With the popularity of herbs, botanicals and other natural remedies continuing to explode, a unique web-based resource recently launched by Memorial Sloan-Kettering Cancer Center will help fill the information gap for both medical practitioners and the general public.

The web resource includes monographs on 135 agents, providing clinical summaries of each, as well as the purported uses, mechanisms of action, adverse reactions, drug interactions and links to scientific research and critiques. The website provides invaluable information for physicians that is comprehensive and current, and will be continually updated by the Chief of Integrative Medicine at MSKCC and a pharmacist and botanicals expert. Discover what you don't know at: http://www.mskcc.org/aboutherbs.

As patients become more involved in their own health care and investigate the use of alternative medicines, it is ever more important to fully characterize the nature of these medicines. One such substance is St. John's Wort (Hypericum perforatum), regularly taken to treat depression. What remains to be established is whether or not St. John's Wort actually works. Results of studies have run the gamut from superior to placebo, to equivalent to other antidepressants to indistinguishable from placebo.

A recent study investigated the effects of hypericum on patients with well-defined major depression of moderate severity, and included a four-month continuation phase and sertraline as an active comparator. The trial was a randomized, double-blind, parallel-group eight week outpatient trial of hypericum, sertraline or placebo, followed by up to 18 weeks of double-blind continuation. The main outcome measures were changes in the Hamilton Depression scale (HAM-D) total score from baseline to eight weeks, and rates of full response, determined by the HAM-D and Clinical Global Impressions (CGI) scores.

Results were disappointing and somewhat unexpected. Not only could hypericum not be differentiated from placebo, neither could sertraline. Although the efficacy of sertraline was demonstrated on the secondary CGI-I measure, hypericum had no efficacy on any measure.

The study authors suggest a number of reasons for their results. The hypericum used in the trial was not standardized to hyperforin, which is possibly an important active ingredient. Also, it is possible that hypericum may be most effective in less severe major depression. The authors also conclude that perhaps the study lacked appropriate sensitivity. They suggest that this study outlines the importance of including an active comparator drug in a study. Without sertraline as an active comparator, the results would have been interpreted as evidence for a lack of efficacy of hypericum, without consideration of the possibility that a low assay sensitivity of the trial might have contributed to the finding.

Source

1. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St. John's wort) in Major Depressive Disorder. JAMA 2002; 287:1807-1814.

Potential Herb-Drug Interactions in Older People

Julie Dergal, MSc
Kunin-Lunenfeld Applied Research Unit,
Baycrest Centre for Geriatric Care,
Toronto, ON.

Paula A. Rochon, MD, MPH, FRCPC
Baycrest Centre for Geriatric Care,
Assistant Professor of Medicine,
University of Toronto, Toronto, ON.

Introduction
The use of herbal medicines has recently gained a great deal of acceptance in North America. In 1996 in the United States, an estimated two billion dollars was spent on herbs, tablets, extracts, capsules, and teas, in health food stores.¹ In 1997, Eisenberg conducted a telephone survey of 2055 people and found that 12% used herbal medicines, a 4-fold increase from 1991.² Despite the widespread use of herbal medicines in North America, little research has examined the safety of these alternative medicines, particularly when taken in conjunction with conventional medicines. A common misconception about alternative medicines is that they are "natural" and are, therefore, safe. However, herbal medicines are marketed as dietary supplements and, as such, are not subject to the rigorous standards established for conventional drug therapies. This means that the quality and content of herbal medicines are largely unregulated and uncontrolled.

Jerry Cott, PhD
Research Pharmacologist,
Scientific Advisor to the Health Professions,
College Park, MD.

St. John's Wort (Hypericum perforatum; SJW) is a common roadside plant that has gained much popularity in Europe and the United States as an alternative to synthetic antidepressants. The market for SJW in 1998 was $330 million in Europe and $210 million in the U.S. Hypericum appears to be an effective antidepressant with an excellent safety profile (with the interaction caveat discussed here). The NIH has just completed a multi-centre study comparing the efficacy of SJW to sertraline and placebo for treating patients with moderate to severe depression. This study was completed in December 2000, and results should be available in the summer of 2001.

Although SJW has been shown to inhibit monoamine oxidase (MAO) in vitro, this effect has not been demonstrated in vivo, nor have there been any reported cases of MAOI-associated hypertensive crises in humans using SJW.¹ Although SJW has been reported to inhibit uptake of serotonin, norepinephrine and dopamine in vitro,² the concentrations required to attain these effects are quite high and the chance of a patient attaining equivalent blood concentrations is low. In fact, a recent study suggests that the uptake inhibition is only an artifact of the assay since, in contrast to other inhibitors, it does not bind to the serotonin uptake site but does deplete storage vesicles in a similar fashion to reserpine.