We Have Happy Pills, Anxiety Drugs, and Therapists Galore: So Why Are We More Stressed and Depressed Than Ever?

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The only problem is that it probably isn’t true.

Like the dopamine hypothesis of schizophrenia and other attempts to attribute complex mental phenomena to simplistic biochemical causes, the serotonin hypothesis of depression is shaky at best. Several studies have established that lowering serotonin levels does not negatively impact mood. In fact, a new pharmaceutical known as tianeptine—sold in France and other European countries under the trade name Coaxil—has been shown to be as effective as Prozac. Tianeptine works by lowering synaptic serotonin. As psychology professor Irving Kirsch of the University of Hull in England told Newsweek, “If depression can be equally affected by drugs that increase serotonin and by drugs that decrease it, it’s hard to imagine how the benefits can be due to their chemical activity.”

It is, indeed, especially as evidence accumulates that, in most cases, SSRIs work no better than placebos to boost mood. The first such analysis, published in 1998, looked at thirty-eight manufacturer-sponsored studies that included more than three thousand depressed patients. It found negligible differences in improvement between those on the drugs and those on dummy pills. At least 75 percent of the benefit from this class of antidepressants seemed to be a placebo effect. This finding has since been confirmed by other research.

To say that biomedically minded physicians have been reluctant to accept this finding or modify their prescribing habits as a result would be a great understatement. Both professional and popular media have tried to play down the significance of this new research and in some cases have misreported the findings. In April 2002, the Journal of the American Medical Association (JAMA) published the results of a large randomized controlled study sponsored by the National Institutes of Health to evaluate a popular herbal treatment for depression, St. John’s wort ( Hypericum perforatum). Its effect was compared with that of the widely prescribed SSRI Zoloft (sertraline) and a placebo in 340 patients with major depressive disorder. The conclusion that made front-page news around the world was that St. John’s wort worked no better than the placebo at relieving depression. Television news shows featured reporters in health-food stores pointing to St. John’s wort products and advising consumers not to waste their money on natural remedies whose supposed benefits were nothing more than old wives’ tales.

Never mind that St. John’s wort is not indicated for the treatment of major depression, making the point of the study questionable. The finding from this well-designed trial that should have made front-page news was that Zoloft also worked no better than the placebo. In fact, the placebo treatment was acually more effective in these very depressed patients than either Zoloft or St. John’s wort!

Irving Kirsch summarized the growing body of evidence against SSRIs in his 2010 book, The Emperor’s New Drugs: Exploding the Antidepressant Myth, which I recommend. In response, proponents of the drugs and the serotonin hypothesis retreated to a more defensible position: SSRIs may owe much of their apparent benefit to patients’ belief in them, they admit, but they still have a real biochemical effect that makes them useful in the treatment of severe depression. Unfortunately for those proponents, the most recent analysis, published in the January 6, 2010, issue of JAMA, rates the real biochemical effect of SSRIs as nonexistent to negligible even in most cases of severe depression. Only in patients with very severe symptoms can researchers detect a statistically significant drug benefit compared with that of a placebo. About 13 percent of people with depression have very severe symptoms. One of the authors of the JAMA paper, Steven D. Hollon, Ph.D., of Vanderbilt University, has said, “Most people [with depression] don’t need an active drug. For a lot of folks, you’re going to do as well on a sugar pill or on conversations with your physicians as you will on medication. It doesn’t matter what you do; it’s just that you’re doing something.”