St. John's Wort Only Minimally Effective In Relieving Major Depression, Review Confirms

The updated review of 37 trials, involving 4,925 patients, reaffirms earlier findings that St. John’s Wort:

--Reduces symptoms of mild-to-moderate depression among adults in a manner similar to antidepressant drugs;

--Causes fewer side effects than some of the older antidepressants on the market; and

--Causes slightly fewer side effects compared with selective serotonin reuptake inhibitors, or SSRIs, the class of antidepressants most recently developed.

The review was led by Professor Klaus Linde of the Centre for Complementary Medicine Research at Technical University in Munich, Germany. The reviewers caution that “uncontrolled use of [St. John’s Wort] is problematic because serious interactions can occur” with a number of frequently used antidepressants and that physicians should regularly ask their patients about their use of St. John’s Wort.

The National Center for Complementary and Alternative Medicine, part of the National Institutes of Health, holds that St. John’s Wort is not a proven therapy for depression.

The review appears in the most recent issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

All studies were double-blind, randomized clinical trials involving patients with depressive disorders. All involved comparisons between St. John’s Wort and placebos or synthetic antidepressants given for at least four weeks.

St. John’s Wort is available over the counter in the United States, where lifetime depression has an estimated prevalence of 16 percent.

In Europe, St. John’s Wort generally can be obtained only by prescription and is used to treat anxiety and sleep disorders as well as depression. St. John’s Wort has been subject to more trials in Europe, especially in German-speaking countries, than in the United States. However, because it is prescribed for a number of disorders other than depression, Linde and colleagues included in their review only those trials from German-speaking countries that were restricted to patients with a diagnosis of major depression.

St. John’s Wort, scientifically referred to as hypericum extracts, derives its name from the patron saint of nurses and Old English word for “plant.” The mechanism by which it acts is unclear, but St. John’s Wort is known to contain at least seven groups of components that may contribute to its pharmacological effects. While some of the components individually have been shown to have a positive effect on some forms of depression, the total extract seems more clearly beneficial.

Hypericum extracts are decidedly less expensive than some of the most widely prescribed antidepressants, such as Prozac. However, the composition of St. John’s Wort depends on the raw plant material used, the extraction process and the solvents used. As a consequence, the review notes, “the amounts of bioactive constituents in different products can vary enormously.”

Reviewers recommend that St. John’s Wort products should be avoided if they do not provide important content information, such as the amount of total extract contained, the extraction fluid used and the ratio of raw material to extract. They also call for more detailed studies of the constituent components of St. John’s Wort.

Dr. John Williams, a professor of medicine and psychiatry at Duke University who has studied St. John’s Wort in the context of depressed patients in primary care facilities, says the Linde review has made him more cautious in his outlook on the product. Williams says he currently feels St. John’s Wort should not be “a first or second choice for U.S. patients with moderate to severe major depression.” At the same time, he says, the product remains a “reasonable option” for patients suffering from minor depression — as long as they are able to locate “quality preparations.”

In their review, Linde and colleague Michael Berner acknowledge potential conflicts of interest: Linde, for once receiving travel expense reimbursements from Schwabe, a manufacturer of St. John’s Wort; and Berner, for a past research grant and travel expense reimbursement for speaking at a meeting organized by Schwabe.

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Linde K, et al. St John’s Wort for depression (Review). The Cochrane Database of Systematic Reviews 2005, Issue 2

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.