Clinical Question: In adults with moderate to severe major depression, is an extract of St. John’s wort as effective as paroxetine (Paxil) in the short term?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Concealed

Synopsis: Researchers enrolled 251 adult outpatients with a first or recurrent episode of major depression without psychotic features as demonstrated by symptoms persisting from two weeks to one year (average: 5.33 months) and a score of 22 or higher on the 52-point Hamilton Depression Scale. The products used were hypericum extract WS 5570 in a dosage of 300 mg three times per day standardized to contain 3 to 6 percent hyperforin and 0.12 to 0.28 percent hypericin (which is lower than the usual standard of at least 0.3 percent hypericins in U.S. products), and paroxetine in a dosage of 20 mg per day.

Patients were randomized to receive St. John’s wort or paroxetine with corresponding placebo for two weeks. Dosages were doubled at two weeks if an initial response was not seen, which occurred in 57 percent of patients receiving St. John’s wort and 48 percent of patients receiving paroxetine. At baseline, both groups averaged scores of 25.5 on the Hamilton Depression Scale; at the end of the study, scores had decreased by 14.4 in the St. John’s wort group and by 11.4 in the paroxetine group (one-sided P < .025). Scores on other measures of depression (i.e., Montgomery-Asberg scale, Beck Depression Self-Assessment Inventory) also were significantly better in the patients treated with St. John’s wort.

Reports of adverse effects, namely gastrointestinal and nervous system effects, were higher among patients treated with paroxetine (55 versus 76 percent; number needed to treat to harm = five).

Bottom Line: In patients who have moderate to severe depression, St. John’s wort is at least as effective as paroxetine after six weeks of therapy. It also is tolerated better than paroxetine. In this study, more than one half of the patients who received St. John’s wort required a dosage of 600 mg three times per day of a product containing a smaller amount of the purported active ingredients than is used commonly in other studies. Patients in clinical practice may experience a benefit at a dosage of 300 mg three times per day using commercial products that contain a larger amount of the active ingredients. (Level of Evidence: 1b)