Effectiveness of St John's Wort in major depression - A randomized controlled trial

Context Extracts of St John's wort are widely used to treat depression. Alt hough more than 2 dozen clinical trials have been conducted with St John's wort, most have significant flaws in design and do not enable meaningful in terpretation. Objective To compare the efficacy and safety of a standardized extract of S t John's wort with placebo in outpatients with major depression. Design and Setting Randomized, double-blind, placebo-controlled clinical tr ial conducted between November 1998 and January 2000 in 11 academic medical centers in the United States. Participants Two hundred adult outpatients (mean age, 42.4 years; 67.0% fem ale; 85.9% white) diagnosed as having major depression and having a baselin e Hamilton Rating Scale for Depression (HAM-D) score of at least 20. Intervention Participants completed a 1-week, single-blind run-in of placeb o, then were randomly assigned to receive either St John's wort extract (n= 98; 900 mg/d for 4 weeks, increased to 1200 mg/d in the absence of an adequ ate response thereafter) or placebo (n=102) for 8 weeks. Main Outcome Measures The primary outcome measure was rate of change on the HAM-D over the treatment period. Secondary measures included the Beck Depr ession Inventory (BDI), Hamilton Rating Scale for Anxiety (HAM-A), the Glob al Assessment of Function (CAF) scale, and the Clinical Global impression-S everity and -Improvement scales (CGI-S and CGI-I). Results The random coefficient analyses for the HAM-D, HAM-A, CGI-S, and CG I-I all showed significant effects for time but not for treatment or time-b y-treatment interaction (for HAM-D scores, P<.001, P=.16, and P=.58, respec tively). Analysis of covariance showed nonsignificant effects for BDI and G AF scores. The proportion of participants achieving an a priori definition of response did not differ between groups. The number reaching remission of illness was significantly higher with St John's wort than with placebo (P= .02), but the rates were very low in the full intention-to-treat analysis ( 14/98 [14.3%] vs 5/102 [4.9%], respectively), St John's wort was safe and w ell tolerated. Headache was the only adverse event that occurred with great er frequency with St John's wort than placebo (39/95 [41%] vs 25/100 [25%], respectively). Conclusion In this study, St John's wort was not effective for treatment of major depression.