St. John’s Wort Still Effective for Mild, Moderate Depression

The effectiveness of St. John’s wort (Hypericum perforatum) is comparable to prescription antidepressants for the treatment of mild to moderate depression, according to a report in Phytomedicine (2002;9:468–4) that reviewed previously published clinical trials.

In this review, the authors compiled the results of 34 double-blind clinical trials that included a total of 3,000 people with depression. In placebo-controlled trials, St. John’s wort consistently outperformed the placebo in its antidepressant effect. When St. John’s wort was compared with conventional antidepressant medications like imipramine (Impril®) or fluoxetine (Prozac®), it was found to be either as effective as, or superior to, drug treatment.

The most effective intake level of St. John’s wort was found to be between 500 and 1,000 mg of standardized alcohol extract per day. The most commonly recommended amount of St. John’s wort is 300 mg of standardized extract, three times daily. The effect of St. John’s wort did not appear to vary greatly with differently prepared extracts. There are several different standardized extracts of the herb commercially available.

The incidence of side effects was significantly lower with St. John’s wort than with pharmaceutical antidepressants. Only 1 to 3% of people taking St. John’s wort reported adverse effects, compared with 20 to 50% for the conventional medications.

While the incidence of side effects with St. John’s wort was very low, there is a risk of adverse interactions with other medications. St. John’s wort has been shown to reduce the therapeutic action of many drugs, including warfarin, cyclosporine, and birth control pills. People wishing to take St. John’s wort should first check with their doctor if they are taking any medications.

Depression is a common condition, with an estimated one in four people reporting symptoms at some time in their lives. Women are twice as likely to suffer from depression than men.

The mechanism of action of St. John’s wort is still under debate. Some research indicates that its benefits, like those of most other antidepressants, are the result of changes in the levels of certain chemical messengers (neurotransmitters). Other studies indicate that the therapeutic effect comes from changes in the production of immune system chemicals known as cytokines.

There has been some debate in the research literature in the past two years about the efficacy of St. John’s wort. Two studies published in the Journal of the American Medical Association (JAMA) concluded that St. John’s wort was ineffective for the treatment of depression.

The first clinical trial, published in 2001, found that nearly three times as many people taking St. John’s wort had complete recovery compared with those taking placebo. However, because the overall number of people who had symptomatic relief after taking St. John’s wort was low (14%), the authors concluded that it should not be recommended for people suffering from depression. Most effective pharmaceutical treatments for depression have a 50% or greater response rate in clinical trials. Also notable about this study was the fact that only 5% of the people taking placebo had symptomatic improvement, a number much lower than the 30% usually seen in this type of study. The low placebo response rate suggests that the participants selected for this trial were "poor responders" (i.e., unlikely to respond to any treatment).

In the second of the trials, published earlier this year, people taking St. John’s wort actually had slightly less benefit than those taking the placebo. Also in this trial, the drug sertraline (Zoloft®) did not result in significant benefit compared to the placebo. As both St. John’s wort and sertraline have been found to be superior to placebo for the treatment of depression in many other trials, there appear to have been significant differences in the design of this study compared to previously published reports.

It is not surprising that there is considerable variability in the results of clinical trials assessing St. John’s wort for depression. Psychological symptoms are notoriously difficult to rate objectively in clinical research, resulting in an over or underestimation of clinical response. Also, many people suffer from treatment-resistant depression, and will thus be unlikely to respond to either active treatment or placebo in clinical research.

Because of the inherent difficulty in designing clinical trials that evaluate treatments for depression, clinical reviews like the one published in Phytomedicine are useful for helping to see the big picture. Despite the negative reports from JAMA, the bulk of the evidence to date strongly indicates that St. John’s wort extract is a viable treatment option for people with mild to moderate depression. The favorable side effect profile, along with the relatively low cost of the herb, makes it a sensible first line treatment for many people with depression.

Matt Brignall, ND is a graduate of the University of Michigan and Bastyr University. He works at the Seattle Cancer Treatment and Wellness Center, where he specializes in complementary medicine approaches to cancer. He has been published in several journals, including Alternative Medicine Review, Coping With Cancer, and the Journal of the National Cancer Institute. Dr. Brignall also teaches clinical nutrition at Bastyr University in Kenmore, WA. He is a regular contributor to Healthnotes, Healthnotes Newswire, and the Healthnotes Quick!Reference series.

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