September 9, 1997
In Germany, Humble Herb is a Rival to Prozac
By EDMUND L. ANDREWSRANKFURT, Germany - It is a lush green plant with bright yellow flowers and a homely name: St. John's wort in English and Johanniskraut in German.
For centuries people in many countries used it to heal wounds and it found wide use in Germany as a tea that could soothe nerves and relieve melancholy.
Doctors studied it and wrote about it and some gave it to their patients. But with the rise of modern pharmaceuticals in the 20th century it fell into disuse.
Now, though, the ancient remedy has suddenly vaulted to international celebrity. A barrage of new clinical studies report that true to the folklore, St. John's wort provides measurable relief to people with mild and moderate depression without the side effects of drugs like Prozac, which currently dominates the roughly $6 billion worldwide market for antidepressants.
To be sure, pharmacologists caution that there are still important gaps in knowledge about the herb. There have yet to be any long-term clinical studies, so there is no information on the herb's effectiveness as a "maintenance" treatment.
Nor are there many data on the herb's effectiveness against severe depression, or on the ideal dosage levels. The herb also has at least one known side effect: a tendency to make skin more vulnerable to sunburn.
Nevertheless, here in Germany, where most of the new research has been conducted, high-strength preparations of St. John's wort have become by far the most popular antidepressants on the market. Available in grocery stores and pharmacies, the drug now outsells the nearest competitor, Prozac, by 4 to 1.
That, in turn, is fueling a surge of scientific interest worldwide, including in the United States. New clinical studies and articles on St. John's wort appear almost monthly. One book has been published in the United States this year and at least one more is on the way. People trade information about the herb on more than a dozen Web sites. And mainstream psychiatrists are beginning to recommend St. John's wort for patients who do not like the standard drugs.
Unlike common antidepressants, which can only be prescribed by doctors and must be tested for safety and efficacy before they are approved by the Food and Drug Administration, herbal remedies are not required to undergo such testing. Nor are makers allowed to claim specific medical benefits on the label. Nonetheless, doctors may recommend that their patients take herbal remedies.
"I started prescribing it about nine months ago, and I have had one success story after another," said Norman E. Rosenthal, a psychiatrist and clinical researcher in Rockville, Md., who is now writing a book on the herb. "It is an effective substance in a number of people."
The wide and growing use of the John's wort, Hypericum perforatum, has been a considerable surprise to mainstream medical doctors and pharmacologists, who have long been skeptical of herbal remedies. Indeed, it was only after more potent new preparations of the herb began to soar in popularity in Germany that many of the new clinical studies were even begun. The renaissance itself was driven by largely ordinary German patients, many of whom deeply distrusted synthetic drugs and demanded "natural" remedies.
"As pharmacologists, we are basically against herbal medicines because they are always a mixture of ingredients that can change from year to year, like good wine and bad wine," said Walter E. Mueller, head of the department of pharmacology at the University of Frankfurt and a leading clinical researcher on St. John's wort. "But the reality overcame us. Patients wanted to treat themselves with hypericum extract and we realized that we needed to understand it better."
One such patient is Edith Matzner, a 68-year-old retiree in the east German city of Chemnitz, who found herself falling into depression while her husband underwent cancer surgery four years ago. Like many Germans, she was reluctant to take conventional drugs, worrying about the effect of synthetic chemicals she did not understand. But then a trusted neighbor suggested that she try St. John's wort, and she began drinking tea made from it two or three times a day.
"The effect was clear after 10 days," Mrs. Matzner said. "The fear that everything good was disappearing stopped after 10 days, and I could look forward with a completely positive attitude and devote my strength to supporting my husband." Elke Baer-Rudolf, a cosmetician in Berlin, says she has been taking St. John's extract regularly for years to alleviate what had been persistent stress and anxiety. "My doctor once suggested that I take Valium, but I said no because I don't like to take synthetic drugs," she said. Her doctor then suggested the herbal preparation, which appealed to her. "It immediately reduces my restlessness and nervousness," she said.
