Archive

Reactions to Recent St. John's Wort Study

Dr. Cass is interviewed on the CBS Evening News with Dan Rather on April 17th. CBS News Correspondent Byron Pitts reports on a newly published study of St. John's wort by Vanderbilt University:

Psychiatrist Dr. Hyla Cass recommends St. John's wort for many of her patients. "I know the research, I know that it does work, but every time it works it's like a miracle to me, to think that this little yellow flower has such potency."

The following is Dr. Cass' analysis of the Vanderbilt study as published in the Journal of the American Medical Association.

LATEST ST. JOHN'S WORT STUDY IN JAMA DOUBTS ITS EFFECTIVENESS, BUT THE BOTTOM LINE IS:

For those of you taking or considering taking SJW for mild to moderate depression, you have nothing to worry about. This study does not negate the many fine studies that have shown SJW to be just as good as the antidepressants in treating mild to moderate depression, or "the blues".

Summary of my objections to the article's conclusions:

1. The majority of studies on SJW and depression were for mild to moderate, not severe depression.
    
2. The group was too small for any valid conclusion (200 subjects). It might be seen as a preliminary study. Meanwhile, Shelton discounts the validity of the over 25 published studies, on over 1700 patients.
    
3. The author fails to discuss Dr. Vorbach's successful study with SJW and severe depression.
    
4. The study design is in question because of the very low placebo response: 4.9% versus an expected 20-50% in other studies (and the SJW group still did 3 times as well!). This may be because no "active" drug was given, which may have prejudiced examiners. They would expect no effects from a dummy pill, especially since there was no chance of either pill being an "active, successful antidepressant." (Beware, ye of little faith!)

A new clinical study on the popular herb St. John's wort published in the Journal of the American Medical Association (JAMA) concludes that St. John's wort (SJW) is not effective in treating major or severe cases of depression. The study was conducted by Dr. Richard C. Shelton of Vanderbilt University and sponsored by Pfizer, the pharmaceutical manufacturer of sertraline (Zoloft ®), a leading anti-depressant drug.

Description: The study was placebo-controlled, double-blind, with 200 subjects over 8 weeks, with half receiving SJW and half a placebo (or dummy pill). During the course of the study, neither the individual nor the researcher knew who was getting which product. The dose was 900 mg. daily for 4 weeks, increasing to 1200 mg if there was no response, up to 8 weeks total.
[Shelton et al. JAMA 2001; 285:1978-1986]

The article questions, with little basis, the validity of the over 25 studies done to date on the use of SJW in mild to moderate depression. While these "questionable" studies were done in Europe, mostly in Germany, they were published in peer-reviewed journals, including the British Medical Journal (BMJ). I will summarize a 1996 review article below for comparison purposes.

Linde's BMJ meta-analysis reviewed 23 controlled studies involving 1,757 depressed patients, [the JAMA/Pfizer study had only 98 patients] and found that St. John's wort is three times more effective than a placebo, and as effective as prescription antidepressants, but without the side effects. (This is the same percentage as the JAMA study, though they considered this result insignificant.) Fifteen studies compared the herb with a placebo, and eight compared it with conventional antidepressants.

Details: The four-to-eight week placebo-controlled studies found St. John's wort to be significantly superior. The daily dosage levels ranged from 350 mg to 1,000 mg of standardized 0.3% hypericum extract (0.4 mg to 2.7 mg per day of hypericin). An average of 55.1% of the hypericum users responded to the treatment, much higher than the 22.3% response rate of the placebo group. Most of the trials were carried out with the compound, LI160 (Jarsin300), available in many pharmacies under the brand name Kira.
[Linde K, et al, St. John's wort for depression — an overview and meta-analysis of randomized clinical trials British Medical Journal 313(7052), 253-258, 1996.]

There is, in fact, one published study using SJW in severe depression. Dr. Ernst-Ulrich Vorbach and colleagues in Germany conducted a multi-center study with 209 severely depressed patients, of whom 38 were hospitalized at the time. [Pharmacopsychiatry, 1997,30(suppl):81-85]. They were given 1800 mgs daily, versus Shelton's 900 mg for 4 weeks, increasing to 1200 mg if no response, and compared it to imipramine, a tricyclic antidepressant. While the results in the two groups were similar, the side effects in the SJW group, despite the high dose, were far lower. So, SJW may, after all, be useful for severe depression, given in the right dose, and with a researcher who is familiar with its clinical use. Can you imagine a Pfizer study that gives the patients a half dose of Zoloft, then concludes that their product was ineffective?

Other experts' comments about the study protocol:

In an American Botanical Council news release, Jerry Cott, Ph.D., former Chief of Psychopharmacology Research Program, at the National Institutes of Mental Health, makes this point: "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. 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. 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, an acknowledged expert on the effects of herbs as well as conventional drugs on mental disorders, including depression, 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."

Dr. Cott added that this study would be considered a "neutral" study, since no active treatment group, 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. Moreover, "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."

So, the fact that the JAMA study had a placebo response rate of only 4.9% is an oddity, to say the least. Despite this low number, the SJW remission rate was nearly three times better than placebo, at 14.3%!

According to Mark Blumenthal, founder and executive director of the nonprofit American Botanical Council (www.herbalgram.org), most of the previous clinical studies conducted in Europe on SJW targeted only mild to moderate cases of depression, not major or severe depression, and he points out that "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 adds, "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." (HC's note: Don't forget about Dr. Vorbach's successful study with severe depression and SJW.)

Conclusion: In my own practice, and in the many e-mails I have received from now-happy users of SJW, I would agree. It may not be the 'magic bullet' but it certainly has a significant role in the treatment of depression. For more information on St. John's wort, check out my book St. John's Wort: Nature's Blues Buster, as well as St. John's wort frequently asked questions (SJW FAQ) on this site.

Notes:

1. 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. Information for consumers and healthcare professionals about herbal medicine may be found on the organization's website www.herbalgram.org.

2. Another website for herbal information is the American Herbal Products Association (AHPA.org), the national trade association of the herbal products industry. Together with its members, leaders in the industry, the organization has been setting standards of quality for its members, who use Good Manufacturing Practices (GMP's) to ensure the highest quality in herbal products.

Michael McGuffin, the President of the AHPA, sent a letter to the editor of the New York Times in response to the JAMA St. John's wort study. It was published in the April 25th edition of the paper.

The content provided by this site is for informational purposes only and has
not been approved by the U.S. FDA. This site is not intended to provide
personal medical advice, which should be obtained from a medical professional.

©2008 cassmd.com, all rights reserved.