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Study Shows St. John's Wort Ineffective for Major Depression of Moderate Severity

An extract of the herb St. John's wort (Hypericum perforatum) was no more effective for treating major depression of moderate severity than placebo, according to research published in the Journal of the American Medical Association. St. John's wort is widely used for depression, but scientific evidence on its effectiveness has been inconsistent. This study, funded jointly by NCCAM, the National Institute of Mental Health, and the NIH Office of Dietary Supplements, compared a standardized extract of St. John's wort with a placebo. As a way of assessing the trial's ability to detect antidepressant effects, the researchers also compared the antidepressant drug sertraline with placebo.

Researchers enrolled 340 participants who had been diagnosed with major depression of at least moderate severity. The study was conducted in two phases. The first phase, lasting 8 weeks, measured the number of participants whose depression responded to treatment with St. John's wort (from 900 mg to 1,500 mg per day), sertraline (50 mg to 100 mg per day), or placebo; this phase was the primary focus of the study. A second phase offered participants who had responded to their initial treatment another 18 weeks of therapy.

The primary outcomes of the study, assessed during the first phase, were average change in Hamilton Depression Scale (HAM-D) scores; and percent of participants with a full response to treatment, based on HAM-D and Clinical Global Impressions-Improvement Scale (CGI-I) scores. The researchers found that HAM-D scores among participants taking St. John's wort dropped approximately 8.7 points on average versus about 9.2 points for placebo and 10.5 points for sertraline. They also found that approximately 24 percent of participants taking St. John's wort had full responses to treatment compared with placebo (32 percent) and sertraline (25 percent). On the primary outcome measures, neither St. John's wort nor sertraline was significantly different from placebo. On a secondary measure, CGI-I score alone, sertraline was better than placebo.

The researchers noted the importance of including both a placebo and a conventional antidepressant in their study. They concluded that their findings do not support the use of St. John's wort for major depression of moderate severity, and that without clear evidence of efficacy, people should not substitute St. John's wort for standard clinical care of this condition.


Additional Resources

Publication Date: 
April 10, 2002

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