The Un-Drug

A first-line herbal remedy for the blues?

By Hara Estroff Marano, published on August 01, 2009

This is a story about an herb that is commonly used as a first-line remedy for the blues, hypericum perforatum, generally known as St. John's wort. "Popular Herbal Remedy Fails to Relieve Depression," headlines trumpeted in April 2001, based on a report in the Journal of the American Medical Association (JAMA).

But depression is a shadowy world in many ways. Somewhere before the blues turn black and self-perpetuating, the joy drains out of life. Is that a normal trough or a diagnostic category? It all depends on how (and when) people suspect that something is wrong.

The shadows inherent in a malady like depression lengthen dramatically when there are agents to be tested for treating it. On precisely which nerve ending does psychic pain dance and how do you target it? To get right down to it, how do you interpret a study which showed that, indeed, St. John's wort failed to produce a therapeutic response -- but which failed to drop the other shoe in public. Not only did St. John's wort not work, neither did the placebo pill it was pitted against, when placebos have a 30% to 50% response against depression on their own.

In response to numerous questions raised by the JAMA study, and concerns about the outcome of a major study of St. John's wort funded by the National Institutes of Health and due to be released later this summer, the Council for Responsible Nutrition recently convened a press conference to air important issues in the evaluation of drugs against depression. Among the points:

* Depression is a difficult disorder in which to test drugs. Fifty percent or more of trials of antidepressants fail to show a response.

* "No one single trial can ever be considered definitive," declared neuropsychopharmacologist Jerry Cott, Ph.D., former chief of psychopharmacology research at the National Institute of Mental Health. "You have to weigh all of the clinical trials."

* There are at least 31 trials of hypericum in the peer-reviewed literature showing it is beneficial for mild to moderate depression. "When one shows no benefit, you just don't discard 31 trials and change clinical practice," explained Tieraona Low Dog, M.D., assistant clinical professor of family medicine at the University of New Mexico.

* Patient selection is crucial. Patients selected for the JAMA study were chronic refractory depressives, observed Norman E. Rosenthal, M.D., clinical professor of psychiatry at Georgetown University. "On average they had depression for two years with many agents having been tried before. In my experience with depression at that level and with that history, any simple intervention is unlikely to work."

* A study must be designed with enough sensitivity to demonstrate effects. One important way of achieving this is to include a comparison antidepressant of known effect. However, no such comparison drug was used in the JAMA study.

* There is no one magic drug for all people. Depression is a complex disorder having many pathways through brain and body. Synthetic antidepressants do not work on all patients, nor are they acceptable to all.

* Many patients and physicians wish to have available a therapeutic agent that is not stigmatizing, has minimal side effects and that allows patients to make decisions for themselves about how to cheer themselves up.

What kills so many studies in depression is the high level of placebo response. One way to minimize the placebo effect is by increasing the severity of the illness. "Unfortunately," said Dr. Cott, "there's a very fine line between reducing the placebo response and reducing the response in the therapeutic category. There may have been a legitimate desire to improve the power of the study but it may not have had the desired effect."