- A Szegedi, managing senior physician1,
- R Kohnen, head of scientific affairs2,
- A Dienel, head of clinical trials department3,
- M Kieser, head of biometry department ()3
- 1 Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Department of Psychiatry and Psychotherapy, Eschenallee 3, 14050 Berlin, Germany
- 2 Institute for Medical Research Management and Biometrics GmbH, Scheurlstraße 21, 90478 Nürnberg, Germany
- 3 Dr Willmar Schwabe Pharmaceuticals, PO Box 410925, 76209 Karlsruhe, Germany
- Correspondence to: M Kieser
- Accepted 17 December 2004
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 ≥ 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-Åsberg 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.
We thank the investigators and patients, St Klement for project management, T Konstantinowicz for the data analysis, T Utz for project assistance, and A Völp for help with the manuscript.
Contributors AS and RK conceived the study. AD conceived the study, and participated in its design and coordination. MK participated in the design of the study and was responsible for the analysis. All authors read and approved the final manuscript. AD and MK are guarantors.
Funding Dr Willmar Schwabe Pharmaceuticals, manufacturer of WS 5570.
Competing interests AS has received consultancy fees from Dr Willmar Schwabe Pharmaceuticals. RK is head of a contract research organisation (IMEREM), which is engaged in several clinical trials of hypericum extract for different pharmaceutical companies. AD and MK are employees of Dr Willmar Schwabe Pharmaceuticals.
Ethical approval The protocol was approved by the participating centres' appropriate independent ethics committees.