Health, a company that gathers data on health care, reports that in the United States in 2008 a hundred and sixty-four million prescriptions were written for antidepressants, and sales totalled $9.6 billion. As a depressed person might ask, What does it all mean?
Two new books, Gary Greenberg’s “Manufacturing Depression” (Simon & Schuster; $27) and Irving Kirsch’s “The Emperor’s New Drugs” (Basic; $23.95), suggest that dissensus prevails even among the dissidents. Both authors are hostile to the current psychotherapeutic regime, but for reasons that are incompatible. Greenberg is a psychologist who has a practice in Connecticut. He is an unusually eloquent writer, and his book offers a grand tour of the history of modern medicine, as well as an up-close look at contemporary practices, including clinical drug trials, cognitive-behavioral therapy, and brain imaging. The National Institute of Mental Health estimates that more than fourteen million Americans suffer from major depression every year, and more than three million suffer from minor depression (whose symptoms are milder but last longer than two years). Greenberg thinks that numbers like these are ridiculous—not because people aren’t depressed but because, in most cases, their depression is not a mental illness. It’s a sane response to a crazy world.
Greenberg basically regards the pathologizing of melancholy and despair, and the invention of pills designed to relieve people of those feelings, as a vast capitalist conspiracy to paste a big smiley face over a world that we have good reason to feel sick about. The aim of the conspiracy is to convince us that it’s all in our heads, or, specifically, in our brains—that our unhappiness is a chemical problem, not an existential one. Greenberg is critical of psychopharmacology, but he is even more critical of cognitive-behavioral therapy, or C.B.T., a form of talk therapy that helps patients build coping strategies, and does not rely on medication. He calls C.B.T. “a method of indoctrination into the pieties of American optimism, an ideology as much as a medical treatment.”
In fact, Greenberg seems to believe that contemporary psychiatry in most of its forms except existential-humanistic talk therapy, which is an actual school of psychotherapy, and which appears to be what he practices, is mainly about getting people to accept current arrangements. And it’s not even that drug companies and the psychiatric establishment have some kind of moral or political stake in these arrangements—that they’re in the game in order to protect the status quo. They just see, in the world’s unhappiness, a chance to make money. They invented a disease so that they could sell the cure.
Greenberg is repeating a common criticism of contemporary psychiatry, which is that the profession is creating ever more expansive criteria for mental illness that end up labelling as sick people who are just different—a phenomenon that has consequences for the insurance system, the justice system, the administration of social welfare, and the cost of health care.
Jerome Wakefield, a professor of social work at New York University, has been calling out the D.S.M. on this issue for a number of years. In “The Loss of Sadness” (2007), Wakefield and Allan Horwitz, a sociologist at Rutgers, argue that the increase in the number of people who are given a diagnosis of depression suggests that what has changed is not the number of people who are clinically depressed but the definition of depression, which has been defined in a way that includes normal sadness. In the case of a patient who exhibits the required number of symptoms, the D.S.M. specifies only one exception to a diagnosis of depression: bereavement. But, Wakefield and Horwitz point out, there are many other life problems for which intense sadness is a natural response—being laid off, for example. There is nothing in the D.S.M. to prevent a physician from labelling someone who is living through one of these problems mentally disordered.
The conversion of stuff that people used to live with into disorders that physicians can treat is not limited to psychiatry, of course. Once, people had heartburn (“I can’t believe I ate the whole thing”) and bought Alka-Seltzer over the counter; now they are given a diagnosis of gastroesophageal reflux disease (“Ask your doctor whether you might be suffering from GERD”) and are written a prescription for Zantac. But people tend to find the medicalization of mood and personality more distressing. It has been claimed, for example, that up to 18.7 per cent of Americans suffer from social-anxiety disorder. In “Shyness” (2007), Christopher Lane, a professor of English at Northwestern, argues that this is a blatant pathologization of a common personality trait for the financial benefit of the psychiatric profession and the pharmaceutical industry. It’s a case of what David Healy, in his invaluable history “The Antidepressant Era” (1997), calls “the pharmacological scalpel”: if a drug (in this case, Paxil) proves to change something in patients (shyness), then that something becomes a disorder to be treated (social anxiety). The discovery of the remedy creates the disease.
Turning shyness into a mental disorder has many downstream consequences. As Steven Hyman, a former director of the National Institute of Mental Health, argues in a recent article, once a diagnosis is ensconced in the manual, it is legitimatized as a subject of scientific research. Centers are established (there is now a Shyness Research Institute, at Indiana University Southeast) and scientists get funding to, for example, find “the gene for shyness”—even though there was never any evidence that the condition has an organic basis. A juggernaut effect is built into the system.
