Herbs for nerves.

Goodbye Prozac. Hello St. John's wort. Prescription drugs can be expensive and have side effects. Herbs are often cheaper ... and they're "natural." If you're feeling a little stressed, anxious, or depressed, what's wrong with leaning on them to help you make it through the day? Maybe nothing. Maybe something:

* While studies of mood-altering herbs like St. John's wort and kava look promising, researchers have focused on people who suffer from clinical depression or anxiety--not those who say they just feel "blue" or "edgy."

* If you have clinical depression or anxiety, popping pills shouldn't substitute for seeking professional help.

* Research into drugs and the mind is notoriously difficult to do. People often improve as much when they take a (inactive) placebo as when they take a drug or herb.

* Herbs are rarely tested to see if they cause cancer, birth defects, kidney or liver toxicity, fertility troubles, or other long-term safety problems.

* Herbs are not as carefully manufactured as drugs. You may or may not get the potency that's listed on the label.

Here's what you need to know about the two most popular mood-altering herbs.

St. John's Wort

St. John's wort blooms in June, around the traditional date of the saint's birth. Hence its name ("wort" is an old Anglo-Saxon term for "plant").

But the herb didn't really blossom until the mid-1990s, when it catapulted from an obscure folk treatment for wounds and "melancholy" to a trendy street-legal antidepressant ... and the hottest supplement since ginkgo.

The trigger? A 1996 "meta-analysis" in the prestigious British Medical Journal that pooled the results of more than a dozen European studies on St. John's wort in people suffering mild to moderate clinical depression.(1)

Clinical depression is more than just feeling "depressed" or "down." Among the symptoms, which can persist for months or years: feelings of worthlessness and hopelessness; loss of interest in activities that were once enjoyed; sleep disturbances; thoughts of suicide; difficulty concentrating or remembering; loss of appetite or overeating; and persistent physical symptoms--like headaches, digestive disorders, and chronic pain--that don't respond to treatment.

Most of the pooled studies in the meta-analysis tracked their participants' state of mind using the Hamilton Depression Scale (HDS), which measures day-to-day symptoms of depression like guilt, suicidal thoughts, irregular sleep, and weight changes. It's the same gauge that's typically used to test new prescription drugs for depression.

The meta-analysis made headlines: The 408 people taking St. John's wort were nearly three times as likely to show improvement as the 420 people taking a (lookalike but wort-free) placebo.

The studies in the meta-analysis were "reasonably well done," says Jacques Bradwejn, Chief of Psychiatry at the Royal Ottawa Hospital in Canada. "But they're not comparable in quality to the kinds of studies necessary to have a new antidepressant drug approved." Some unanswered questions:

* How long? The studies lasted only an average of five weeks. The longest was two months. "Many people suffer from chronic depression and need to take medication for months and years," says Bradwejn. "The studies done so far don't show for how long St. John's wort works or for how long people need to take it."

* How many helped? About half the people on St. John's wort did better than those on the placebo. But that means about half didn't.

* How depressed? None of the studies looked at whether St. John's wort helped people with severe depression or people with clinical depression plus clinical anxiety.

* How much? In some of the studies, the volunteers were given five times more St. John's wort than in others. The meta-analysis didn't try to figure out how much of which brands worked ... or didn't work.

Three additional studies in the meta-analysis pitted St. John's wort against prescription antidepressants for four to six weeks. Sixty-four percent of the herb-takers improved, compared to 58 percent of the drug-takers. Statistically, that's a tie.

"These studies only used low doses of the older tricyclic antidepressants like Toframil, not the new generation of selective serotonin reuptake inhibitors like Prozac or Zoloft," points out Bradwejn. "So we don't know how well St. John's wort compares with them."

Even so, the humble herb looks pretty impressive. And it looks even better when you consider that volunteers who took St. John's wort reported no more side effects than people who got the placebos. What's more, they were less than half as likely to report side effects as those who took the antidepressant drugs.

Some St. John's won-takers complained of dizziness, gastrointestinal upset, increased sensitivity to sunlight, fatigue, and confusion. "But these problems were usually mild," says Jerry Cott, chief of the Adult Psychopharmacology Research Program at the National Institute of Mental Health in Rockville, Maryland.

So why not take St. John's wort on your own if you think you're depressed?

Long-term safety is always a question with herbs, of course. Traditionally, St. John's wort was not used every day for long periods of time. What's more, relying on St. John's wort alone could delay you from getting the help you really need.

