The study is among the first to compare the supplement with a prescription antidepressant. It was funded by the German company that markets the St. John's Wort product used in the research, and was carried out by the company's researchers.

Some studies have shown that St. John's Wort might be useful in treating mild to moderate degrees of depression. However, prior studies have not shown it to be useful in the treatment of major depression.

The researchers treated 251 patients with major depression with either a standard dose of the St. John's Wort extract (900 milligrams a day) or the antidepressant Paxil (20 milligrams a day). Dosages of their treatment were increased in patients who did not show improvements. Neither the patients nor their physicians knew which treatment was being given.

At the end of six weeks, 71 percent of the patients taking St. John's Wort and 60 percent of those taking Paxil had responded to treatment. Half of the St. John's Wort-treated patients and 35 percent of the Paxil-treated patients were free of depression symptoms.

The findings are published in the latest online edition of the British Medical Journal.

Earlier Research

Millions of people take St. John's Wort to treat depression and related disorders. Until now studies have been lacking showing evidence of its effect in the treatment of major depression.

One of the most rigorous trials on the effects of the herbal supplement showed St. John's Wort to be no more effective for the treatment of major depression than a placebo. But the same was true for the prescription antidepressant Zoloft. That U.S. National Institutes of Health-sponsored trial was reported in the spring of 2002.

St. John's Wort researcher Kenneth Kobak, PhD, says the clinical evidence now seems to favor a role for the supplement in the treatment of moderate and even severe depression.

"I would like to see more evidence from rigorously designed trials before I am firmly convinced, though," he tells WebMD.

While St. John's Wort is generally considered safe when taken alone, many concerns have been raised in recent years about interactions with other medications. It has been shown to decrease the effectiveness of some lifesaving drugs, including those that fight cancer and AIDS, and drugs, such as cyclosporine, that prevent organ rejection after a transplant.

A study published in the fall of 2003 showed that taking the herbal supplement reduces the effectiveness of as many as half of all prescription and over-the-counter drugs.

Angelika Dienel, MD, who was a principal researcher for the German study, says the interaction concerns are valid. But she says St. John's Wort has a better overall safety profile than prescription antidepressants.

Drug-related adverse events were reported in 55 percent of the patients in her study taking St. John's Wort and in 76% of the patients taking Paxil. The most common side effects seen in people taking St. John's Wort were dry mouth, headache, and fatigue.

Dienel says St. John's Wort should be considered an initial treatment for patients with mild to moderate depression. But she adds that people with chronic depression should look to other treatments.

Kobak says anyone who does decide to try the supplement should definitely tell their doctor.

"I don't think there is a big risk to trying it, unless someone is severely depressed and they need immediate treatment that is more certain to be effective," he says.

By Salynn Boyles, reviewed by Brunilda Nazario, MD

SOURCES: Szegedi et al. British Journal of Medicine, online edition. Angelika Dienel, MD, head, clinical trials department, Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany. Kenneth Kobak, PhD, Dean Foundation for Health Research Education. WebMD Medical News: "Popular Supplements Scrutinized." WebMD Medical News: "St. John's Wort Affects Other Drugs."