SAN FRANCISCO (San Francisco Chronicle) -- St. John's wort, a popular herbal supplement touted as a remedy for depression, did no better than dummy pills in a long-awaited government-backed study, doctors report Wednesday.

The findings cast doubt on marketing-fueled folk wisdom that has helped turn extracts of a short, yellow-flowering weed, formally known as Hypericum perforatum, into a consumer-health phenomenon with $180 million in sales in 2000.

The new study was one of the most ambitious attempts yet to apply the exacting standards of mainstream medical research to evaluate an herbal health product.

"We gave St. John's wort a pretty good try," said Dr. Jonathan Davidson, lead author of the study, which appears Wednesday in the Journal of the American Medical Association.

St. John's wort, whose medical uses date back to the ancient Greeks, may help against some milder forms of depression, Davidson said, but in more serious cases the herb "has not earned its membership yet in the club" of proven antidepressants.

Hypericum extracts are ranked among the top five best-selling dietary supplements in the country.

It's typically taken without a doctor's advice to alleviate the symptoms of depression, a condition affecting 9.9 million American adults per year, according to federal health experts. Nearly a quarter of the population is said to encounter at least one major depressive episode during his or her lifetime.

Herbal product makers criticized the new study, saying researchers looked at the wrong kind of patients.

"It is inexplicable that JAMA has created such fanfare over the fact that St. John's wort is not shown to be effective for a condition that it was never intended to treat," said Steven Dentali, vice president of scientific and technical affairs for the American Herbal Products Association, in a news release Tuesday.

Several smaller studies, mostly from Europe, have shown the herb can produce a benefit in cases of mild depression. There is also some evidence suggesting the herb has at least weak effects in the brain similar to those of widely prescribed prescription remedies.

The new study is the first large study to evaluate St. John's wort against both a placebo and an established antidepressant.

Researchers at Stanford University and 11 other leading medical centers around the country enrolled 340 study participants, all outpatients meeting strict diagnostic criteria for "moderately severe major depression."

Some patients received capsules containing a standard dose of St. John's wort, while others got a similar-looking pill, either an inactive placebo or Pfizer Inc.'s Zoloft (sertraline). Participants were tracked for eight weeks. Those who responded to whatever they were taking were followed for up to an additional 18 weeks.

Overall, neither the herb nor the drug performed clearly better than the well-known "placebo effect" - a potent factor in treating cases of depression, where symptoms may ease to some degree by mere contact with the medical system.

Zoloft did bring more relief than the fake pills on some measures, and doctors deliberately kept dosages low in order to minimize risk of side effects. As for St. John's wort, however, the researchers found a "complete absence of trends suggestive of efficacy."

"St. John's wort didn't work," said Dr. Alan F. Schatzberg, a Stanford psychiatrist who participated in the trial. "For anybody with serious depression, it's not a good idea."

The study was financed by the National Institutes of Health, and it was the first study of its kind to be sponsored by the NIH's National Center for Complementary and Alternative Medicine.

"In science, we are always hesitant to call any study "definitive,' but this one comes pretty darned close," said Patrick Finley, assistant professor of pharmacology at the University of California at San Francisco.

Results are generally in line with those of another large study last year, also published in JAMA and led by Dr. Richard Shelton at Vanderbilt University.

"The kind of patients studied was very similar in both studies," Shelton said Tuesday. "These are folks who typically would be treated with an antidepressant in a physician's office somewhere. The take-home message is that St. John's wort doesn't work in those people."

Doctors also warned that the herb can be dangerous. Side effects, though typically minor, can include nausea, headaches and an increased susceptibility to sunburn. It can also interact unpredictably with other drugs, including cancer therapies, and can reduce the effectiveness of birth control pills. Potency and purity can vary depending on the manufacturer.

Physicians used to treating depression said people self-medicating with St. John's wort should advise their doctor and be alert to any side effects. But they also said there's no overwhelming reason to stop taking the herb if it seems to be helping.

Other than the expense and potential side effects of self-medicating, doctors said people suffering serious bouts of depression may be missing out on more effective treatment options than St. John's wort.

"For some people, it's not unreasonable to give it a try," said Dr. Ellen Haller, a UCSF psychiatrist. "But just because it's an herb doesn't mean it's safe."

Copyright 2002 The San Francisco Chronicle. All rights reserved.