| Home | Article Database | Fun Stuff | Resources | Tools & Calculators | Search HY

Ask the Mental Health Expert Archives 2001-2004

Expert Home  |  Archives by Date  |  Search Expert Archives  |  For Professionals  |  For Consumers

Placebos vs. Antidepressants

Q. A highly publicized report that placebos actually work better than antidepressants for many patients. This has undoubtedly caused some patients to wonder if they should continue taking antidepressants, particularly if they've seen no improvement or are bothered by side effects. Could you comment on the claim from this report?

A. I assume you are referring to the recent, much-publicized study by the Hypericum Depression Trial Study Group, published in the Journal of the American Medical Association (April 10, 2002). This was actually a study meant to assess the antidepressant effects of the popular herbal preparation, St. John's Wort.

Outpatients (N=340) were randomly assigned to receive H perforatum (St. John's wort), placebo, or sertraline (as an active comparator) for 8 weeks. Based on clinical response, the daily dose of H perforatum could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg. Responders at week 8 could continue blinded treatment for another 18 weeks.

The main outcome measure was change in the Hamilton Depression Rating Scale. Full response occurred in 31.9% of the placebo-treated patients vs. 23.9% of the H perforatum-treated patients (P =.21) and only 24.8% of sertraline-treated patients (P =.26). However, sertraline was better than placebo on the CGI (Clinical Global Impression) improvement scale (P =.02), which was a secondary measure in this study.

These results were certainly surprising, at least with respect to the SSRI antidepressant, sertraline. This had been shown effective in a number of previous placebo-controlled studies--otherwise, the FDA would never have approved it. This suggests that there were problems with the JAMA study itself. Two possibilities: the study was too short (it may take 12 weeks of more for some patients to respond to SSRI antidepressants), and/or the dose of sertraline used was too low (dosing for more resistant major depression goes up to 200 mg/day).

In short, I wouldn't draw too many conclusions from this study. Furthermore, numerous meta-analyses (in which dozens of studies are lumped together and the total effect size calculated) have demonstrated that antidepressant medications of various types are clearly more effective than placebo for major depression. See, e.g., Gerson et al, Harv Rev Psychiatry. 1999 May-Jun;7(1):1-28; and Davis et al Psychopharmacol Bull 1993;29(2):175-81.

In the latter study--a metaanalysis of approximately 300 studies of antidepressant treatment--the authors concluded that "Efficacy is proven beyond a shadow of a doubt." It's too bad that the favorable studies don't make as big a splash in the media as the rare clunkers.

July 2002

Disclaimer Back to Ask the Expert