Questions and Answers about St. John's Wort
There is considerable public interest in claims that extracts from the herb Hypericum perforatum, commonly known as St. John's wort, may be an effective treatment for depression. Although St. John's wort is widely prescribed in Europe, no studies of its long-term use have been conducted, and published studies have treated different types of patients and have used several different doses. The National Institute of Mental Health (NIMH), in collaboration with the NIH Office of Alternative Medicine (OAM) and the NIH Office of Dietary Supplements (ODS), is beginning the first U.S. large-scale controlled clinical trial to assess whether Hypericum has a significant therapeutic effect in patients with clinical depression.
This three-year study, coordinated by Jonathan Davidson, M.D., at Duke University Medical Center, will include 336 patients with major depression, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Patients will be assigned randomly to one of three treatments for an eight-week trial. One-third of the participants will receive a uniform dose (900 mg daily) of St. Johnï¿½s wort, another third will receive placebo, and the other will take a selective serotonin reuptake inhibitor (SSRI), commonly prescribed for depression.
NIMH cannot recommend the use of St. John's wort at this time. What is known about St. John's wort at this point falls short of the kind of scientific information that will be available upon completion of this rigorous and well-designed clinical trial. There are already several widely available treatments for depression with proven efficacy and safety. NIMH welcomes any novel treatment for depression, a brain disorder that affects more than 17 million adult Americans each year. Research has shown that as many as 70 to 80 percent of patients respond positively to treatment with antidepressant prescription medications, short-term specific psychotherapies, or a combination of both. Those seeking treatment for depression should consult their doctor to determine which treatments are most likely to be useful.
1. What is St. John's wort?
St. John's wort, whose botanical name is Hypericum perforatum, is a plant with yellow flowers that commonly grows in the wild. In the United States, it is sold in pill and liquid forms in health food stores and pharmacies as a nutritional supplement. It is not regulated by the U.S. Food and Drug Administration and cannot be prescribed by doctors in the United States.
2. What do European studies using St. John's wort to treat depression show?
An overview of 23 clinical studies in Europe, published in the August 3, 1996, British Medical Journal, found that the herb may be useful in cases of mild to moderate depression. The studies, which included 1,757 outpatients, reported that Hypericum was superior to placebo and appeared to produce fewer side effects than standard antidepressants.
3. Why is NIH doing a study, if the European results were this promising?
The completed studies are important, but data are limited. The doses in the European studies were not standardized and the trial lengths not sufficiently long to yield definitive evidence that St. John's wort is superior to placebo. The inclusion criteria for patients also varied. NIMH concluded that studies should also assess the risk of relapse and the occurrence of side effects that may occur with long-term use.
4. Are there any dangers in taking St. John's wort?
"Natural" substances can have harmful side effects, especially if taken with other substances, or in large quantities. Since St. John's wort is not a proven therapy for depression, there is some risk in using it. Clinical depression is a serious medical disorder that can be debilitating and can lead to suicide. Currently the effective, proven treatments are antidepressants, short-term specific psychotherapies, or a combination of both. Since other medical conditions, such as thyroid disorders, can also mimic depression, anyone with symptoms of depression should receive a thorough medical examination to rule out other possible causes of the symptoms.
5. How can I enroll in the study?
The clinical trial is being coordinated at Duke University Medical Center in Durham, North Carolina, by Jonathan Davidson, M.D., and will include about 10 sites in various parts of the country. When the sites are identified by the end of 1997, individuals may contact Duke University Medical Center. Anyone who lives near a site or is willing to travel may apply.
6. Who will be excluded from participating in the study?
People who are severely depressed, especially those who may be suicidal, who require hospitalization, or who had taken St. John's wort before and had not tolerated it well will not be eligible.
7. How long will the study last?
The acute controlled phase of the study will last 8 weeks, to be followed by a 4-month follow-up of the patients who have responded to treatment. It will take about three years to complete enrollment and follow-up of 336 patients, and the data analysis is expected to be completed some months later.
8. Are there side effects involved in taking St. John's wort?
The European studies reported that some patients have complained of dry mouth, dizziness, gastrointestinal symptoms, increased sensitivity of sunlight, fatigue, and confusion. But these problems were usually mild.
9. What are the active ingredients in St. John's wort?
It is not known which components of the herb are active. The extract from St. John's wort contains polycyclic phenols, hypericin and pseudo hypericin, the presumed active components, in addition to flavinoids (hyperoside, quercitin, isoquercitrin, rutin), kaempferol, luteolin, biapigenin, and hyperforin.
10. Why is this study important?
The public has expressed growing interest in herbal products to treat mental and other illnesses and wants scientific evidence to support their use in treatment. A clinical trial of St. John's wort will benefit both patients and clinicians, because it will be based on a well-defined sample of adequate size and duration and will assess whether the herb is effective and safe.
Source: National Institute of Mental Health, National Institutes of Health