Do Antidepressants Work?

Do antidepressant medications work? The question may seem an odd one to ask these days. More than one in 10 Americans have prescriptions for antidepressants, which rake in sales of almost $10 billion in the United States alone. Yet for years, researchers have questioned whether the intensively advertised drugs are truly effective. One of the first to cast doubt was psychologist Irving Kirsch, professor emeritus at the University of Connecticut and now a professor of psychology at the University of Hull in England. Widely regarded as one of the world’s leading experts on psychiatric drugs and the placebo effect, he is the author of The Emperor’s New Drugs, as well as more than 200 research papers.

The AARP Bulletin reached Kirsch at home in England to discuss his findings and the controversy they’ve sparked.

Q. Your studies suggest that antidepressants are no more effective than sugar pills, or placebos. How can that be?

A. Placebo effect is very powerful when you’re treating depression. Placebos offer hope. And one of the chief features of depressions is a sense of hopelessness, the belief that you’re not going to get better. Anything that instills a sense of hope will at least temporarily help treat depression. Our studies show that placebos are about 80 percent effective, which is exactly how effective antidepressants are in the short-term.

Q. But aren’t the newest generation of antidepressants designed to restore normal levels of serotonin in the brain?

A. The theory behind drugs such as Prozac and Paxil, which are selective serotonin re-uptake inhibitors, or SSRIs, is that depression is linked to low levels of serotonin. But most researchers have abandoned that theory. One reason is that the newest drugs are just about as effective as older drugs that don’t affect serotonin levels. In fact, a new antidepressant recently approved in France is a selective serotonin re-uptake enhancer. It has the opposite effect of drugs like Paxil or Prozac. And yet it appears to work just as well. That tells us the serotonin theory is wrong.

Q. Published in January in the Journal of the American Medical Association, a major study also cast doubt on the effectiveness of antidepressants. Does it add anything to the debate?

A. Yes. The conclusions of that study, led by researchers from the University of Pennsylvania, are almost exactly what we found. But the JAMA study is based on a completely different set of data. The fact that it came to the same conclusion shows that the findings are robust. All in all, this new study confirms and updates our conclusions.

Q. Obviously, these findings are controversial. Many doctors who prescribe antidepressants insist that they see benefits in their patients. Are they wrong?

A. Their perception is entirely right. People do get better on antidepressants. And they get better on placebos. But doctors don’t prescribe sugar pills. They prescribe medications. And when they see patients getting better, they naturally attribute that to the drug. They can’t compare antidepressants to placebos in their practices. They have no way of knowing how much of the benefit is placebo effect and how much is a chemical effect. For that, you do research.

Q. What’s the bottom line from your studies?

A. Antidepressants at best have a small and clinically insignificant effect for mild, moderate and even severe depression. The drugs may be slightly more effective than placebo for people with very severe depression, at the far end of the scale. But even that small difference may be a placebo effect.