The Ordinary Extraordinary blog
The Ordinary Extraordinary blog
The placebo effect (Pathologizing, part 2 of 6)
Now we continue our two week review of a recent article on the history and current state of psychotherapy and pharmaceutical use in society. The primary subject of today’s installment is the placebo effect, a phenomenon best illustrated in a study recounted within the article. In the study, “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.” Some thought-provoking ideas to digest there.
The article is “Head Case” by Louis Menand, published in the March 1, 2010 issue of The New Yorker. Below, we present the second of six installments.
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?
(The article will continue in part three.)
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Saturday, March 13, 2010