ON THE TRAIL OF THE FEEL-GOOD WEED; ST. JOHN'S WORT AN HERBAL OPTION TO ANTI-DEPRESSANTS.

Byline: Jane E. Brody The New York Times

The highly popular drug Prozac and its synthetic rivals may soon be in for competition in this country from a natural herb that grows prolifically on roadsides: St. John's wort.

The herb is already by far the favored therapy for treatment of mild to moderately severe depression in Germany, where it has been used therapeutically for centuries. In 1994, about 66 million daily doses of St. John's wort were prescribed by German doctors, who turn to other drugs only when the herbal remedy fails to work.

Most of the research on the herb, which is also used to treat other common physical and emotional disorders, has been conducted in Germany. Researchers there report that it is decidedly better than placebos in medical trials and at least as good as some prescription anti-depressants for treating the milder forms of depression.

It is also much cheaper and appears to cause far fewer side effects than commonly prescribed anti-depressants, making it a potentially preferable alternative to drugs like Prozac. While Prozac costs, on average, $80 a month, a regimen of St. John's wort costs about $10 a month. And unlike Prozac, which causes distressing side effects in about one-quarter of patients, the herb has been shown in studies to cause side effects in fewer than 10 percent of patients, and, in most cases, those side effects are reported to be mild.

But before you dump your Prozac, Paxil, Zoloft or other prescribed anti-depressant in favor of this increasingly popular herb, a more discriminating look at the evidence - pro and con - for the safety and effectiveness of St. John's wort is in order.

Named for a saint

St. John's wort (``wort'' is Old English for plant) is a weed also known as Hypericum perforatum. It was named for St. John the Baptist, whose birthday is celebrated on June 24, when the plant usually puts forth its yellow blooms.

Like other plants, it contains many different chemicals, which alone or in combination may account for its reputed therapeutic effects. Scientists do not yet know which substances in St. John's wort are responsible for its apparent anti-depressant activity or how they may act. Neither is it known why St. John's wort has been reported to have antiviral activity (researchers are currently investigating it as an adjunct to other AIDS drugs that suppress HIV production), as well as the ability to relieve menstrual discomfort and winter blues and to bolster immunity.

What they do know is that there is more to St. John's wort than hearsay and health-food-store claims. A review of 23 well-designed clinical trials published last summer in the British Medical Journal concluded, based on 15 placebo-controlled trials, that extracts of St. John's wort ``are more effective than placebo for the treatment of mild to moderately severe depressive disorders.''

The review also found evidence from eight other studies that St. John's wort may work as well as some other drugs in countering mild depression, but the research team, from Munich, Germany, and San Antonio, Texas, called for more exacting studies comparing the herb with standard anti-depressants like Prozac.

The researchers noted that the studies of St. John's wort involved relatively small numbers of patients and that the diagnosis of depression varied from study to study and did not always adhere to the stringent criteria used in the United States. Furthermore, the preparation (liquid extracts or capsules or tablets made from ground-up plants) differed from study to study, as did the medication's potency and dosages, and none of the trials lasted longer than eight weeks.

So while few short-term side effects were reported, the possible long-term hazards of St. John's wort remain unknown. Although no adverse effects have been detected in long-term users in Germany, only a long-term controlled clinical study can give the herb a clean bill of health.

Studies not required in U.S.

There is no requirement that such studies be done before the herb is sold in this country. Since it is sold as a dietary supplement, the Food and Drug Administration does not approve or disapprove it, and no documentation is required of its safety or usefulness, the kind of information required for prescription anti-depressants. Because it is classified as a dietary supplement, its label may not claim that it has a specific effect in alleviating depression.

There are side effects that have been associated with St. John's wort, including mild gastrointestinal discomfort (usually relieved by taking the medication with meals and a large glass of liquid), fatigue, dry mouth, dizziness, skin rashes and itching. Such side effects were reported by 2.4 percent of patients in one large study. At high doses, it may also increase sensitivity to sunlight, an effect that so far has been found only in cattle that graze heavily on it.

On the other hand, the prescription anti-depressants commonly cause distressing side effects like sexual dysfunction, diarrhea, difficulty with concentration, a decrease in reaction time, drowsiness and bad reactions to alcohol.

St. John's wort is not for everyone, and no one who is depressed should start taking it without first consulting a mental-health practitioner who is expert in diagnosing and treating depression. That is especially important for people who are severely depressed or suicidal, because St. John's wort may not be potent enough to counter severe depression. Also, even mild depression may require more than medication. Some form of psychotherapy often is needed to prevent relapses.

If you are now on a prescription anti-depressant, do not add St. John's wort to the regimen or abandon the prescribed drug in its favor. When combined with other serotonin-enhancing drugs, like Prozac, St. John's wort may result in a serotonin overload, causing sweating, agitation, confusion and tremor. See your doctor before making any chaSnges.

St. John's wort should not be used by pregnant or nursing women or young children because of the lack of safety information.

No checks on potency

Keep in mind that the FDA does not approve the preparations of St. John's wort on the shelves of health-food stores and pharmacies and that no agency checks these preparations for contents or potency. You are at the mercy of the manufacturer; the bottle may or may not contain what the label says.

As for dosages, that is also a guess. Dr. Jonathan Zuess, a doctor in Arizona who has studied herbalism and who wrote ``The Natural Prozac Program'' (Three Rivers Press, 1997, $10), favors the alcohol extract - about three-fourths of a teaspoon a day divided into two or three doses - that has been used in most of the German studies. If a capsule is chosen, look for brands containing 300 milligrams of the raw herb, standardized to contain 0.3 percent hypericin, one of the herb's most active ingredients. Take one capsule a day, less if you are older than 65. For further guidance on products, consult ``Hypericum & Depression'' by Dr. Harold Bloomfield, from Prelude Press, at [phone], now in paperback for $7.95.

You should also keep in mind that, like prescription anti-depressants, St. John's wort does not work right away. It takes about four weeks to have a significant anti-depressant effect, though you are likely to notice some improvement within two weeks. Since long-term safety studies are lacking, Zuess does not recommend the use of St. John's wort for more than a year.

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2 Photos

Photo: (1--Cover--Color) NATURAL HIGH

St. John's wort - the herbal alternative to Prozac?

(2) St. John's wort is an herbal remedy used by some as a treatment for depression, but it should never be used in conjunction with other prescribed anti-depressants.

David R. Crane/Daily News