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Sept. 1, 2000 -- So, many of you may have heard that St. John's wort works for milder depression, right? But, does it really? Study results to date have been conflicting. But a recent German study says it really does the trick, when compared with an older antidepressant. So, is that the final answer? Nope: U.S. experts remain cautious about research findings and warn that there are lots of other problems associated with taking the herb.
"In this study we investigated more than 300 patients with mild to moderate depression -- this is very important: it did not include severe depression. We compared two groups: one group received a well-known synthetic antidepressant drug, imipramine [one of its trade names is Tofranil] and the other group received St John's wort extract," study author Helmut Woelk, tells WebMD. "We found that therapeutically there was almost no difference in effectiveness for treating mild to moderate depression, but the rate of side effects was much lower in the [St. John's wort] group." Woelk is the medical director of the Clinic for Psychiatry and Psychotherapy and a professor of psychiatry at the University of Giessen in Germany.
In the study, published in the Sept. 2 issue of the British Medical Journal, Woelk and colleagues randomly divided 324 patients with mild to moderate depression into two groups: one group got imipramine, which is among an older group of antidepressant drugs called tricyclic antidepressants, twice daily for six weeks, and the other got St. John's wort extract twice daily for six weeks.
Patients improved on both treatments, and to the same extent, but nearly two-thirds of the patients taking imipramine reported side effects, compared to just over a third of those taking St. John's wort. Side effects caused 16% of patients taking the antidepressant and 3% of patients taking St. John's wort to drop out. Some of the common side effects noted for the antidepressant are dry mouth, nausea, dizziness and sweating.
"The study is important because there are a lot of patients -- millions worldwide -- with mild to moderate depression," says Woelk, noting that the World Health Organization estimates 3% to 5% of the population suffer from it. "These patients could take [St. John's wort] instead of synthetic compounds with side effects -- and a lot of patients interrupt their treatment because of the side effects. So one can say [St. John's wort] could be a first-line treatment for this group of depressives."
In fact, Woelk expands the possibilities of the herb to the newer antidepressants by saying he's seen patients drop out from side effects from both the older and the newer versions of the synthetic drugs.
But St. John's wort still remains to be tested head-to-head against the new group of antidepressants, called selective serotonin reuptake inhibitors, such as Prozac, and other new compounds.
One expert says that Tofranil "is no longer prescribed very often for treating depression. It has been pretty much replaced by newer drugs like Prozac and Paxil," Gregory Gray, MD, PhD, tells WebMD. "One of the reasons that Prozac etc. became more popular is that they had fewer side effects than . A more important question would be how does St John's wort compare, in terms of side effects, to drugs that we more commonly use." Nonetheless, Gray, a professor and chairman of the department of psychiatry at Charles Drew University in Los Angeles and vice chairman of the psychiatry department at UCLA, calls it an "interesting study" with newsworthy findings.
U.S. experts have other concerns, too. In Germany, the use of St. John's wort to treat depression goes back about two decades: there are many studies that investigated its safety and usefulness, and the quality of the extract is closely monitored. Additionally, at higher doses, it must be prescribed by a doctor. But in the U.S., it is still a fairly untested and unregulated herb -- and that makes many in the medical establishment very cautious about jumping on the bandwagon.
"In the US, [an] issue is that preparations are not standard, so you are not sure what you are actually taking when you buy over-the-counter," says Ranga Krishnan, MBBS, chair of the department of psychiatry at Duke University in Durham, N.C.
Gray agrees. "The study used a particular preparation that is sold in Germany. But if you were to go to the drug store in the U.S., you wouldn't find that same preparation. And if you looked for something that supposedly has the same amount of St John's wort extract in it, there have been reports that many of these preparations are quite variable in terms of the composition: they either had very little or more than what appears on the label," says Gray. "My personal opinion is St. John's wort probably is an effective antidepressant. On other hand, until the preparations have more consistency, it would be hard to recommend that somebody go out and take it."
A spokesperson for National Institute of Mental Health says the government agency has reviewed the literature on St. John's wort and determined there was sufficient evidence to fund a large, multicenter study on it, which is currently being organized at Duke University by Krishnan and his colleagues; results aren't expected until the end of the year. Another study, funded by Pfizer and organized by Vanderbilt Medical Center, found no difference in effectiveness between St. John's wort and a placebo.
"I think the [German findings] are interesting, showing the two drugs are equally effective, but there are some problems with the study," Krishnan tells WebMD. "The main one is there is no placebo group, and without a placebo group you can't tell if either drug beats placebo. It could mean both drugs worked or both drugs didn't work. And that is a problem interpreting the study.
"My guess its that it is effective, but on the other hand I also know that my guesses may be wrong," says Krishnan, adding that until the results from the Duke trial are in "it will be very hard to know for certain." In the Duke trial, St John's wort is compared to both another common antidepressant (Zoloft) and a placebo.
Another major concern is possible interactions between St John's wort and other drugs. In February of this year, the FDA warned physicians that St. John's wort dangerously interferes with a long list of prescription drugs, including the AIDS drug Crixivan (indinavir) and the immunosuppressive drug Neoral or Sandimmune (cyclosporine), which is used by patients who have received transplants. In May, leading makers of St. John's wort adopted a voluntary labeling program urging all users of the dietary supplement to seek the advice of their "health professional" prior to using it. Still, some experts wonder if more regulation is needed.
"Although it is an herb, one has to remember it is still a drug and has the same issues that any other drugs has," says Krishnan.