Ixst Johns Wort Hypericum Perforatum

St. John's wort is used mostly for mild to moderate depression. There are numerous systematic reviews of St. John's wort. The first meta-analysis (17) included 23 RCTs with a total of 1757 patients. The methodological quality of trials was variable but some were excellent. The results of the meta-analysis clearly showed that St. John's wort is more effective than placebo or as effective as synthetic antidepressants. This finding has been confirmed by several subsequent systematic reviews. The evidence comparing St. John's wort with conventional antidepressants is, however, still relatively weak. Recently, several RCTs have produced negative results. It is important to note that these related to severe rather than mild to moderate depression. The authors of the original meta-analysis (17) concluded that''extracts of Hyper-

icum are more effective than placebo in the treatment of mild to moderate depression.'' This conclusion still holds and is corroborated by new trial data that have become available since then (18).

A systematic review of the safety of St. John's wort (19) pooled all relevant data from case reports, clinical trials, postmarketing surveillance, and drug-monitoring studies. Collectively this evidence suggested that St. John's wort is well tolerated with an incidence of adverse effects similar to that of placebo. The most common adverse effects were gastrointestinal symptoms, dizziness/confusion, and tiredness/sedation. A potentially serious adverse effect is photosensitivity, but this appears to occur extremely rarely. Since the publication of this review we have learned much about the interactions between St. John's wort and other drugs (20). Extracts of St. John's wort activate enzymes of the cytochrome P450 system, namely CYP3A4. It can therefore lower the plasma levels of a range of drugs given concomitantly; cyclosporin, oral contraceptives, phenoprocoumon, warfarin, amitriptyline, indinavir, and digoxin. When used with other SSRIs it can cause a serotonin syndrome.

On balance, the benefits of St. John's wort as a symptomatic treatment of mild to moderate depression outweigh its risks—provided, of course, that these risks are managed adequately. Essentially St. John's wort should not be combined with drugs metabolized via the cytochrome P450 enzyme system.

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