Questions Raised About Latest St. John’s Wort Study in JAMA

Austin, TX (April 13, 2001) A new clinical study on the popular herb St. John’s wort is being published this week in the Journal of the American Medical Association, according to a press release from JAMA (embargoed for Tuesday, April 17). The study reportedly shows that St. John’s Wort (SJW) is not effective in treating major or severe cases of depression.

According to Jerry Cott, Ph.D., former Chief of Psychopharmacology Research Program, at the National Institutes of Mental Health, this does not necessarily invalidate the use of SJW in major or severe depression. In Dr. Cott’s estimation, this study would be considered a “neutral” study. No active treatment arm, i.e., no active pharmaceutical drug, was used in the design of the study to compare the SJW and the placebo (dummy pill) to the activity of the drug. Dr. Cott is an acknowledged expert on the effects of herbs and conventional drugs on mental disorders, including depression.

“What strikes me initially is the very low placebo response rate in this study. In my 25 years of psychopharmacology research, I have never seen a depression study with such a low placebo response,” he noted. “One possible interpretation is that the extremely low placebo response rate should invalidate the study. Others might say the low response rate is due to the high quality of the investigators. And this is certainly true. They are all fine and experienced investigators,” he added.

“However, these are the same investigators that routinely see placebo response rates of 30 to 50 % in their other drug company studies. So, why the difference now?” he asks.

Dr. Cott suggested the following explanation: “I would venture to guess that the rate was low because of the possibly subconscious expectations of the investigators, the raters and the patients. Their expectations may have been low because there is no ‘active’ drug in this study; they may not have expected much from the St. John’s wort in the first place. That is, in the minds of some, this was a clinical trial comparing two inactive treatments. Therefore, the expectation of all concerned is that no one would get better. And this was nearly the case, though one has to read very carefully to see that St. John’s wort did perform better than placebo.”

He added, “Perhaps a better-designed study would have incorporated an ‘active’ comparison, to raise the possibility in the minds of the researchers that a particular patient may be among the 30% on the ‘active’ medication.”

According to Mark Blumenthal, founder and executive director of the nonprofit American Botanical Council, most of the previous clinical studies conducted in Europe on SJW targeted only mild to moderate cases of depression, not major or severe depression. “There is a significant body of research and clinical experience that documents the safety and efficacy of St. John’s wort to treat mild to moderate cases of depression,” he noted.

He added, “Although federal law does not allow marketers of St. John’s wort to make claims for treating depression or anxiety disorders, most of the products I have seen in the United States appear to be targeting consumers who want to gently elevate their moods, not treat a severe case of depression.”

The study was conducted by Dr. Richard C. Shelton of Vanderbilt University under a grant from Pfizer, the pharmaceutical manufacturer of sertraline (Zoloft ), a leading antidepressant drug. The Shelton study will appear in this week’s issue of JAMA.

Founded in 1988 in Austin, Texas, the American Botanical Council is the leading independent non-profit research and education organization that educates the public on the responsible and scientific use of medicinal plants. Its quarterly journal HerbalGram has been published since 1983 as a reliable and authoritative source of herb and medicinal plant research, regulatory and market issues, native plant conservation and other general interest aspects of herb use. Information for consumers and healthcare professionals about herbal medicine may be found on the organization’s website www.herbalgram.org.

Study references: (Shelton et al. JAMA 2001; 285:1978-1986)

Contact: Gayle Engels, phone (512)926-4900, fax (512)926-2345,

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