St. John's Wort for Depression

Despite lingering questions about its long-term efficacy and side effects, St. John's wort (Hypericum perforatum) is a popular over-the-counter herbal treatment for depression. An estimated 17% of Americans have used products containing St. John's wort. It ranks second, behind ginkgo, among top-selling herbal preparations in the United States.

Much of St. John's wort's recent popularity in the U.S. can be traced to a 1996 review of 23 clinical trials published in the British Medical Journal (BMJ). The review's authors concluded the herbal treatment worked better than placebo -- and sometimes as well as synthetic drugs -- for mild to moderate depression, with few side effects. But questions remained about dosing and preparation differences, its efficacy compared to conventional antidepressants, and long-term safety.

Since the BMJ article, more has become known about St. John's wort, and new questions have come up about its safety. The U.S. Food and Drug Administration considers it a dietary supplement, which exempts it from the testing and approval required of prescription drugs. But St. John's wort has drug-like uses and actions. Anyone wanting to try it should have information about its safety and efficacy. This is particularly so for women, who take St. John's wort more often than men do and seek treatment for depression twice as often.
St. John's wort update

* Until recently, hypericin, a reddish pigment found in St. John's wort's flowers, was thought to be responsible for its antidepressant activity. But scientists now think that other plant constituents --particularly hyperforin -- are involved.
* St. John's wort's mechanism of action remains unclear. Early studies suggested it was a monoamine oxidase (MAO) inhibitor, but recent research indicates a closer resemblance to selective serotonin reuptake inhibitors (SSRIs), minus the decrease in sexual drive experienced by 30- 40% of people taking SSRIs. St. John's wort should not be taken with MAO inhibitors or with SSRIs because the combination could result in serotonin syndrome, a disorienting, potentially fatal condition.
* St. John's wort appears to increase liver enzyme activity, which may inactivate certain drugs. It can reduce circulating levels of the immunosuppressant cyclosporine which, in several transplant patients, has resulted in organ rejection. It can reduce blood levels of the protease inhibitor indinavir (Crixivan), the blood thinner warfarin (Coumadin, and others), and the heart medication digoxin (Lanoxin). It also may intensify the effects of anesthesia, possibly resulting in over-sedation.
* Many studies have found that St. John's wort is as effective as older antidepressants such as imipramine for short-term treatment of mild to moderate depression. But how does it stack up against the newer SSRIs, especially for longer than two or three months? And how effective is it for severe depression? These unanswered questions are the focus of a major three-year multicenter study now underway sponsored by the National Institutes of Health. The study will compare St. John's wort, the SSRI sertraline (Zoloft), and placebo, in moderately to severely depressed patients.

Until We Know More

* If you're thinking about taking St. John's wort, discuss it with your physician, especially if you're on other medications or are scheduled for surgery.
* Most studies of St. John's wort used formulations manufactured in Germany of extracts standardized to a certain amount of hypericin (usually 0.3%) at a level of 500-900mg/day divided into three doses.
* To learn more:

The Alternative Medicine Foundation, Inc., (301) 581-0116:

The American Botanical Council, (512) 926-4900:

The National Center for Complementary and Alternative Medicine (NCCAM), Public Information Clearinghouse: nccam/fcp/factsheets

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