Placebo Power

Scientists explain why placebo response to antidepressants is so high, especially in young people.

By Darby Saxbe Ph.D., published on September 1, 2004 - last reviewed on June 9, 2016

Are antidepressant ads so ingenious that they've convinced the public of the drugs' efficacy—even those who aren't taking the medications?

Studies comparing placebos to medications often find that the people given fakes get better, too. It's a widespread, if little understood, clinical phenomenon and, oddly, the ranks of placebo responders seem to be growing, perhaps because of our heightened expectations for drugs.

When B. Timothy Walsh, a Columbia University psychiatrist, reviewed 75 trials of antidepressants conducted between 1981 and 2000, he found that, on average, 30 percent of people given placebos improved. This response rate increased about 7 percent per decade; the response rate to real drugs also went up, but not as sharply.

Placebo response to antidepressants is particularly high in young people. A clinical trial for Zoloft found improvements in 59 percent of children given a placebo, compared with 69 percent of the kids taking the drug.

Jon-Kar Zubieta, a University of Michigan researcher, explains that because young people have had fewer bouts with depression, the disorder may not have etched itself as deeply onto their brains. "Placebos may work by activating the circuits in your brain that relate to mood and affective states," says Zubieta. "Someone who is severely depressed and has had the illness longer won't respond as well, because those circuits are more disrupted." The placebo effect could also stem from the attention and support built into clinical trials; younger patients may respond especially strongly to that extra adult interest.

In adults, Walsh speculates that the changing populace that participates in clinical studies may be responsible for the rise in placebo response. Twenty years ago, before antidepressants entered the mainstream, drug trials included only the severely depressed. Nowadays, Walsh says, "people with milder and more transient forms of depression are coming into studies." These mild cases tend to respond best to placebos.

People who get better with sugar pills make life difficult for drug companies, who must meet Food and Drug Administration standards for efficacy by proving that their drugs work significantly better than placebos. In fact, a study led by University of Connecticut researcher Irving Kirsch looked at 47 trials of major antidepressants—drugs like Prozac, Zoloft and Paxil—and found the drugs conclusively beat out placebos only about half the time.

A University of California, Los Angeles study is in the works to figure out what placebo responders have in common, with an eye toward weeding them out of clinical trials.