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First Published Thursday, 9th October, 2008.

The herbal medicine St. John’s wort appears to work just as well as some prescribed antidepressants for treating patients with major depression, a new review finds. However, patients in German-speaking countries might experience the most benefit.

While there is public interest in the United States about whether St. John’s wort adequately treats depression, in some countries, like Germany, doctors commonly prescribe it for mild symptoms. Authors of the review found that studies with German patients did, in fact, have the best results.

“The most striking finding from our review is that trials from German-speaking countries have clearly more positive effects, both compared to placebo and standard antidepressants, than trials from elsewhere,” said lead reviewer Klaus Linde of the Centre for Complementary Medicine Research at Technical University in Munich. “In principle, we can say that hypericum extracts work in German-speaking countries, but we are less certain for other countries.“

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

A person could be experiencing major depression when depression symptoms interfere with his or her ability to work, sleep, eat and take pleasure in activities previously enjoyed. The symptoms usually last for at least two weeks, but can often last longer than several months. St. John’s wort, an extract of the plant Hypericum perforatum, is an herbal alternative for patients who do not want prescribed antidepressants.

Exactly how the herb works to treat depression is unclear, partly because the extracts can contain at least seven groups of components, according to the reviewers. There is also no regulation on what the extract must contain.

“There is no patent protection on herbs; therefore, more or less anyone can market hypericum extracts,” Linde said. “The products on the market vary enormously in their quality and content in active ingredients.“

Linde added that consumers should be aware that many St. John’s wort products on the market have very low concentrations (such as dosages of less than 300 milligrams per day), and therefore, probably act only by placebo effects.

The meta-analysis provides the best evidence to date of the effects of St. John’s wort in people with mild to moderate major depression and moderate to severe major depression.

The researchers say that although the review was limited to major depression and did not look at atypical depression, major depression is not necessarily the only or best indication for its use. They acknowledge that people with atypical depression may be particularly suited to treatment with St. John’s wort.

In the United States, the National Center for Complementary and Alternative Medicine (NCCAM), a division of the National Institutes of Health, reports that St. John’s wort is “of minimal benefit in treating major depression.” A study co-funded by NCCAM, found St. John’s wort to be no more effective than placebo in treating major depression of moderate severity.

Linde and his colleagues wrote a previous Cochrane review in 2005 on St John’s wort and concluded that it did reduce symptoms of mild to moderate depression. The significant difference between the 2005 review and the current one is the reviewers now include only studies restricted to major depression, while the older review included all depressive disorders.

“Compared to 2005, the evidence that hypericum extracts are effective is better now,” said Linde. “The new version also for the first time shows significantly fewer side effects associated with hypericum extracts compared to selective serotonin reuptake inhibitors.“

The current review evaluated 29 studies from a variety of countries – with a total of 5,489 patients – and all trials were randomized and double blind. The reviewers compared treatment of patients with major depression with extracts of St. John’s wort for four to 12 weeks with either placebo or tri- or tetracyclic antidepressants and selective serotonin reuptake inhibitors.

According to the reviewers, the St. John’s wort products tested in the trials were high- quality products and the daily extract dosages were between 500 and 1,200 milligrams.

The Cochrane reviewers concluded the available evidence suggests that hypericum extracts are superior to placebo in treating patients with major depressions and are “similarly effective” as standard antidepressants.

However Linde cautions that “using a St. Johns wort extract might be justified, but products on the market vary considerably, so these results only apply to the preparations tested.“

The researchers advise that those wishing to take St. John’s wort should consult a health professional about the best preparation for them, and the risks and benefits compared to standard antidepressants.

John Williams, MD, director of the Duke Evidence-based Practice Center at Duke University and Durham VA Medical Center, has also done research on the use of St. John’s wort for depression and disagreed that patients with major depression should turn to the product.

“Given the inconsistent evidence about efficacy in major depression and the questionable quality of over-the-counter products, St. John’s wort should not be a first or second choice for U.S. patients with moderate to severe major depression,” he said.

Williams added, however, that for patients with minor depression, where the evidence for St. John’s wort “is more robust,” it might be an option for patients who can find quality products.

The review disclosed that each author has received speaking or travel reimbursement fees from German drug manufacturer Schwabe.

Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database of Systematic Reviews 2008, Issue 4:CD000448   [Abstract | Full text ()]