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A promising new drug for depression failed to clear efficacy tests this year, illuminating a decades-old problem in psychopharmacology that deserves more study, researchers say
Last winter, psychiatrists and drug company executives were eagerly anticipating the arrival of a new product to fight depression. A novel compound-a Merck invention known as MK-869-then in several clinical trials, seemed set to become a new millennium drug for millions of people who take antidepressant medication every day. Results published in Science (11 September 1998, pp. 1624, 1640) had shown that it worked well and caused almost no sexual dysfunction, a side effect of many other pills on the market. Merck assured financial analysts in December that MK-869 was likely to be a big moneymaker. But on 22 January, those hopes were dashed when Merck, in an abrupt reversal, disclosed that MK-869 would be shelved as an antidepressant, although it may find a limited market as a treatment for nausea during chemotherapy. What went wrong?
Merck was struck by "the curse of the placebo effect," some researchers concluded. A Merck press release explained that when the company analyzed data from a new clinical trial in January, it found that patients who had received a dummy pill had done unexpectedly well. They did almost as well, in fact, as those on MK-869, wiping out the rationale for the new drug. The news was a downer for Merck and Wall Street: The price of the company's stock dropped 5% on the day Merck broke the news. It rebounded within the week, however, in part because Merck is already testing a new antidepressant that could be more potent and "much better than MK-869," according to Reynold Spector, executive vice president of Merck Research Laboratories in Rahway, New Jersey (see sidebar).
The MK-869 reversal may have been a temporary setback for Merck, but it highlights a chronic problem for psychopharmacology-the placebo effect. It's a phenomenon that bedevils many trials of antidepressant drugs, spoiling some and driving up the cost of others, as clinicians are forced to recruit more patients to obtain statistically significant data. Drug developers regard it as an occupational hazard that masks the ef fects of potentially useful compounds. But there's more to it than that. Some psychiatrists and clinical...