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Interaction of St John's wort with conventional drugs: systematic review of clinical trials

BMJ 2004; 329 doi: (Published 01 July 2004) Cite this as: BMJ 2004;329:27
  1. Edward Mills, graduate fellow1 (millsej{at},
  2. Victor M Montori, assistant professor2,
  3. Ping Wu, graduate fellow3,
  4. Keith Gallicano, associate director4,
  5. Mike Clarke, director5,
  6. Gordon Guyatt, professor of clinical epidemiology1
  1. 1 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada L8N 3Z5
  2. 2 Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
  3. 3 London School of Hygiene and Tropical Medicine, London WC1E 7HU
  4. 4 Biopharmaceutics, Watson Laboratories, PO Box 1900, Corona, CA 92878-1900, USA
  5. 5 UK Cochrane Centre, Oxford OX2 7LG
  1. Correspondence to: E Mills, McMaster Health Sciences Centre, Department of Clinical Epidemiology and Biostatistics, Room 2C12, 1200 Main Street West, Hamilton, ON, Canada L8N 3Z5


    Objective To determine the methodological quality of clinical trials that examined possible interactions of St John's wort with conventional drugs, and to examine the results of these trials.

    Characteristics of methods used in 22 reviewed studies

    View this table:

    Design Systematic review.

    Data sources Electronic databases from inception to April 2004, reference lists from published reports, and experts in the field.

    Study selection Eligible studies were prospective clinical trials evaluating the pharmacokinetic effect of St John's wort on the metabolism of conventional drugs.

    Data extraction Two reviewers selected studies for inclusion and independently extracted data.

    Data synthesis 22 pharmacokinetic trials studied an average of 12 (SD 5) participants; 17 trials studied healthy volunteers and five studied patients. Most (17) studies used a “before and after” design; four studies used control groups other than the active group. Three studies randomised the sequence of administration or the participants to study arms or periods; three studies blinded participants or investigators. In 15 trials, investigators independently assayed the herb. Of 19 trials with available plasma data, three found no important interaction (change in area under the curve < 20%) and 17 found a decrease in systemic bioavailability of the conventional drug; in seven studies the 95% confidence interval excluded a decrease of < 20%.

    Conclusion Clinicians and patients should beware of possible decreases in the systemic bioavailability of conventional drugs when taken concomitantly with St John's wort.


    • Embedded Image A flow chart showing selection of studies for inclusion and a table with further details about the studies are on

    • Contributors The study was conceptualised by EM, VMM, and GG; EM and PW did the literature searches; EM, PW did the data abstraction; VMM, EM, and PW did the analysis; and EM, VMM, MC, GG, and KG wrote and critically revised the manuscript. EM will act as guarantor of this manuscript.

    • Funding This study was funded by the Ontario HIV Treatment Network.

    • Competing interests None declared.

    • Ethical approval Not required.

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