Depressing News on Antidepressants

Just for the record, reporters take no pleasure in questioning the power of drugs to treat depression. To the contrary: journalism is notorious for attracting curmudgeons, grumps and depressives—some of my best friends are one or more of the above—so we wish with all our hearts that antidepressants would work.

And that scientists wouldn't keep finding evidence that they do not.

In January I reported on the file-drawer effect in studies of antidepressants. The file-drawer effect refers to the fact that scientifically-sound studies on the efficacy of antidepressants are not published, as The New England Journal of Medicine article described. Most of those studies were negative—that is, the drugs did not help patients much more than a sugar pill (placebo) did, if they helped at all. That skews the perception of doctors, scientists and you and me about these drugs; basing our assessment of antidepressants on published studies alone is like evaluating the prowess of a baseball team when only its wins and not its losses are reported.

Now a team of scientists has examined many of those unpublished studies, obtained through a Freedom of Information Act request for the U.S. Food and Drug Administration. As many people feared, once you include the deep-sixed studies, antidepressants look hardly more effective than a placebo at lifting patients’ black cloud of despair.

For their analysis, scientists led by Irving Kirsch of Britain’s University of Hull started with the data dump they got from the FDA on fluoxetine

In short, there was virtually no difference in the response to drug vs. placebo of patients who suffered moderate levels of depression, and a small difference for patients with very severe depression, they report in the

The reason for the tiny, or nonexistent, differences? Patients respond so well to placebo—to the mere thought that something might be helping them—that there was little room for an actual drug to do more. Across all groups, response to placebo accounted for more than 80 percent of any improvement. (In contrast, the placebo response to pain drugs is estimated at about 50 percent.) That suggests that even when patients are taking and benefiting from, say, Zoloft, the vast majority of the improvement is due to what their minds are telling them—that is, the belief that they would be helped. Only the most depressed patients showed little placebo response.

The scientists conclude that there is little reason to prescribe the new antidepressants to any but the most severely depressed patients except as a last resort. Kirsch summarized the findings this way: “Although patients get better when they take antidepressants, they also get better when they take a placebo, and the difference in improvement is not very great. This means that depressed people can improve without chemical treatments.”

But it seems that there is a larger message here. The placebo response—the belief that treatment will make you better—is enormously powerful. Surely it’s time to investigate further how it works and how it can be harnessed.