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St. John's Wort Better than SSRI for Moderate to Severe Depression

Ƶ MedicalToday

St. John's wort (an extract of Hypericum perforatum) is known as an effective treatment for mild depression. A study published in The British Medical Journal this week is the first to suggest that it may also be an effective therapy for moderate to severe depression.


In this study St. John's wort was as effective as--and better tolerated than--Paxil (paroxetine) in the treatment of moderate to severe depression.

Action Points

  • Advise interested patients with moderate to severe depression that there is little evidence beyond this relatively small study that St. John's wort is effective for these types of depression. More research is needed before its effectiveness in these settings and its long-term efficacy and safety can be ascertained.
  • Furthermore, advise patients that St. John's wort supplements are not regulated by the Food and Drug Administration, so the strength and safety of various preparations in the US cannot be assured.
  • Advise patients who wish to use the herb that they should have their other medications reviewed as St. John's wort interacts with several prescription medicines to reduce their effectiveness.
  • Direct interested patients to the NIH's National Center for Complementary and Alternative Medicine website for information on St. John's wort:


Lead investigator A. Szegedi of Charite-Universiatmedizin Berlin noted that while this herbal treatment has shown efficacy in the treatment of mild to moderate depression, it has not been sufficiently tested for its effectiveness in patients with severe depression. Only one randomized, controlled trial has investigated this possibility, but according to Dr. Szegedi that trial was underpowered and its conclusions were not reliable.


To investigate whether St. John's wort extracts are as effective as an SSRI at treating moderate to severe depression, Dr. Szegedi and colleagues conducted a randomized, controlled, double-blind trial, comparing hypericum extract WS 5570 with Paxil.


The researchers gave half of 244 patients with severe depression WS 5570, 900 mg three times daily for 6 weeks. The other half received Paxil 20 mg daily. Treatment dose for patients who showed no relief of symptoms after 2 weeks of taking either treatment was increased, and patients were monitored for common side effects including abdominal pain, diarrhea, dry mouth, nausea, fatigue, dizziness, headache, sleep disorders, and increased sweating.


The researchers used a standard rating system (Hamilton depression score) to monitor the depression symptoms of the participants every 2 weeks during the study.


At the end of 6 weeks, half (61 out of 122) of those who took St. John's wort were in remission compared with a third (43 out of 122) of those taking Paxil. This difference was statistically significant. (P=.02)


In addition, the incidence of adverse events in the Paxil group was 1.72 times the rate seen for St. John's wort. (95% CI 1.42-2.10)


"Our results support the use of hypericum extract WS 5570 as an alternative to standard antidepressants in moderate to severe depression, especially as it is well tolerated," the authors wrote. Nevertheless, they stressed that their results need to be duplicated by others.


The researchers plan to study the efficacy of the herbal extract in the long-term treatment for depression. Given its better side effect profile, St. John's wort might be a better option for chronic depression than standard antidepressants, they noted.

Primary Source

British Medical Journal

A Szegedi, R Kohnen, A Dienel, M Kieser BMJ, doi:10.1136/bmj.38356.655266.82 (published 11 February 2005)