Although several smaller European studies have suggested that Saint John's wort is useful in treating mild to moderately severe depression, experts who reviewed those studies concluded that they had limitations and more rigorous trials were needed before firm
conclusions could be drawn. The current study was the first clinical trial of an alternative medicine therapy in the United States.

"Many Americans use dietary supplements like Saint John's wort for depression without consulting a physician," says principal investigator Jonathan R.T. Davidson, M.D. "We felt there was a need to conduct a trial that could help us determine where Saint John's wort fits in the overall management of depression."

"Our commitment is to apply exacting scientific methods to studying popular complementary and alternative medicine practices and to publish the results of such studies in critical peer-reviewed journals, so that the public and practitioners can make the most informed decisions about them," says Stephen E. Straus, M.D., of the National Institutes of Health (USA).

According to the National Institute of Mental Health, major depression affects approximately 9.9 million American adults age 18 years and older in a given
year and is a leading cause of disability in the United States.

"Major depression is a serious public health concern. Determining whether an herbal product, such as Saint John's wort, can work as a treatment is important," said Richard
K. Nakamura, Ph.D., Acting Director, National Institute of Mental Health. "We are always seeking treatment options to add to the list of proven medications and psychotherapies available to those suffering from depression."

Study participants' initial diagnosis and severity of depression were confirmed using three primary measures: the DSM-IV depression criteria, the Hamilton Depression Scale, and the Global Assessment of Functioning Scale. Participants who met manual criteria for major depression, who had initial Hamilton scores of 20 or higher, and who had at least moderately severe major depression according to the Functioning Scale, were recruited from 12 academic or community psychiatric research clinics across the country.

The study was conducted in two phases. The first 8-week phase, or acute phase, measured the number of people whose depression responded to treatment with St. John's wort (900 mg to 1500 mg per day), sertraline (50 mg to100 mg per day), or placebo; this phase was the primary focus of the study. A second, or continuation, phase offered
patients who had responded to their initial treatment another 18 weeks of therapy, which enabled researchers to gather data on longer-term use of the treatments. The preparation of Saint John's wort used in this study is one sold and produced in Europe and used in many earlier, smaller trials.

Two primary outcomes were measured during the first phase of the trial: improvements in Hamilton scores and Clinical Global Impressions- Improvement Scale score. The researchers found that Hamilton scores among patients taking Saint John's wort
dropped about 8.7 points on average versus approximately 9.2 points for placebo and 10.5 points for sertraline. They also found that approximately 24 percent of patients
taking the herb had full response to treatment versus about 32 percent for placebo and 25 percent for sertraline. The differences in these rates of response were not large enough to be statistically significant.

However, additional analyses showed that patients taking sertraline improved significantly more than those on placebo or Saint John's wort on the Global Impressions score, a secondary measure of improvement. In spite of this finding, the
overall response to sertraline on the primary measures was not superior to that of placebo, an outcome which is not uncommon in trials of approved antidepressants. In fact,
this apparent lack of efficacy occurs in up to 35 percent of trials of antidepressants.

"Overall, we found that patients taking either Saint John's wort or placebo had similar rates of response according to scales commonly used for measuring depression," says Dr.
Davidson. "And, although sertraline produced no greater effect than placebo on the primary measures, it fared better than placebo on the Clinical Global Impressions-
Improvement scale and produced results consistent with its known benefits."