St. John’s Wort (Hypericum perforatum) has been used in medicine for centuries. Pliny, Galen and Hippocrates all refer to its medicinal powers. While used for a variety of maladies during its long history, its most recent use is in the treatment of depression. St. John’s Wort is licensed in Germany for the treatment of anxiety, depression and sleep disorders and is available as an standardized extract. Over 2.7 million prescriptions were written by physicians in Germany for preparations of St. John’s Wort in 1993. This widespread acceptance in mainstream medicine in Germany is in marked contrast to its status in the United States as a nutritional supplement under the Dietary Supplement and Health Education Act. Despite its lack of compendial standing in the United States, St. John’s Wort enjoys widespread lay popularity.

Extracts of St. John’s Wort contain a number of biologically active constituents, including hypericins, flavonoids and bioflavonoids. Although German preparations approved by the Commission E are standardized to their content of hypericins, the mechanism by which St. John’s Wort exerts a pharmacologic effect is unknown. The standardization may not be a meaningful one pharmacologically. Extracts of hypericum show binding affinity for a variety of CNS neurotransmitter receptors including serotonergic and GABA receptors. St. John’s Wort may have MAO inhibitor properties as well.¹

Perhaps the most comprehensive literature review to date on the efficacy of St. John’s Wort in depression was published in 1996 by Linde and colleagues.² A total of 23 randomized clinical trials involving 1757 patients with depression ranging in severity from mild to moderately severe were evaluated. Fifteen of the trials were placebo-controlled and 8 compared St. John’s Wort to other drug therapies including maprotiline, imipramine, amitriptyline, desipramine, diazepam and bromazepam. The longest trial duration was 12 weeks of therapy in all of the studies examined. This meta-analysis suffers from many of the ills of its brethren. Only published data are available. The study populations were heterogeneous and the interventions were not standardized. The definitions used across the studies were not uniform. Unique to this meta-analysis is the problem of drug standardization. Multiple preparations or St. John’s Wort were employed in the examined studies and doses varied considerably. Hypericin doses ranged from 0.6mg to 2.7mg per day. Twenty of the 23 trials were double-blind trials. Despite these difficulties, the authors concluded that some depressive disorders were more successfully treated with hypericum than with placebo. Furthermore, they commented that hypericum may be as good an antidepressant as others, but there is still not enough evidence for this due to the small sample sizes in the studies.

Additionally, St. John’s Wort is not an innocuous compound. Since it has not been routinely demonstrated to be effective, patient self-diagnosis and self-treatment prevents adequate medical management. While St. John’s Wort appears to produce fewer side effects that traditional antidepressants such as imipramine and amitriptyline, photodermatitis, delayed hypersensitivity, GI upset, dizziness, dry mouth, sedation, restlessness and constipation have all been reported.¹

The NIMH, in collaboration with the NIH National Center for Complementary and Alternative Medicine and the NIH Office of Dietary Supplements, has begun the first large-scale US trial of St. John’s Wort in patients with depression. This 3-year multicenter study (including the MGH) will compare the efficacy of St. John’s Wort in a standardized preparation to placebo and to an SSRI. Until this NIMH study is completed, the relative role of St. John’s Wort in a standardized form in the management of depression is uncertain.

References:

1. Wong A, Smith M, Boon H. Herbal remedies in psychiatric practice. Arch Gen Psychiatry 1998;55(11):1033-1044.

2. Linde K, Ramirez G, Mulrow C, et al. St John’s wort for depression-an overview and meta-analysis of randomised clinical trials. BMJ 1996;313:253-258.