Level 1: Likely reliable evidence

A recent Cochrane systematic review evaluated the efficacy and safety of St. John’s wort extracts for the treatment of major depression (Cochrane Database Syst Rev. 2008[4]:CD000448). The review included 29 randomized trials comparing St. John’s wort with placebo (11 trials), standard antidepressants (12 trials), or both (six trials) in a total of 5,489 patients. In trials ranging from four to 12 weeks in duration with daily doses of 500-1,200 mg, response rates for St. John’s wort were similar to those for older antidepressants (tricyclics and tetracyclics) (48.6% vs. 48.8%) and for selective serotonin reuptake inhibitors (SSRIs) (52% vs. 52%) and superior to those for placebo (53.6% vs. 36.2%, P <.001, NNT 6). The placebo comparison was limited by significant heterogeneity among trials: While St. John’s wort was more effective than placebo in 11 trials from German-speaking countries, there were no differences in efficacy compared with placebo in seven trials from other countries. Variations in types of extract did not explain this difference in outcomes.

The primary safety outcome was the number of patients dropping out or discontinuing treatment due to adverse effects. St. John’s wort had significantly fewer dropouts than older antidepressants (2.4% vs. 9.8%, P <.0001, NNT 8) or SSRIs (3.4% vs. 6.8%, P <.005, NNT 30) and no difference compared with placebo. Standard doses of one component do not imply equivalence among products, since several components of the plant may contribute to the potential benefit. Note that serious drug interactions are possible when St. John’s wort is used with standard antidepressants and other medications.