"People can self-diagnose their problems incorrectly and not realize that they suffer from something that would benefit from other kinds of therapy rather than from a pill," says Bradwejn. "Plus, they don't always remember how well they should feel and when to stop taking medication or when to keep taking it."

"People who suffer from depression frequently become isolated from others," says Soo Borson, director of Geropsychiatry Services at the University Of Washington Medical Center in Seattle. "Effective treatment includes help in reconnecting with others. Going into the cupboard for St. John's wort to treat one's depression by oneself may be counterproductive."

Bradwejn's advice: "Someone whose depression is not too intense might try St. John's wort with the aid of a psychologist or psychiatrist. Like prescription antidepressants, it takes a minimum of four weeks to kick in, so set a goal of eight weeks for the relief of symptoms. If it hasn't worked by then, try something else."

Beating the Blues

Try to find the word "depression" on any bottle or advertisement for St. John's wort. Why isn't it there? A dietary supplement company that uses the "d" word risks getting its product confiscated by the Food and Drug Administration (FDA) for even suggesting that it can prevent or treat a disease.

That's why all you'll see are vague invitations to try St. John's wort if you want to "beat the blues" (Prosol Plus), if you "feel like life has let you down" (HyperiCalm), or if you need something to help "maintain emotional balance and well-being" (Kira).

While those claims are legal (don't call us; it's Congress's fault), they're not based on any scientific studies. No one's ever looked to see if St. John's wort can help people who aren't suffering from clinical depression "shake the blues" or get "back on track."

Down the Pipe

This fall, St. John's wort will be the subject of the first major federally funded study of an herbal supplement.

The trial, which is being sponsored by the National Institute of Mental Health, will pit the Kira brand against both a placebo and a popular antidepressant for eight weeks in 336 patients suffering from moderate to severe depression. People who respond to St. John's wort will be followed up for an additional four months. Kira is the brand most often used in the successful European studies. It's made by Lichtwer Pharma, which also makes the popular Kwai brand garlic supplement.

"This new trial will bring the study of St. John's wort up to standard and put it on more solid scientific ground," says Bradwejn, who helped design the study. "And it will develop a better profile of possible side effects."

(1) British Medical Journal 313: 253, 1996.

The Bottom Line

* St. John's wort appears to help about half of those with mild to moderate depression. No good research has looked at whether it's useful in treating severe depression or whether it can "chase the blues away" or "smooth out little ups and downs."

* There are no studies on the long-term safety of taking St. John's wort. Short-term side effects seem to be mild, though it can cause an inflammation of the skin. "While this seldom happens with normal doses," says botanicals expert Varro Tyler, "those who take the herb for extended periods should be aware of the possibility and discontinue usage if it occurs."

* Researchers have little information about St. John's wort's possible interactions with other drugs.

Kava

On special occasions, people living in the South Pacific serve a mood-altering beverage brewed from the ground-up roots of the kava kava tree, just as they've done for thousands of years.

"Its ritual use as a mild sedative to produce a state of well-being has been described by numerous anthropologists, including Margaret Mead," says Mark Blumenthal of the American Botanical Council in Austin, Texas.

Save your airfare. This year's "herbal superstar" (The Wall Street Journal) is as close as your local supermarket or health food store. Who can resist an invitation like the one from Kavatrol, the most widely advertised brand: "Move to another state ... a calmer state"?

Can kava help bring relief from the stresses and annoyances of daily life? Only one bit of research suggests that it might: an unpublished study released on the World Wide Web (by the makers of Kavatrol).

Anxiety

Five published studies, all conducted in Europe, have compared kava with (lookalike but kava-free) placebos in several hundred people with mild to moderate clinical anxiety.(1-5) That's far more than occasionally feeling nervous or tense. According to the National Institute of Mental Health, "an anxiety disorder may make you feel anxious most of the time, without any apparent reason. Or the anxious feelings may be so uncomfortable that, to avoid them, you may stop some everyday activities."

Most of the people in the studies had been diagnosed with at least one anxiety disorder such as agoraphobia--a fear of having panic attacks in public places.

Researchers tracked how well they did on the kava or placebo using the Hamilton Anxiety Rating Scale (HAM-A), a standard tool used in testing anti-anxiety drugs. It measures how much a person anticipates the worst, feels tense, is fearful, has difficulty sleeping and concentrating, and suffers an array of other mental and physical problems. Normal scores are 17 or less, while 25 indicates a state of mild anxiety and 30 a state of moderate anxiety.

