St. John's What?

When you squeeze the bright star-shaped yellow buds of the hardy perennial Hypericum perforatum, they yield a red juice that reminded medieval Europeans of the blood of John the Baptist. Valued for its magical healing powers, St. John's wort (a Middle English word for "plant"), as the shrub is commonly called, has been used since the time of ancient Greece for treating any number of ailments, from liver and bowel disorders to hysteria, obesity and insomnia.

But St. John's wort came into its own in 1984, when the German government classified it as an MAO inhibitor, on the basis of in-vitro studies, and approved its use as a mild, natural antidepressant. Sales took off both in Germany, where St. John's wort easily outsells prescription drugs like Prozac, and in the U.S., where concoctions of the herb, sold under such labels as Mood Support and Brighten Up, became flagships of the booming alternative- medicine industry. Before last year's warnings that St. John's wort could interfere with other medications--notably AIDS treatments, antibiotics, cardiac drugs and oral contraceptives--yearly sales had reached $310 million. Even today, some 1.5 million Americans take the extract regularly to treat their psychic pain.

Let's hope they're doing something else to make themselves feel better, because the bloom may just have come off this flower. In what is by far the most definitive study yet of the efficacy of St. John's wort in treating major depression, doctors last week concluded that the extract is essentially useless. On the basis of these findings, published in the Journal of the American Medical Association, Dr. Richard Shelton, a psychiatrist at Vanderbilt University and the study's lead author, says flatly that he wouldn't recommend St. John's wort to any of his patients. As for the 30 or so earlier trials showing that the herb had some therapeutic value, he--like many other scientists--dismisses them as badly designed, inadequate or otherwise flawed.

Coming as it did amid reports that federal regulators are about to call for tighter controls on dietary supplements, including the memory pill Ginkgo biloba (which has been found to cause excessive bleeding and, in rare cases, stroke), the study's conclusions touched a raw nerve among those who see herbal medicine as a gentler, more natural route to healing. The nonprofit American Botanical Council issued a stinging press release criticizing the research as inconclusive, and the supplement industry's Council for Responsible Nutrition said there was nothing in the study that showed St. John's wort wouldn't work in cases of mild to moderate depression. Says the group's president, John Cordaro: "Consumers wouldn't use a throat lozenge for strep throat, but that same lozenge might be just right for a scratchy throat."

Shelton, however, stood his ground. He organized the study after seriously depressed patients, who had taken St. John's wort but hadn't been helped by it, began turning up en masse at his office. Learning that other psychiatrists were encountering a similar influx, he recruited doctors at nearly a dozen medical centers to join him in a clinical trial of the effectiveness of St. John's wort in combatting depression. With unrestricted funding from Pfizer, which makes both the prescription antidepressant Zoloft and an extract of St. John's wort, the doctors recruited 200 subjects, nearly two-thirds of them women in their 40s. All had suffered from major depression for at least four weeks. Some found it difficult to get out of bed or care for their children.

Blindly assigned to one of two groups, they were given either a placebo or St. John's wort. The initial dose: three standard 300-mg tablets a day, which was upped to four tablets if there was no improvement after four weeks. Although the St. John's wort group showed slightly more improvement than the placebo group (27% v. 19%) at the end of the eight-week trial, the doctors regarded the difference as statistically insignificant. When taking prescription antidepressants, two-thirds of patients improve.

Shelton and his colleagues acknowledge that theirs is not the final word. That could come before the end of the year when the National Institutes of Health completes a larger, three-year study that will meet one of the criticisms of the Vanderbilt trial. Instead of simply dividing patients into two groups--one on St. John's wort, the other on a placebo--the NIH study has a third group taking a prescription antidepressant. What should people who are using St. John's wort or thinking about it do until then? "Hold off," says Shelton, and consider one of the nearly two dozen prescription medications whose effectiveness has been proved.