Irving Kirsch is an American psychologist who now works in the United Kingdom. Fifteen years ago, he began conducting meta-analyses of antidepressant drug trials. A meta-analysis is a statistical abstract of many individual drug trials, and the method is controversial. Drug trials are designed for different reasons—some are done to secure government approval for a new drug, and some are done to compare treatments—and they have different processes for everything from selecting participants to measuring outcomes. Adjusting for these differences is complicated, and Kirsch’s early work was roundly criticized on methodological grounds by Donald Klein, of Columbia University, who was one of the key figures in the transformation of psychiatry to a biologically based practice. But, as Kirsch points out, meta-analyses have since become more commonly used and accepted.
Kirsch’s conclusion is that antidepressants are just fancy placebos. Obviously, this is not what the individual tests showed. If they had, then none of the drugs tested would have received approval. Drug trials normally test medications against placebos—sugar pills—which are given to a control group. What a successful test typically shows is a small but statistically significant superiority (that is, greater than could be due to chance) of the drug to the placebo. So how can Kirsch claim that the drugs have zero medicinal value?
His answer is that the statistical edge, when it turns up, is a placebo effect. Drug trials are double-blind: neither the patients (paid volunteers) nor the doctors (also paid) are told which group is getting the drug and which is getting the placebo. But antidepressants have side effects, and sugar pills don’t. Commonly, side effects of antidepressants are tolerable things like nausea, restlessness, dry mouth, and so on. (Uncommonly, there is, for example, hepatitis; but patients who develop hepatitis don’t complete the trial.) This means that a patient who experiences minor side effects can conclude that he is taking the drug, and start to feel better, and a patient who doesn’t experience side effects can conclude that she’s taking the placebo, and feel worse. On Kirsch’s calculation, the placebo effect—you believe that you are taking a pill that will make you feel better; therefore, you feel better—wipes out the statistical difference.
One objection to Kirsch’s argument is that response to antidepressants is extremely variable. It can take several different prescriptions to find a medication that works. Measuring a single antidepressant against a placebo is not a test of the effectiveness of antidepressants as a category. And there is a well-known study, called the Sequenced Treatment Alternatives to Relieve Depression, or STAR*D trial, in which patients were given a series of different antidepressants. Though only thirty-seven per cent recovered on the first drug, another nineteen per cent recovered on the second drug, six per cent on the third, and five per cent after the fourth—a sixty-seven-per-cent effectiveness rate for antidepressant medication, far better than the rate achieved by a placebo.
Kirsch suggests that the result in STAR*D may be one big placebo effect. He cites a 1957 study at the University of Oklahoma in which subjects were given a drug that induced nausea and vomiting, and then another drug, which they were told prevents nausea and vomiting. After the first anti-nausea drug, the subjects were switched to a different anti-nausea drug, then a third, and so on. By the sixth switch, a hundred per cent of the subjects reported that they no longer felt nauseous—even though every one of the anti-nausea drugs was a placebo.
Kirsch concludes that since antidepressants have no more effectiveness than sugar pills, the brain-chemistry theory of depression is “a myth.” But, if this is so, how should we treat depression? Kirsch has an answer: C.B.T. He says it really works.
Kirsch’s claims appeared to receive a big boost from a meta-analysis published in January in the Journal of the American Medical Association and widely reported. The study concludes that “there is little evidence” that antidepressants are more effective than a placebo for minor to moderate depression. But, as a Cornell psychiatrist, Richard Friedman, noted in a column in the Times, the meta-analysis was based on just six trials, with a total of seven hundred and eighteen subjects; three of those trials tested Paxil, and three tested imipramine, one of the earliest antidepressants, first used in 1956. Since there have been hundreds of antidepressant drug trials and there are around twenty-five antidepressants on the market, this is not a large sample. The authors of the meta-analysis also assert that “for patients with very severe depression, the benefit of medications over placebo is substantial”—which suggests that antidepressants do affect mood through brain chemistry. The mystery remains unsolved.
Apart from separating us unnecessarily from our money, it’s hard to see how a pill that does nothing can also be bad for us. If Kirsch is right and antidepressant drugs aren’t doing anything consequential to our brains, then it can’t also be the case that they are turning us into Stepford wives or Nietzsche’s “last men,” the sort of thing that worries Greenberg. By Kirsch’s account, we are in danger of bankrupting our health-care system by spending nearly ten billion dollars a year on worthless pills. But if Greenberg is right we’re in danger of losing our ability to care. Is psychopharmacology evil, or is it useless?
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