Reviewed: Fugh-Berman A, Ernst E. Herb-drug interactions: Review and assessment of report reliability. British Journal of Clinical Pharmacology 2001;52:587-95.

This article assesses the published clinical literature regarding interactions between conventional drugs and herbal medicinal products. While many, though not all, drug-drug interactions are well defined, the authors state that herb-drug interactions may occur more frequently due to the many pharmacologically active compounds present in most herbal products.

A search of Medline, Embase, the Cochrane Library, and CISCOM (a database specializing in alternative medicine literature) from their inception to 2000 was conducted using the search terms "herbal medicine," "botanical medicine," "phytotherapy," "adverse-effects," "side effects," and "drug interactions." Ten major herbal product manufacturers were asked for data on interactions; eight experts and 24 organizations were asked for further information. Four major reference texts, six recent review articles (since 1993), the authors' files, and the bibliographies of all articles used were also searched.

A 10-point scoring system assessed interaction probability. The scoring system, while not validated, helped to determine whether reports of herb-drug interactions contained reliable information. Reports received one point for each of the following:

� Adequate patient history

� Concurrent diseases, conditions, or medications presumably are not associated with the adverse event [The original article contained a misprint stating that "...medications associated with an adverse event"]

� Documentation of concomitant medications

� Adequate description of interactors

� Exclusion of obvious alternative explanations

� Complete chronology

� Reasonable time sequence of drug administration to adverse event

� Adequate description of adverse event

� Cessation of event on stopping the drug

� Recurrence of event with rechallenge [with the suspected interacting herb-drug]

A score of 0�3 was considered unevaluable, 4�7 implied some evidence for an interaction (possible), and 8�10 indicated a well-documented report with reliable evidence for interaction (likely).

The search of all listed sources produced 108 cases of suspected interactions, which were tabulated in the article and categorized by patient description, herb, drug, other medications, signs or symptoms of interaction, mechanism, and report reliability score. Seventy-four cases (68.5 percent) were considered to contain insufficient information to evaluate (unevaluable), 14 (13 percent) were classified as well-documented (likely), and 20 (18.5 percent) as possible.

The authors review published herb-drug interactions. From these clinical studies and the case reports, they surmise that enough cases of interactions with SSRIs have been reported that a serotonin-amplifying effect of St. John's wort (Hypericum perforatum L., Clusiaceae) could occur. Patients taking St. John's wort or anticoagulants are at the highest risk of an herb-drug interaction. They further advise monitoring patients who take ginkgo (Ginkgo biloba L., Ginkgoaceae), garlic (Allium sativum L., Alliaceae), Chinese salvia or dan shen (Salvia miltiorrhiza Bunge, Laniaceae) or other herbs that affect platelet function for possible interactions with anticoagulant drugs.

Although the authors state that even well-documented case reports can only serve as an early warning system, they urge those who publish case reports to document all relevant information, including known biochemical interactions. Case reports should clearly describe the adverse event, explore alternative explanations, and document a rechallenge when possible. Herbal products should be analyzed to confirm their content.

This article presents its information in a coherent, usable form, and the discussion provides in-depth analysis of the biochemical bases for herb-drug interactions. The summary table provides an opportunity to judge the merits of the scoring system and is a valuable source of information to enhance awareness of possible interactions. [This table was excerpted for HerbClip to show the 14 cases considered to be likely herb-drug interactions, based on the well-documented reliability of the reports. It is available in the sample HerbClip section on ABC's website, <www.herbalgram.org>.] The excellent bibliography highlights the breadth and depth, as well as the credibility, of the work described in the article.

-Diane S. Graves, M.P.H., R.D.