The studies used 300 to 400 mg of kava extracts a day (they contained 210 to 240 mg of kavalactones, which many researchers think are kava's active ingredients). Four of the studies lasted four to eight weeks, the fifth one lasted 24 weeks.

In each, the kava-takers showed significant relief of their symptoms compared with the placebo-takers.

In the longest, conducted in 1997 at Jena University in Germany, the average HAM-A scores of the 52 men and women taking kava dropped from 31 to 10 after 24 weeks, while the scores of those taking the placebo dropped to 15.(5)

And, when the study ended, the participants showed no signs of dependency, unlike what often happens with prescription tranquilizers like Xanax.

But the study suffered from the same problem that muddies much of the research into drugs and mental state--taking anything often makes people feel better. While three-quarters of the volunteers reported significant improvement when taking kava, so did half of those who took the (inactive) placebo. And at the conclusion of the study, nearly everyone--no matter what they took--reported feeling better than when the study began.

What's more, "these few kava studies are limited because they didn't rigorously control who participated in them," says the National Institute of Mental Health's Benedetto Vitiello. "So it's not really clear what the participants were suffering from--whether it was just tension, fluctuating anxiety, or a true psychiatric problem."

Stress

Most of us don't suffer from clinical anxiety. But we do have to cope with the hassles and annoyances of daily life. Can kava help?

Only one study has looked. Its details--they haven't been reviewed or published in a scientific journal yet--were released on the World Wide Web last April by the makers of Kavatrol, which was used in the research (www.natrol.com).

"We looked at the effect of kava on the kind of stress you might suffer if your mother-in-law were coming to visit and the two of you didn't get along," says the study's principal investigator, Nirbhay Singh of Virginia Commonwealth University in Richmond.

Singh used the Daily Stress Inventory, which tracks the impact of relatively minor daily events that are perceived as stressful, annoying, or unpleasant--like being stared at, having car trouble, or arguing with a spouse or mate.

"Kavatrol relieved this kind of stress within a week and continued to work during the four weeks we studied it in 29 people who were suffering more than an average amount of stress," says Singh, who became familiar with kava in his native Fiji.

The 31 other over-stressed people who received a placebo found no relief, says Singh, who adds that he has submitted his research for publication in a scientific journal.

Kava Caveats

"The more appropriate place for kava is if you're about to be prescribed a tranquilizer to treat your mild or moderate anxiety," says Jerry Cott of the National Institute of Mental Health.

"You might discuss with your doctor trying kava first because it seems to work for some people and doesn't have the problems of dependence that most conventional anti-anxiety drugs do."

If you take kava, here are three things to watch out for:

* Alcohol. "Kava may increase the effects of alcohol, so kava users shouldn't drink alcoholic beverages," advises Steven Dentali, a natural products pharmacologist who has reviewed the evidence on kava's safety for the herb industry. Some labels (Kavatrol, Soloray, and Nature's Way, for example) carry a warning about alcohol. Others (like Country Life) don't.

* Drug interactions. "Kava may also interact with prescription medications," cautions Dentali. In 1996, a Georgia man slipped in and out of consciousness a week after he began taking kava to wean himself off Xanax. His doctors blamed it on the kava-Xanax combination.(6)

"The impact of kava on prescription drugs is the big, serious unknown about this herb," concedes Gary Friedman, who heads the Kava Committee, a consortium of kavaselling companies.

* Safety. Like most other dietary supplements, kava has not been tested to see if it causes cancer, birth defects, or other long-term safety problems.

(1) Pharmacopsychiatry 22: 258,1989.

(2) Fortschr. Med. 108: 49, 1990.

(3) Fortschr. Med. 109: 119, 1991.

(4) Phytomedicine 3: 113, 1996.

(5) Pharmacopsychiatry 30: 1, 1997.

(6) Ann. Intern. Med. 125: 940, 1996.

The Bottom Line

* Kava seems to relieve some of the symptoms of clinical anxiety. According to a new unpublished study, it also relieves some of the stress of ordinary living.

* There are no studies on the long-term safety of taking kava every day.

* If you take kava, don't drink alcoholic beverages. If you take prescription drugs, check with your doctor before taking kava.

* Don't take kava if you're under 18, are pregnant or nursing, or plan to operate heavy equipment, cautions the National Nutritional Foods Association, a health food and dietary supplement industry trade group.