Biological Therapies in Psychiatry Alan J. Gelenberg, M.D. Dr. Bob's Psychopharmacology Tips

St John's Wort: Nostrum for Depression?

Articles in the lay press, descriptions among people interested in alternative therapies, and Internet discussions among psychiatrists have recently attended to St John's wort (Hypericum perforatum), an herb that has been used for centuries as a mild tranquilizer and as a treatment for depression and insomnia. (The word "wort" is Old English for "plant.") In what might be the first English language review of Hypericum as an antidepressant, Ernst searched the literature for randomized, controlled trials on this subject. (1)

The author located 14 studies comparing St John's wort with placebo and another four in which it was compared with an antidepressant medication. Most of the studies were recent, in German, and in journals "unfamiliar to an international audience." Eight of the placebo-controlled trials met preset methodologic criteria, and all eight found Hypericum to be superior to placebo. Similarly, the three sufficiently rigorous antidepressant-controlled studies found comparable efficacy for the herb. In general, adverse reactions were minimal.

More recently, Linde and others published another literature review and meta-analysis of randomized controlled trials of St John's wort for depression. (2) Twenty-three randomized trials -- involving a total of 1757 outpatients, mostly with mild or moderate depression -- met their methodologic criteria for inclusion. There were 1008 patients in placebo-controlled trials, while another 749 were subjects in trials comparing Hypericum with other antidepressants or sedatives. Most trials lasted 4 to 8 weeks. Daily doses of hypericin (the presumed active ingredient of Hypericum) varied between 0.4 and 2.7 mg. The total extract dose range was 300 to 1000 mg/day.

In placebo-controlled trials providing data on "treatment responders, " 22% of subjects in the placebo group were considered responders versus 55% of those treated with Hypericum. The Hypericum group in the antidepressant-controlled studies had a 64% response rate compared with a 59% rate among patients taking standard antidepressant medications. Thirty-six percent of antidepressant-treated patients reported side effects and 8% dropped out because of them. In the Hypericum group, 20% reported adverse effects and 4% dropped out.

As noted in the Ernst review, most of the research and treatment experience with Hypericum comes from Germany. Dr Linde's group points out that unpublished trials and multiple publications by the same group could lead to an artificially inflated number of subjects who appear to have participated in published trials. They also express concerns that different preparations of the herb could contain other chemicals with pharmacologic properties.

In an accompanying editorial, de Smet and Nolen note that the initial monograph in 1984 on St John's wort identified hypericin as an experimental monoamine oxidase inhibitor. (3) The clinical relevance of this claim has not been confirmed, according to these editorialists, and hypericin may not be the only bioactive constituent of the herb. On the positive side, extensive use in Germany has not resulted in published case reports about serious drug interactions or toxicity after overdose. In an open study of 3250 patients, the most common side effects were gastrointestinal disturbances (0.6% ), allergic reactions (0.5%), and fatigue (0.4%). Linde et al mention reports of phototoxicity in animals taking high doses of Hypericum and observe the absence of data about St John's wort's long-term safety.

The fact that a product is natural does not mean that it is either safe or efficacious. By the same token, there is no reason why an herb or other plant product cannot have healing powers. Medicine is an empirical science, and while some purported remedies have turned out to be ineffective or even hazardous when subjected to systematic study, others have stood the test of time and science. St John's wort has now come to clinical and public attention, and preliminary results warrant larger trials. Studies of Hypericum in patients testing positive for the human immunodeficiency virus are also generating promising results in preventing the development of the acquired immune deficiency syndrome. Calls to health food stores in the Tucson area revealed that St John's wort is widely available and costs about $10 to $14 for one hundred 375-mg capsules. As we noted in a recent discussion on melatonin (BTP 1996; 19: 4), there is a lack of sufficient data on safety (particularly long-term), efficacy, potential interactions, and product purity of products sold as nutritional supplements rather than as drugs, such as St John's wort. Therefore, we recommend against its use for now.

1. Ernst E: St. John's wort, an anti-depressant? A systematic, criteria-based review. Phytomedicine 1995; 2: 67-71.
2. Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D: St John's wort for depression -- An overview and meta-analysis of randomised clinical trials. BMJ 1996; 313: 253-258.
3. de Smet PAGM, Nolen WA: St. John's wort as an antidepressant. BMJ 1996; 313: 241-242.

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Original article copyright 1997 Biological Therapies in Psychiatry.
Web page copyright 1998 Robert Hsiung.