Antidepressants and the Placebo Effect, Revisited

For some time, concerns have been raised about the “placebo effect” in the pharmacotherapy of depression, a phenomenon that has been well documented in many placebo-controlled clinical trials of antidepressants. Too often, there have been media reports on the topic that are vastly oversimplified, implying that antidepressants are no better than a “sugar pill.” The matter was kicked into the news again in the summer of 2011 with the publication in the New York Review of Books of a two-part article by Marcia Angell. One of the books discussed by Angell was The Emperor’s New Drugs: Exploding the Antidepressant Myth by Irving Kirsch (Basic Books, 2010), in which Kirsch summarized meta-analyses of randomized, controlled trials of antidepressants. Focusing mostly on “mild” depression, Kirsch argued that since antidepressants have little specific efficacy, their use is rarely justified.

The situation quieted down for a while, but APA was then contacted by CBS, outlining a plan for a segment on “60 Minutes” on the placebo effect; the plan included interviewing Kirsch and several others. I was scheduled for an in-person interview, but CBS cancelled it at the last minute. We heard nothing for several months and were then surprised to get a call from CBS saying that the segment had been completed and that it would be shown on February 10. Fortunately, CBS included in the “60 Minutes” episode a brief interview with Michael Thase, an APA member and a leading expert in this area, who made the critical point that antidepressants do work, particularly for patients with severe depressive illnesses, and that there are many complexities in the methodology of published studies that raise questions about Kirsch’s conclusions.

In fairness, correspondent Leslie Stahl urged viewers that if they were taking antidepressants, they should talk to their doctors before making any change in their treatment. However, in my opinion the “take-home message” to the average viewer was that Kirsch had courageously revealed the truth—that is, that antidepressants don’t help most people who take them. As many of you may have seen, APA issued a press release on February 22, characterizing the CBS program as misleading and irresponsible. I subsequently wrote to the producer of “60 Minutes” and conveyed serious concerns about the coverage, emphasizing that antidepressants have been shown to be particularly effective for patients at highest risk for suicide, with the most severe forms of depression. I also pointed out that too often the public response to this kind of media report is to equate placebo with a “sugar pill,” whereas in fact patients taking placebos in carefully designed studies are participating in a treatment program that involves visits with caring professionals, in a fabric of support and hope. I pointed out that in the APA practice guideline, the recommended evidence-based treatment for mild to moderate depression is psychotherapy, and that no mention was made on “60 Minutes” of this standard of care. I emphasized that many patients taking antidepressants are doing well, often receiving help from their primary care physician or family physician, and that the program could influence them to stop taking medication and even to discontinue regular visits with their physician, potentially leading to serious consequences. I requested that CBS post my letter on its Web site, but I received a reply from the producer saying that he had spoken to his editors and that “we stand by our report.”

I have just returned from an excellent meeting of the American College of Psychiatrists, and one of the plenary presentations was given by Michael Thase, titled “Do Antidepressants Really Work? A Review of the Recent Controversy.” The presentation was an in-depth review of the problem and an analysis of the challenges in placebo-controlled trials. He pointed out that between 1995 and 2005, the use of antidepressants had doubled in this country, and that the use of counseling and psychotherapy had decreased significantly during the same period. After reinforcing the point that placebo treatment in a clinical trial involves many elements of “real” supportive therapy, Thase stated that for the milder forms of depression, “the care you provide is more important than the drug itself,” that is, that the nonspecific effect dwarfs the specific effect. (Thase ME. The Small Specific Effects of Antidepressants in Clinical Trials: What Do They Mean to Psychiatrists? Curr Psychiatry Rep. 2011; 6:476-482) He indicated that his “take-home message” was “take good care of your patient!”

With which I entirely agree! But in addition, antidepressants are crucial in the treatment of severe depression, often leading to remission, relapse prevention, and the saving of lives. Our most important message, one that I hope the media will endorse, is that patients who need treatment should get it, and that we have evidence-based treatments that work.