ST-JOHNS-WORT IN MILD-TO-MODERATE DEPRESSION - THE RELEVANCE OF HYPERFORIN FOR THE CLINICAL EFFICACY

In a randomized, double-blind, placebo-controlled, multicenter study, the clinical efficacy and safety of two different extracts of St. John 's wort were investigated in 147 male and female outpatients suffering from mild or moderate depression according to DSM-IV criteria. Follow ing a placebo run-in period of three to seven days, the patients were randomized to one of three treatment groups: During the 42-day treatme nt period, they received 3 x 1 tablets of either placebo, Hypericum ex tract WS 5573 (300 mg, with a content of 0.5% hyperforin), or Hypericu m extract WS 5572 (300 mg, with a content of 5% hyperforin). The manuf acturing process for the two Hypericum preparations was identical, so that they differed only in their hyperforin content. Efficacy regardin g depressive symptoms was assessed on days 0, 7, 14, 28, and 42, using the Hamilton Rating Scale for Depression (HAMD, 17-item version) and the Depression Self-Rating Scale (D-S) according to von Zerssen. In ad dition, the severity of illness was also rated by the investigators on days 0 and 42 using the Clinical Global Impression (CGI) scale. The l ast observation of patients withdrawn from the trial prematurely was c arried forward. At the end of the treatment period (day 42), the patie nts receiving WS 5572 (5% hyperforin) exhibited the largest HAMD reduc tion versus day 0 (10.3 +/- 4.6 points; mean +/- SD), followed by the WS 5573 group (0.5% hyperforin; HAMD reduction 8.5 +/- 6.1 points) and the placebo group (7.9 +/- 5.2 points). As regards the change in the HAMD total score between day 0 and treatment end and its relationship to the hyperforin dose, a significant monotonic trend was demonstrated in the Jonckheere-Terpstra test (p=0.017). In pairwise comparisons, W S 5572 (5% hyperforin) was superior to placebo in alleviating depressi ve symptoms according to HAMD reduction (Mann-Whitney U-test: p=0.004) , whereas the clinical effects of WS 5573 (0.5% hyperforin) and placeb o were descriptively comparable. These results show that the therapeut ic effect of St. John's Wort in mild to moderate depression depends on its hyperforin content.