Industry Refutes JAMA Study Regarding St. John's Wort and Depression

Industry Refutes JAMA Study Regarding St. John's Wort and Depression

DURHAM, N.C.--Neither St. John's wort norsertraline, a pharmaceutical, are effective against severe depression, according to a major clinical trial funded by the National Institutes of Health(NIH) and published in the April 10 issue of the Journal of the American Medical Association (JAMA) (www.jama.com).Sertraline, or Zoloft® by its brand name (manufactured by Pfizer Inc.), is the third best-selling selective serotonin reuptake inhibitor--sales reached $2.14 billion in 2000--and the leading antidepressant in terms of share of new prescriptions, according to Med Ad News. St. John's wort(Hypericum performatum) is a first-line treatment for depression in Germany, with an estimated 131 million doses prescribed by German psychiatrists in 1999. And, according to Nutrition Business Journal, sales of St. John's wort in 2000 were worth approximately $180 million.

The JAMA study, which was led by researchers from Duke University in cooperation with 11 other centers in the United States, was conducted from December 1998 to June 2000. Patients (n=340) were randomly assigned to one of three treatment groups for an eight-week period: St. John's wort extract (as Jarsin® 300 mg, manufactured by Germany-based Lichtwer Pharma and distributed by New York-based Abkit), sertraline (50 to 100 mg of Zoloft), or placebo. Those patients who responded to treatment continued the regimen for an additional 18 weeks. Interestingly, patients in the placebo group responded more favorably than either treatment group.

According to industry associations and other scientific organizations, this study does not invalidate the use of St. John's wort in clinical depression, nor does it invalidate the use of sertraline. "Both St. John's wort and Zoloft have been shown to be safe and effective in previously published clinical trials," said Mark Blumenthal, executive director of the American Botanical Council (ABC). "Zoloft is a known effective drug. It's just as easy, in the case of this study, to conclude that Zoloft does not work as it is to conclude St. John's wort doesn't work. ... That doesn't mean they don't work, it just means that they did not work in this particular study for a variety of reasons."

Industry members questioned the validity of these study results on several levels. The first argument is that clinical trials meant to determine the efficacy of any treatment against depression are highly likely to fail. "One-third of drugs tested for depression fail to show the drug is any more effective than placebo," said Steven Dentali, Ph.D., vice president of scientific and technical affairs for the American Herbal Products Association (AHPA). "And that's not because the drugs don't work, it's because of the difficulty of conducting a successful trial of that nature."

The second argument is that the results of depression trials are invariably difficult to measure, as opposed to, say, testing the efficacy of treatment for lowering cholesterol--which can be definitively measured. "The study simply lacked the sensitivity to detect a difference," said Jerry Cott, Ph.D., scientific advisor for AHPA.

Blumenthal agreed, adding, "[This study] wasn't sensitive enough to pick up a response. [The researchers] have done some secondary clinical endpoints, and they found that Zoloft worked a little better than St. John's wort. But, the fact of the matter is, the rules for interpreting a clinical study like this say that you have to evaluate the study based on the primary, not the secondary, results. So the primary results showed that both of them failed."

The third argument is that the study population consisted of severely depressed patients, when St. John's wort is only recommended for mild to moderate cases of depression. "This new report dismisses the scientific fact that St. John's wort has been proven safe and beneficial for the treatment of mild to moderate depression, stress and anxiety, according to a substantial body of evidence in the medical literature based on more than 30 controlled clinical studies and three meta-analyses or systematic reviews," said John Cardellina, Ph.D., vice president of botanical science and regulatory affairs for the Council for Responsible Nutrition (CRN).

Another problem with this particular study is the reason study authors gave for studying St. John's wort in this way. "The study says that people are taking [herbs] to avoid the adverse effects of drugs, that they may be self-medicating when they need effective drug treatment and psychotherapy," Dentali explained. "[St. John's wort] is a complement to the treatment of depression. It's not an alternative and never was intended to be. It's not used as one for severe or major depression. If people have major depression, they need to get drug therapy and counseling."

Also, the tone used by study authors in reporting their findings was objectionable to industry members. According to a CRN press release, "the JAMA authors downplay the fact that St. John's wort did no worse than a known, effective antidepressant in the two most important primary outcome measures of the study and, instead, emphasize only the botanical's lack of efficacy for an unintended use."