Because many readers of The Medical Letter on Drugs and Therapeutics asked for an evaluation of St. John's wort, Medical Letter consultants responded with an early report based on current available data. St. John's wort is an herbal remedy derived from the flowering plant Hypericum perforatum and is widely available in health food stores. It is currently licensed in Germany for treatment of anxiety, depression and insomnia. At this time, it has not been evaluated by the U.S. Food and Drug Administration (FDA) and is considered a “dietary supplement.”

St. John's wort is an extract with many constituents. The primary one is hypericin, a naphthodianthrone. Although in Germany the dosage of the herb is based on its hypericin content, the actual amount of hypericin varies widely according to growth conditions of the plant. Hypericin inhibits the uptake of the neurotransmitters serotonin, norepinephrine and dopamine. It is not known if hypericin actually crosses the blood-brain barrier. Hypericin may also have some monoamine oxidase inhibitory capability. Following oral administration, serum concentrations reach a peak in about five hours and achieve steady state in about four days. Data on methods of metabolism and excretion are unavailable.

A meta-analysis of 23 randomized trials, published in the British Medical Journal (1,757 outpatients with mild or moderate depression) found hypericum extract to be superior to placebo and about as effective as standard antidepressants. The criticism of this particular analysis rests with the fact that the diagnosis of depression was not well established, the placebo response was lower than could be expected in similar studies, the standard dosage of antidepressants was low and the dosage of hypericum extract varied more than sixfold. The study interval also varied, from two to 12 weeks. To date, there have been no serious adverse effects reported with use of St. John's wort. Some patients have complained of dry mouth, dizziness, constipation and confusion. Overall, very few patients (less than 2 percent) discontinued therapy with the herb because of adverse effects. It has been reported that some grazing animals who have eaten the plant have suffered phototoxic reactions. A similar severe contact-phototoxicity reaction has been reported in a human.

Medical Letter consultants conclude that further well-conducted trials are needed before the effectiveness and safety of St. John's wort are established. Herbal remedies sold in the United States do not have FDA approval, and the active ingredients, and the potency and purity of these remedies are unknown.

edtor's note: Although some patients are already using herbal remedies, it is important to remember that many of these remedies have not been adequately studied in a way that will allow appropriate clinical decisions to be made. Practitioners should visit a modern health food store and survey the variety of compounds and remedies available to patients. The intense public interest in these products will perhaps generate well-conducted trials of their effectiveness and safety.