Most people here take St. John's wort three times a day in the form of a high-strength pill that contains about 300 milligrams of extract. These pills, first introduced in 1992 by a small company in Berlin called Licht Wer Pharma, greatly increased the effects of the herb and set off a big jump in its use. Since 1992, sales of hypericum products in Germany have more than doubled to about $71 million this year. Hypericum's share of the German market for antidepressants climbed from 16.4 percent in 1992 to 27.3 percent in 1997, Licht Wer estimates.
Experts in both Germany and the United States say that Licht Wer played a central role in the rebirth of St. John's wort. First, said Mueller, the new high-dose preparations were a big improvement over the traditional teas and oils. Beyond that, Licht Wer waged an aggressive campaign to establish the herb's scientific credibility by commissioning rigorous studies at independent universities and laboratories.
An overview of 28 clinical trials of St. John's wort, conducted by researchers at Ludwig-Maximilian University in Munich and published last year in The British Medical Journal, concluded that the herb had clearly outperformed dummy medication in relieving depression and showed very few side effects. Although several early studies indicated that the herb performed about as well as competing antidepressants, the reviewers refused to draw any conclusions because the studies had involved too few patients.
"Current evidence is inadequate to establish whether hypericum is as effective as other antidepressants," the researchers wrote in The British Medical Journal. "Additional trials should be conducted to compare hypericum with other antidepressants in well-defined groups of patients; to investigate long-term side effects; and to evaluate the relative efficacy of different preparations and dosages."
Since then, several other studies have been published in which the herb appeared to perform well against a class of conventional antidepressants known as tricyclics, including imipramine.
Mueller and his colleagues at the University of Frankfurt ran experiments, meanwhile, indicating that the herbal extract had a chemical effect that was similar to that of conventional antidepressants, including Prozac. Writing in the German journal Pharmocopsychiatry, the researchers showed that the extract appeared to reduce the rate at which brain cells reabsorb an important neurotransmitting chemical called serotonin. That is the major mechanism behind Prozac and similar antidepressants. A low level of serotonin in the brain has long been associated with depression, and drugs like Prozac allow more serotonin to flow between cells.
But the experiments, carried out in test tubes as well as on rats, also showed that the herbal extract reduced the reabsorption of two other chemicals that are also associated with mood regulation: dopamine and norepinephrine. "I don't know of any other antidepressant that inhibits all three systems," Mueller said in an interview.
The researchers also noted that the herbal extract had a more modest tendency to bind with serotonin than Prozac. Other researchers now theorize that these differences may explain why the herb does not appear to touch off the side effects experienced by many patients using Prozac and its close relative Paxil: a loss of sexual drive, irritability, restlessness and weight gain.
Still, experts note that many of the patient studies have shortcomings. All but one of the studies involved patients with mild or moderate depression, and some included patients who barely qualified as truly depressed. Because none of the studies so far has been for more than six weeks, it remains unclear whether St. John's wort continues to be effective over the long term or whether unwanted side effects become apparent after long-term use.
Many German physicians and psychiatrists caution that the herb is not necessarily a cure-all. "A lot of people in Europe like the idea of something that is natural, but the effectiveness isn't always that strong," said Artur Wolf, a Frankfurt physician who recommends St. John's wort to some patients. "It is just one treatment on a broader pallette."
J.M. Cott, a clinical researcher at the National Institute of Mental Health in Rockville, Md., noted that these and another uncertainties "will continue to create skepticism" among mainstream American researchers.
Another important drawback is that all of the studies so far have tested St. John's wort against the older class of tricyclic antidepressants, rather than the newer Prozac family of drugs. The older tricyclic drugs are effective at reducing depression, but they have a much more scattershot effect on body chemistry and produce a wider range of side effects, including dry mouth, dizziness, fatigue, gastric distress and sweating. For practical purposes, experts say, the most relevant tests would be to pit St. John's wort against Prozac or its cousins.
In sharp contrast to the United States, though, Germany accepts many traditional herbal remedies as medicines. As a result, German manufacturers are allowed to describe on their packaging the herb's use in fighting depression and anxiety. And German health insurers are required to pay for the herb, just as they pay for conventional drugs.
"In Germany, we never lost our connection to herbal medicines," Mueller noted. Still, he said he remained skeptical that the seeming success of St. John's wort would be repeated with many other herbal remedies. "This is just by chance that we have a mixture that seems to turn out to be good," he said. "It does not mean that herbal medicines are better."