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Am Fam Physician. 2001;63(5):971-973

The treatment of “demonic possession” with Hypericum perforatum (St. John's wort extract) has been common in Europe since ancient times and is described by Hippocrates, Pliny and Galen. Hypericum extracts are licensed in continental Europe and are available over-the-counter in the United Kingdom for the treatment of depression and anxiety. Results from 23 trials have been published comparing different forms and doses of hypericum with conventional treatment for a variety of psychologic conditions. However, many of these studies have been criticized because of methodologic flaws. Woelk and colleagues conducted a randomized, multicenter, double-blind, parallel-group trial comparing the efficacy and tolerability of hypericum extract with the recommended dosage of imipramine, one of the most commonly used tricyclic antidepressants, in the treatment of persons with mild to moderate depression.

From June 1997 to April 1998, adults attending 40 outpatient clinics in Germany were recruited for the study if they met clinical criteria for mild to moderate depression without suicidal ideation and scored 18 or more on the Hamilton depression scale on two consecutive visits. Participants with bipolar conditions or thyroid disease, and those who were pregnant, breast-feeding or premenopausal and not using a form of contraception, were excluded from the study. Participants were assessed using the 17-item Hamilton scale and global depression scales completed by participants and physicians, and a report of side effects. Of the 324 participants, 157 were randomly assigned to receive 250 mg of hypericum extract ZE 117 twice daily, and 167 were assigned to receive 75 mg of imipramine twice daily. At baseline, all participants were comparable in terms of demographic variables and degree of depression. Participants were treated for six weeks.

In the hypericum-treatment group, the mean Hamilton depression scores decreased from 22.4 to 12.0. This change was compared with the drop from 22.1 to 12.75 in the imipramine-treatment group. Comparable improvements were also recorded on the global impression scales. Only one subscale—the anxiety-somatization subscale of the Hamilton scale—showed a significant advantage for those in the hypericum group. Adverse events were reported by 63 percent of those in the imipramine-treatment group compared with 39 percent in the hypericum-treatment group. Sixteen percent of those in the imipramine-treatment group withdrew because of adverse effects compared with 3 percent in the hypericum-treatment group. The most common adverse events reported in the imipramine-treatment group included dry mouth (25 percent), sweating, dizziness, nausea, asthenia and headache. Dry mouth was also the most commonly reported adverse event in the hypericum-treatment group (8 percent).

Change in score on HDRSTreatment
Hypericum (n = 157)Imipramine (n = 167)Relative risk (95% CI)
50% decrease68 (43)67 (40)1.08 (0.83 to 1.40)
20% decrease115 (73)109 (65)1.12 (0.97 to 1.30)
10-point decrease77 (49)75 (45)1.09 (0.8 7 to 1.38)

The authors conclude that hypericum and imipramine were therapeutically equivalent during the six-week treatment period. Patient tolerance was better and the incidence of adverse effects less in the hypericum-treatment group. The authors suggest that hypericum be considered for first-line treatment in patients with mild to moderate depression, particularly in the primary care setting.

editor's note: This study appears to have been well designed, especially regarding blinding to reduce bias or placebo effects. Nevertheless, we must be cautious about using herbal remedies for serious illnesses like depression. The amount of active agent varies enormously among products, and many are mixed with other substances into “mental health” compounds. Those who find the evidence convincing and wish to treat patients with mild depression with St. John's wort should ensure that the dosage is therapeutic and that patients are aware of the U.S. Food and Drug Administration's view on the use of this medication.—a.d.w.

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