Depressive disorders, with a 10 percent prevalence in the general patient population, are often underdiagnosed and undertreated. A review of clinical studies has shown hypericum extract (St. John's wort) to be more effective than placebo in the treatment of patients with mild to moderate depression. However, its effectiveness has been doubted because of methodologic problems in the studies and reports supporting its use—especially equivalence trials with other antidepressants. Philipp and colleagues conducted a multicenter, placebo-controlled, randomized, double-blind trial comparing the safety and efficacy of hypericum extract with imipramine and placebo in the treatment of patients with moderate depression.

Recruited for the study were 263 patients selected from cohorts of depressed patients by 18 general practitioners. Study participants were between 18 and 65 years of age and met ICD-10 criteria for moderate depression. Other inclusion criteria included depression of at least four weeks' duration. Participants also had to meet scoring minimums on the Hamilton depression rating scale and a clinical global impressions rating of severity. Exclusion criteria included bipolar disorder, suicidal risk, recent use of psychotropic medication and contraindications to imipramine therapy. After a screening period of one week (which included a washout period), patients were randomly assigned to one of three treatment groups. Patients were given hypericum extract in a dosage of 350 mg three times daily, imipramine in an initial dosage of 50 mg on the first treatment day followed by 75 mg on days 2 through 4, then 100 mg daily thereafter, or placebo. All drugs, including placebo, were identical and provided as one tablet three times daily. Patients were treated for eight weeks and reassessed using four standardized rating scales.

The three patient groups were comparable in age, sex and diagnosis of depression. Compliance was satisfactory in all treatment groups. After six and eight weeks of treatment, hypericum extract was more effective than placebo and comparable to imipramine in improvement of depressive symptoms in patients with moderate depression. Both drugs were more effective than placebo in improving quality of life in the mental component scale, but only hypericum extract was more effective in the physical component scale. Overall, adverse effects (chiefly dry mouth) were reported by 46 percent of patients taking imipramine. In the hypericum group, 22 percent of patients reported adverse effects (mainly nausea). One patient in the placebo group attempted suicide, and 19 percent of this group reported adverse effects.

The authors conclude that an average dosage of hypericum extract, 350 mg three times daily, appears to be as efficacious as imipramine in relieving moderate depressive symptoms. Although they found this regimen and formulation of hypericum to be effective, they caution that hypericum products are commercially available in a variety of dosages and compositions.