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Popular Herbal Antidepressant Implicated in Drug Interactions
By Donald J. Brown, ND

Healthnotes Newswire —While clinical trials continue to demonstrate the success of St. John’s wort (Hypericum perforatum) in treating mild to moderate cases of depression,1 2 growing evidence suggests that consumers wishing to use the herbal antidepressant should be aware of potential drug interactions.

Recently published case studies in the British journal Lancet make a strong case that transplant patients taking the antirejection drug cyclosporine should completely avoid St. John’s wort.3 Doctors working in a transplant unit in Hannover, Germany, discovered that a patient whose cyclosporine levels were unexpectedly low had been taking St. John’s wort. After the St. John’s wort was discontinued, blood levels of cyclosporine returned to normal. These doctors therefore asked other transplant patients with low blood levels of cyclosporine whether they, too, were taking the herbal antidepressant. They identified 35 kidney and 10 liver transplant patients whose blood concentrations of cyclosporine had inexplicably dropped while they were taking St. John’s wort.

Cyclosporine is taken by transplant patients to fend off the immune system’s tendency to reject a transplanted organ. As blood levels of the drug decrease, the risk of organ rejection rises. The tendency for blood levels of the drug to decrease when people start taking St. John’s wort has been reported in several other cases as well.4 5 6

Other reports of drug interactions in the medical literature have extended to the protease inhibitor indinavir (Crixivan®), which is used to treat people with HIV infection,7 as well as digoxin, warfarin (Coumadin®), theophylline, and birth control pills.8 9

While a consensus is still lacking as to why these interactions occur, evidence appears to point to fact that St. John’s wort is likely interacting with special enzymes in the liver that are responsible for metabolizing (breaking down) drugs.10 11 Known as the cytochrome P450 system, these enzymes are the body’s way of ensuring normal clearance of drugs from the body once they’ve done their job. St. John’s wort appears to induce some of these enzymes to act a bit more quickly than normal, leading to a drop in normal blood levels of some medications.

In addition to the medications previously listed, individuals should discuss the use of St. John’s wort with their doctor or pharmacist if they are taking anti-anxiety drugs, sleep medications, heart medications such as nifedipine (Procardia®, Adalat®), cortisone and related drugs (internally), nonsedating antihistamines, estrogens, carbamazepine (Tegretol®), or ketoconazole (Nizoral®; internally).

As is the case with drug-drug interactions, knowledge of potential herb-drug interactions is important for people choosing to use herbal supplements. Armed with this knowledge, consumers should be able to make a more informed choice about whether to use St. John’s wort.

References
1. Woelk H. Comparison of St. John’s wort and imipramine for treating depression: randomized controlled trial. BMJ 2000;321:536–9.
2. Schrader D. Equivalence of St. John’s wort extract (ZE 117) and fluoxetine: a randomized, controlled study in mild–moderate depression. Internatl Clin Psychopharmacol 2000;15:61–8.
3. Breidenbach T, Hoffmann MW, Becker T, et al. Drug interaction of St. John's wort with ciclosporin. Lancet 2000;355:1912 [letter].
4. Barone GW, Gurley BJ, Ketel BL, et al. Drug interaction between St. John’s wort and cyclosporine. Ann Pharmacother 2000;34:1013–6.
5. Ruschitzka F, Meier P, Turina M, et al. Acute transplant rejection due to Saint John’s wort. Lancet 2000;355:548–9 [letter].
6. Safety of St. John’s wort (Hypericum perforatum). Lancet 2000;355:575–7 [letters to the editor from various authors].
7. Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St. John’s wort [letter]. Lancet 2000;355:547–8.
8. Ernst E. Second thoughts about safety of St. John’s wort. Lancet 1999;354:2014–6 [letter].
9. Brown D. St. John’s wort implicated in new drug interaction information—sorting through the facts. Healthnotes Rev Comp Integrative Med 2000;7:97–9.
10. Roby CA, Anderson GD, Kantor E, et al. St. John’s wort: Effect on CYP3A4 activity. Clin Pharmacol Ther 2000;67:451–7.
11. Moore LB, Goodwin B, Jones SA, et al. St. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Acad Sci USA 2000;97:7500–2.

Donald Brown, ND, is a naturopathic physician and one of the leading authorities in the United States on evidence-based herbal medicine. He is the founder and director of Natural Product Research Consultants, Inc., and serves on the Advisory Board of the American Botanical Council and the President’s Advisory Board of Bastyr University.




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