St. John's Wort Fails Another Test
Placebo works better than remedy for depression, study says
TUESDAY, April 9, 2002 (HealthDayNews) -- St. John's wort has a strong allure as an over-the-counter remedy that promises to ease depression, which is why sales of the herb top more than $400 million a year in the United States.
However, the deeds of this saint have failed to live up to its publicity. A new study has found that St. John's wort doesn't lift mood in people with moderately severe depression, but does cause several unpleasant side effects.
The findings, appearing in tomorrow's issue of the Journal of the American Medical Association, are the latest to undercut claims that the supplement is an effective therapy for the blues. About a year ago, scientists published similar results in the same journal.
Also, drug safety officials have warned that combining the compound with certain prescription medications, including treatments for AIDS and cancer, may have potentially dire consequences. Yesterday, Dutch researchers reported that St. John's wort may dilute the efficacy of the tumor drug irinotecan when the two are taken together. The scientists, who presented their results at a cancer meeting in San Francisco, say the findings may apply to other tumor treatments.
The latest study, led by researchers at Duke University, compared St. John's wort to the prescription antidepressant sertraline (sold as Zoloft) and to sham treatment in 340 men and women with moderately severe depression. The patients were seen at 12 clinics nationwide.
Those who received St. John's wort -- also known as extract of Hypericum perforatum -- were given between 900 milligrams and 1,500 milligrams a day of the LI-160 version of the supplement, a relatively familiar form produced by a German company.
People who took St. John's wort were less likely than those who received placebos to report significant elevations in mood after eight weeks, the researchers found. Nearly 32 percent of those in the placebo group showed much or very much improvement in symptoms, compared with about 24 percent of those who received the supplement, and 25 percent of those on Zoloft.
"What we saw was no benefit and side effects" from St. Johns' wort, says lead author Dr. Robert Califf, a cardiologist who directs the Duke Clinical Research Institute. These included frequent urge to urinate, swelling and failure to achieve orgasm during sex.
Zoloft didn't appear better than dummy treatment either, at least on the two main outcome measures (response at eight weeks and the number of people who reported major improvement). However, Califf says that's because the study was relatively small, and because some patients likely received inadequate doses of the drug.
"Every single one of the trends went in favor of [the medication]," he says. St. John's wort, on the other hand, showed no benefit on any measure of depression.
"If you're out there and feel depressed and take St. John's wort and feel better, it doesn't necessarily mean that the St. John's wort made you feel better," Califf says. "People with depression go up and down," often without regard to their therapy.
Indeed, the so-called "placebo effect" is quite strong in trials of depression treatments. A new report, also appearing in the journal, found that over the last 20 years, an average of almost 30 percent of subjects in the placebo arm of antidepressant studies improved during the trials.
The size of that effect has been growing over time, too, by 7 percent per decade, the researchers say. The share of patients who respond to active medication has also been rising over time, though not quite as steeply.
Dr. B. Timothy Walsh, a Columbia University psychiatrist and lead author of that study, says the increasing placebo effect may reflect a change in the subjects enrolling in depression trials.
"My hunch is that the character of people coming into these trials has changed. They have a less persistent form of depression than the people who entered the trials 20 years ago," Walsh says.
Depression is now much more widely appreciated; its symptoms are clearer and there's less stigma associated with the illness. It's also seen as quite treatable. It therefore seems plausible that study populations have milder forms of depression than they once did -- meaning they're more likely to improve on both active and placebo pills, he explains.
Dr. Uriel Halbreich, a psychiatrist at the University at Buffalo-State University of New York who has studied St. John's wort, says the latest findings might surprise some scientists who expected the supplement to be effective against depression. It still might be, Halbreich says, at least in those with mild cases of low mood.
Halbreich cautions there are roughly a dozen formulations of St. John's wort available to consumers. Some may work better than others, and some may work better for some people than for others. "It's very difficult to have a definite statement here," he says.
A study released last month found wide discrepancies in how eight brands of the remedy were formulated.
The Council for Responsible Nutrition, a trade group representing the supplement industry, branded the study as "misdirected and inconsequential." The group said the research was "targeted at moderate to severe depression, a use not recommended or supported for St. John's wort," the group said in a statment.
"It would be a shame if we discarded St. John's wort as a treatment for mildly to moderately depressed persons on the basis of these findings," Norman E. Rosenthal, a clinical professor of psychiatry at Georgetown University, says in the statement.
What To Do: To learn more about St. John's wort, check out the National Institute of Mental Health. For more on depression, try the National Depressive and Manic-Depressive Association.