New St. John's Wort Study Misleads Public

A recent study on the popular herbal remedy St. John's wort published in the April 10 edition of the Journal of the American Medical Association (JAMA) concluded that St. John's wort was ineffective in treating severe forms of depression. So was the widely prescribed antidepressant Zoloft® (sertraline)! The emphasis, though, both in the article and even more so, in the media's response, has been on the failure of St. John's wort in the treatment of depression, ignoring many published studies that have shown conclusively that St. John's wort is effective in the treatment of mild to moderate depression.

Why all the fanfare over the fact that St. John's wort is shown to be ineffective for a condition that it was never purported to treat? The bigger news is that this study showed that a drug with sales of over $2 billion and prescribed to millions of Americans for severe forms of depression may be no more effective than placebo. We are addressing a significant problem here: In the U.S, approximately 10% of people suffer from major depression at any one time, and 20-25% suffer a major depressive episode at some point during their lifetime.

Speaking as a clinician who regularly prescribes St. John's wort, I have seen repercussions from similarly slanted interpretations of an herbal study. While the placebo effect generally works in our favor, there can be a negative placebo effect, as follows. After hearing this news about St John's wort, many individuals who have been successful in relieving their depression with the herb may question their positive response, lose confidence in it, discontinue use, and revert to their depressive state. Many others may dismiss the St John's wort as useless without even giving it a try. Both groups may then turn to prescription medications, with their more severe side effects, such as loss of libido, memory impairment, headaches, nausea, and significant withdrawal problems. St John's wort's side effects, in contrast, are generally mild and transitory, with no withdrawal symptoms when it is discontinued.

St John's wort is known to have interactions with certain drugs, almost all of these for relatively small, specific populations (e.g. HIV patients on protease inhibitors, transplant patients on cyclosporin, those on coumadin, etc). Despite this, the overall risk/benefit ratio is far better than that of the prescription medications, and the drug/herb interactions are easily dealt with as with any active medication - with proper warnings and patient selection. I might add that grapefruit juice has a similar effect on drug potency, blocking liver enzymes that break down the drugs.

Depression can be a debilitating illness, and yet we are in effect "hexing" the use of a perfectly good herbal medicine that has been prescribed successfully in Europe for years as a first line treatment for mild to moderate depression. If it doesn't work, then the patient can always be given the more powerful, pharmaceutical antidepressants. Does St. John's wort lose its efficacy when it crosses the Atlantic? The medical profession is bound by the Hippocratic oath to "first do no harm," and to use the simplest, most natural, least harmful medicines first. Why put so many people as risk?

Perhaps the most interesting finding of this study is the power of the placebo effect, a belief in a substance's efficacy, reflected in the improvement of the group that received the dummy pills. In this study,, the placebo group actually responded better than both of the others (32% for placebo vs 24% for St John's wort and Zoloft) The human mind is complex, and many factors go into the healing process. Research shows the placebo effect to be a very significant aspect of treatment response for almost all medications. As physicians, we do best when we fully encourage and support it. Of course, there is no way to tell in any one individual how much relief is due to the placebo and how much, to the active medication, be it herb or drug. To JAMA's credit, an accompanying editorial actually addresses the issue, concluding that "this may be Nature's way of providing clues to fundamental aspects of the healing process, even as advances in medicine and the discovery of new therapies takes place. It is important to learn from rather than dismiss the variability of the therapeutic response." This might be the true news of this article.

We can make some generalizations about the media, herbs, and pharmaceuticals to be considered in evaluating this and other news stories:

The researchers' job is to get their research published.
The journal's job is to inform, but unfortunately, often with a pro-pharmaceutical bias. The pharmaceutical industry is by far the largest funding source of the journals (and of almost all of the research), as well as being one of the largest lobbying groups in Washington. Even though this study was NIH-funded, there is a complex web of relationships here. Most researchers also conduct other studies that are funded by this industry.
The media's job is to sell news, and generally, by being as sensational as possible. The public must read between the lines to ferret out the truth, and make up their own minds. We hope that this has been of some help in the process.

Re: Davidson JRT et al. Effect of Hypericum perforatum (St John's Wort) in major depressive disorder: A randomized controlled trial. JAMA. 2002;287:1807-1814.

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New St. John's Wort Study Misleads Public