Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine.

OBJECTIVE To investigate the efficacy of hypericum extract WS 5570 (St John's wort) compared with paroxetine in patients with moderate to severe major depression. DESIGN Randomised double blind, double dummy, reference controlled, multicentre non-inferiority trial. SETTING 21 psychiatric primary care practices in Germany. PARTICIPANTS 251 adult outpatients with acute major depression with total score > or = 22 on the 17 item Hamilton depression scale. INTERVENTIONS 900 mg/day hypericum extract WS 5570 three times a day or 20 mg paroxetine once a day for six weeks. In initial non-responders doses were increased to 1800 mg/day hypericum or 40 mg/day paroxetine after two weeks. MAIN OUTCOME MEASURES Change in score on Hamilton depression scale from baseline to day 42 (primary outcome). Secondary measures were change in scores on Montgomery-Asberg depression rating scale, clinical global impressions, and Beck depression inventory. RESULTS The Hamilton depression total score decreased by mean 14.4 (SD 8.8) points, corresponding to 56.6% (SD 34.3%) of the baseline value, in the hypericum group and by 11.4 (SD 8.6) points (44.8% (SD 33.5%) of baseline value) in the paroxetine group (intention to treat analysis; similar results were observed in the per protocol analysis). The intention to treat analysis (lower one sided 97.5% confidence limit 1.5 points for the difference hypericum minus paroxetine) and the per protocol analysis (lower confidence limit 0.7 points) showed non-inferiority of hypericum and statistical superiority over paroxetine. The lower limits in both cases exceeded the pre-specified non-inferiority margin of -2.5 points and the superiority margin of 0. The incidence of adverse events was 0.035 and 0.060 events per day of exposure for hypericum and paroxetine, respectively. CONCLUSIONS In the treatment of moderate to severe major depression, hypericum extract WS 5570 is at least as effective as paroxetine and is better tolerated.