Winston Churchill called it his “black dog.” British medical biologist Lewis Wolpert has described it as “the cancer of the emotions.” Once known politely as melancholia, it is more often referred to these days as clinical depression, and it has been estimated that as many as two-thirds of sufferers, even in developed countries, go undiagnosed and untreated. Here in Japan, concern about the steadily rising suicide rate has prompted the Health, Labor and Welfare Ministry to sponsor studies of better ways to identify and combat depression.
But there’s the rub. Precisely because the causes of depression are unclear, there is still no real consensus about the most effective treatment for it. The man in the street is likely to advise a depressed friend or colleague to “pull himself together,” take a vacation, or get more sleep and exercise. Some old-fashioned doctors may tell patients the same thing. Others advise alternative remedies: acupuncture or herbal regimens. Most, though, prescribe antidepressant drugs such as Prozac and Paxil, either alone or in combination with therapy. Numerous studies to date have indicated that the drugs do help people feel less depressed, although why they do is not clearly understood. At any rate, they are the closest thing we have to a generally agreed-upon treatment for depression.
That is, until this month, when a news story shattered — or seemed to shatter — even that emerging consensus. Last month, a Seattle psychiatrist published the results of his analysis of the placebo effect in scores of clinical trials undertaken between 1979 and 1996 by U.S. companies seeking government approval of antidepressant drugs. According to Dr. Arif Khan, sugar pills worked as well as the antidepressants more than half the time, and, what’s more, they triggered changes in the same parts of the brain as the medicines did.
Interesting? Yes. But even more interesting was the immediate general interpretation of what these results meant. We know we should take the news with a grain of salt, but some versions of this story called for a lot more than a grain. “Against depression, a sugar pill is hard to beat,” read the headline in one major U.S. daily. A columnist for another newspaper wrote that “after decades of use and thousands of clinical trials, and surely much to the chagrin of the companies making millions from antidepressants, it’s now clear that placebos are as effective (as) or even more effective than Prozac, Zoloft and Paxil in treating depression.” The implication was that people suffering from what Professor Wolpert calls “malignant sadness” might just as well throw their Prozac out the window. The cure is all in the mind. Beliefs, not chemicals, do the trick.
If that is so, then what was Dr. Khan doing telling a New York Times reporter last month that he personally had no doubt that antidepressant drugs worked, especially with severely ill patients who are normally excluded from clinical trials? “When you go out in the real world and look at treated patients and untreated patients . . ., believe me, the difference is very large,” he said. That does not sound like a man who thinks that antidepressants don’t work or that placebos work just as well.
As usual, the truth lay in the nuances. A closer reading of the study confirmed that, as in all drug trials, participating patients received far more time and attention than do ordinary patients in overcrowded clinics. Several earlier studies show that most people who are prescribed antidepressants do not receive therapy and that, understandably, they tend not to fare as well as people who do. Second, the trials typically lasted just two months. There is no evidence to suggest that patients taking placebos would do as well as patients taking medication over a longer period-and depression, of all ailments, is a long-term phenomenon. Many other clinical studies in fact suggest the opposite is true.
In a sense, the most striking implication of the Khan study was not that antidepressant drugs don’t work any better than placebos, but that placebos can work as well as antidepressants in certain situations. Care and concern are critical factors, but so, too, is a belief that drugs actually work. Paradoxically, the better the drugs, the stronger the placebo effect — as Prozac’s reputation for effectiveness grows, so does the effectiveness of placebos in clinical trials. No one, however, is suggesting that sugar pills can replace Prozac or its cousins; their effects are transient at best. A simpler, but more useful, conclusion to be drawn from the study’s findings is that doctors ought to find more time for each patient and that drugs — any drugs — work better in combination with therapy. Oh, and one more: Never swallow newspaper headlines whole.
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