Safety of St. John's Wort extract compared to synthetic antidepressants

Phytomedicine. 2006 Feb;13(3):199-204. doi: 10.1016/j.phymed.2005.07.005. Epub 2005 Nov 2.


The clinical efficacy of some standardized St. John's Wort extracts (SWEs) such as WS((R)) 5570, WS((R)) 5572 or LI 160 in the treatment of mild, moderate and severe major depression has been demonstrated in 38 controlled clinical trials and two recent meta-analyses. Sixteen post-marketing surveillance studies with such preparations, based on a total of 34,804 patients, recorded an incidence of adverse events (AEs) among patients between 0% and 6%. Of these studies, the four large-scale surveillance studies with a total of 14,245 patients recorded a rate of AEs ranging from 0.1% to 2.4% and a drop-out rate due to AEs of 0.1-0.9%. This is at least ten-fold lower than that recorded with synthetic antidepressants. AEs associated with SWE treatment were mild and transient in nearly all cases. As with synthetic antidepressants, pharmacokinetic interactions may occur occasionally as a result of activity changes of drug-metabolising and drug-transporting proteins, especially CYP 3A4 and P-gp. Risks to the patient are not caused by SWE but by drugs with a narrow therapeutic range. Consequently, SWE preparations should not be taken concurrently with other antidepressants, with coumarin-type anticoagulants, the immunosuppressants cyclosporine and tacrolimus, protease and reverse transcriptase inhibitors used in anti-HIV treatment or with certain antineoplastic agents. However, such cases are extremely rare and, with medical supervision, easily avoided. In conclusion, the safety of SWE must be considered more favourable than that of synthetic antidepressants.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / chemical synthesis
  • Antidepressive Agents / therapeutic use
  • Depression / drug therapy*
  • Dermatitis, Phototoxic / etiology
  • Food-Drug Interactions
  • Herb-Drug Interactions
  • Humans
  • Hypericum / adverse effects*
  • Phytotherapy / adverse effects*
  • Plant Extracts / adverse effects*
  • Plant Extracts / therapeutic use
  • Risk Assessment


  • Antidepressive Agents
  • Plant Extracts