St John's wort and depression: slight efficacy at best, many drug interactions.

(1) St John's wort has been widely used for centuries as a herbal remedy. Dozens of trials, of variable quality, have examined the therapeutic value of St John's wort. Published meta-analyses show that St John's wort extracts are more effective than placebo in patients with mild and moderate depression. (2) Trials show that St John's wort is about as effective as tricyclic and serotonin reuptake inhibitor antidepressants. (3) There is insufficient evidence to determine the efficacy of St John's wort in patients with more severe depression. (4) Few, mostly minor adverse effects have been reported, but there may be a small risk of serotonin syndrome and cutaneous photosensitisation. (5) Some components of St John's wort interfere with CYP3A4, one of the main cytochrome P450 isoenzymes. CYP3A4 is involved in the metabolism of many commonly used drugs. St John's wort reduces the efficacy of several drug groups including: immunosuppressants (risk of graft rejection), oral contraceptives (risk of pregnancy), oral anticoagulants (risk of thrombosis), and HIV protease inhibitors. It can also reduce the bioavailability of digoxin. (6) In practice, St John's wort is an inappropriate treatment for severe depression. It is, however, an acceptable option for short-term management of transient depressed mood when there is no risk of drug interactions and when the patient is properly informed of this risk. (7) In short, the risk-benefit balance of St John's wort is no better than that of standard antidepressants, mainly because of the risk of drug interactions.