Comparison of St John's wort and imipramine for treating depression: randomised controlled trial

BMJ 2000; 321 doi: (Published 02 September 2000) Cite this as: BMJ 2000;321:536
  1. Helmut Woelk, medical director for the Remotiv/Imipramine Study Group
  1. Klinik für Psychiatrie und Psychotherapie, Akademisches Lehrkrankenhaus der Universität Giessen, Licher Strasse 106, D-35394 Giessen, Germany
  • Accepted 25 April 2000


Objectives: To compare the efficacy and tolerability of Hypericum perforatum (St John's wort extract) with imipramine in patients with mild to moderate depression.

Design: Randomised, multicentre, double blind, parallel group trial.

Setting: 40 outpatient clinics in Germany.

Participants: 324 outpatients with mild to moderate depression.

Intervention: 75 mg imipramine twice daily or 250 mg hypericum extract ZE 117 twice daily for 6 weeks.

Main outcome measures: Hamilton depression rating scale, clinical global impression scale, and patient's global impression scale.

Results: Among the 157 participants taking hypericum mean scores on the Hamilton depression scale decreased from 22.4 at baseline to 12.00 at end point; among the 167 participants taking imipramine they fell from 22.1 to 12.75. Mean clinical global impression scores at end point were 2.22 out of 7 for the hypericum group and 2.42 for the imipramine group. On the 7 point self assessments of global improvement completed by participants (score of 1 indicating “very much improved” and 7 indicating “very much deteriorated”) mean scores were 2.44 in the hypericum group and 2.60 in the imipramine group. None of the differences between treatment groups were significant. However, the mean score on the anxiety-somatisation subscale of the Hamilton scale (3.79 in the hypericum group and 4.26 in the imipramine group) indicated a significant advantage for hypericum relative to imipramine. Mean scores on the 5 point scale used by participants to assess tolerability (score of 1 indicating excellent tolerability and 5 indicating very poor tolerability) were better for hypericum (1.67) than imipramine (2.35). Adverse events occurred in 62/157 (39%) participants taking hypericum and in 105/167 (63%) taking imipramine. 4 (3%) participants taking hypericum withdrew because of adverse events compared with 26 (16%) taking imipramine.

Conclusions: This Hypericum perforatum extract is therapeutically equivalent to imipramine in treating mild to moderate depression, but patients tolerate hypericum better.


  • Funding Bayer AG supplied the study medication and sponsored the study through the clinical research organisation Beromed, Berlin, Germany.

  • Competing interests None declared. The interpretation of the results was entirely the prerogative of the principal investigator and the study group.

  • Embedded Image A full list of members of the study group can be found on the BMJ's website

  • Accepted 25 April 2000
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