Hypericum

Abstract: St. John's wort (Hypericum perforatum) is an herbal remedy used widely for the treatment of depression. Recent clinical studies demonstrate that hypericum extracts increase the metabolism of various drugs, including combined oral contraceptives, cyclosporin, and indinavir. In this report, we show that hyperforin, a constituent of St. John's wort with antidepressant activity, is a potent ligand (Ki = 27 nM) for the pregnane X receptor, an orphan nuclear receptor that regulates expression of the cytochrome P450 (CYP) 3A4 monooxygenase. Treatment of primary human hepatocytes with hypericum extracts or hyperforin results in a marked induction of CYP3A4 expression. Because CYP3A4 is involved in the oxidative metabolism of >50% of all drugs, our findings provide a molecular mechanism for the interaction of St. John's wort with drugs and suggest that hypericum extracts are likely to interact with many more drugs than previously had been realized.

Abstract: Background In some countries extracts of the plant Hypericum perforatum L. (popularly called St. John's wort) are widely used for treating patients with depressive symptoms. Objectives To investigate whether extracts of hypericum are more effective than placebo and as effective as standard antidepressants in the treatment of major depression; and whether they have fewer adverse effects than standard antidepressant drugs. Search methods Trials were searched in computerised databases, by checking bibliographies of relevant articles, and by contacting manufacturers and researchers. Selection criteria Trials were included if they: (1) were randomised and double-blind; (2) included patients with major depression; (3) compared extracts of St. John's wort with placebo or standard antidepressants; (4) included clinical outcomes assessing depressive symptoms. Data collection and analysis At least two independent reviewers extracted information from study reports. The main outcome measure for assessing effectiveness was the responder rate ratio (the relative risk of having a response to treatment). The main outcome measure for adverse effects was the number of patients dropping out due to adverse effects. Main results A total of 29 trials (5489 patients) including 18 comparisons with placebo and 17 comparisons with synthetic standard antidepressants met the inclusion criteria. Results of placebo-controlled trials showed marked heterogeneity. In nine larger trials the combined response rate ratio (RR) for hypericum extracts compared with placebo was 1.28 (95% confidence interval (CI), 1.10 to 1.49) and from nine smaller trials was 1.87 (95% CI, 1.22 to 2.87). Results of trials comparing hypericum extracts and standard antidepressants were statistically homogeneous. Compared with tri- or tetracyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), respectively, RRs were 1.02 (95% CI, 0.90 to 1.15; 5 trials) and 1.00 (95% CI, 0.90 to 1.11; 12 trials). Both in placebo-controlled trials and in comparisons with standard antidepressants, trials from German-speaking countries reported findings more favourable to hypericum. Patients given hypericum extracts dropped out of trials due to adverse effects less frequently than those given older antidepressants (odds ratio (OR) 0.24; 95% CI, 0.13 to 0.46) or SSRIs (OR 0.53, 95% CI, 0.34-0.83). Authors' conclusions The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.

Abstract: Rationale: St. John's wort (Hypericum perforatum) has recently gained popularity as an alternative treatment for mild to moderate depression. Given the current widespread use of this herbal remedy, it is important for medical professionals to understand the potential pharmacological pathways through which Hypericum may exert an antidepressant effect. Objectives: (1) To review the current pharmacological, toxicological, and clinical literature available on Hypericum, and (2) to provide a synthesis of this information into a form that may be easily used by health care providers. Method: A comprehensive review of the recent scientific literature (January 1990–March 2000) was performed using the following electronic databases and reference publications: MEDLINE, The Cochrane Library, HealthSTAR, Current Contents (all editions), European Scientific Cooperative on Phytotherapy monographs, German Commission E monographs, and the Physicians' Desk Reference for Herbal Medicines, 1st edition. Results: One hundred and seven (107) publications in the English language and three publications in German were included in the review. Collectively, the data suggest that therapeutic preparations of Hypericum extract appear to exert potentially significant pharmacological activity within several neurochemical systems believed to be implicated in the pathophysiology of depression. However, little information exists regarding the safety of Hypericum, including potential herb–drug interactions. Conclusions: Additional research on the pharmacological and biochemical activity of Hypericum and its several bioactive constituents is necessary to further elucidate the mode(s) of antidepressant action. Given what is currently known and unknown about the biological properties of Hypericum, those who choose to use this herb should be closely monitored by a physician.