The effectiveness of antidepressants is mainly in the placebo effect of treatment, not in the medication itself, according to a new study by Irving Kirsch.

Seventy-five percent of the response to medication for depression was a result of the patient being in treatment, while at the most 25 percent of the response was a true drug effect, asserts the study by Kirsch, a professor of psychology, and former UConn graduate student Guy Sapirstein.

"This means that for a typical patient, 75 percent of the benefit obtained from the active drug would also have been obtained from an inactive placebo," Kirsch says. "Whether the remaining 25 percent of the drug response is a true effect of the drug or a psychologically triggered response to side effects alone cannot yet be determined."

More placebos have been administered to research participants than any single experimental drug. "However, although almost everyone controls for placebo effects, almost no one evaluates them," he says. "With this in mind, we set about the task of evaluating the magnitude of the placebo response to antidepressant medication."

The study analyzed the possibility that antidepressants serve as active placebos, which produce side effects but do not cause any actual drug effect on the problem.

"Data from other studies indicate that most participants in studies of antidepressant medication are able to deduce whether they have been assigned to the drug condition or the placebo condition," according to the study.

"This study suggests that antidepressants might function as active placebos, in which the side effects amplify the placebo effect by convincing patients that they are receiving a potent drug," Kirsch says. "So if a patient takes a pill that causes side effects, he or she feels better because they believe they have been given an actual antidepressant and that the pill must be working."

The study, Listening to Prozac but Hearing Placebo: A Meta-Analysis of Antidepressant Medication, was published in the electronic journal Prevention & Treatment, http://journals.apa.org/prevention/, a publication of the American Psychological Association.

Kirsch and Sapirstein analyzed the changes in 2,318 patients whose primary diagnosis was depression and who had been randomly assigned to either antidepressant medication or placebo in 19 double-blind clinical trials. Sapirstein, a graduate student when they conducted the study, is now a psychologist at Westwood Lodge Hospital in Needham, Mass.

The study was a meta-analysis, a way of mathematically combining results from different studies with different measures. The analysis included 19 studies in which a total of 858 participants received placebos and 1,460 participants received medication. Medication included antidepressants such as Prozac and imipramine and potentially active placebos such as lithium.

Renu Aldrich