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4/16/2002

Efficacy of St. John's Wort Remains Uncertain

Kate Traynor

A $6 million National Institutes of Health study to determine whether an herbal extract can successfully treat moderate to severe depression seems to have produced inconclusive results.

For the most part, the researchers found no differences between the effects of placebo, which works in some depressed patients, and the study's two treatments: a standardized extract of St. John's wort, an herbal product that some people recognize as a treatment for mild depression; and sertraline, or Zoloft, an antidepressant marketed by Pfizer Inc.

After eight weeks of treatment, patients in the three groups had similarly better scores on the Hamilton Depression Scale, a common rating system for symptoms of depression.

Also, statistically indistinguishable proportions of patients—32 percent in the placebo group, 24 percent in the St. John's wort group, and 25 percent in the sertraline group—achieved a "full response" after eight weeks. The researchers defined a full response as a patient who, on the Clinical Global Impressions Scale, had a score indicating "much" or "very much" improved since the start of treatment. To be considered a full responder, a patient also needed to achieve a low score on the Hamilton Depression Scale after eight weeks of therapy.

The study findings were published in the April 10 Journal of the American Medical Association (JAMA).

Sertraline was included as an "active comparator" to confirm that the patient-assessment scales used by the researchers could distinguish between the response rates from St. John's wort and those from placebo. According to the drug product's labeling, sertraline has outperformed placebo in the treatment of major depressive disorder in at least two studies that measured changes in patients' scores on the Clinical Global Impressions and Hamilton Depression scales.

Despite the researchers' expectation that sertraline would be effective, the drug outperformed placebo in the current study on only one secondary outcome—the Clinical Global Impressions improvement score. With that result, the research team concluded that its assessment tools may not have been sensitive enough to detect real differences in treatment responses.

The research team recruited study participants from 12 academic or community clinics in the United States. Enrollment was restricted to nonsuicidal adults with a diagnosis of major depressive disorder.

After a week-long period of placebo use to confirm the diagnosis, study participants were randomly assigned to receive 900 mg/day of an extract of St. John's wort, or hypericum, standardized to contain between 0.12 and 0.28 percent hypericin; 50 mg/day of sertraline; or a placebo identical in appearance to the St. John's wort or sertraline product. The dosage could gradually be increased to a daily maximum of 1,500 mg of St. John's wort, 100 mg of sertraline, or an equivalent amount of the placebo tablets. In all, 72 percent of the patients took their assigned tablets for the full eight weeks.

The research team noted that the eight-week study's maximum daily dose of sertraline, 100 mg, was less than the "therapeutic range," 50–200 mg, observed in other studies of the drug. The labeling for sertraline states that the drug has been found effective for extended treatment of depression at dosages of 50–200 mg/day.

An editorial (PDF) in the same issue of JAMA emphasized the need to include both a placebo and an active comparator group in clinical trials of antidepressants.