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Eurotrends: St. John’s Wort—The International Debate

Recent study fuels herbal controversy.

St. John’s Wort—The International Debate



Recent study fuels herbal controversy.



By Joerg Gruenwald


St. John’s Wort is very well accepted as first line therapy for mild to moderate depression in Europe, especially in Germany and Switzerland where most of the clinical trials have been performed during the last 15 years. The market has grown to international proportions of approximately $250-300 million in retail sales, with the strongest market in Germany.

Recently a U.S. trial concluded that St. John’s Wort is not effective for the treatment of major depression, based on one clinical trial with 200 patients. It is well known in the industry and was indicated in the publication that Pfizer—manufacturer of prescription depression drug Zoloft®—not only funded the research but also was involved in the design and preparation of this study.

The PR Approach


Pfizer used the result of this study to create an immense PR campaign that St. John’s Wort is not effective for major depression. It did not mention the positive data from 23 clinical trials and the wide use in Europe. Strangely enough, Pfizer did not do any PR in Germany, the major market for St. John’s Wort. Approximately every third package of antidepressant prescribed in Germany is a St. John’s Wort product. For German physicians St. John’s Wort is usually the first line therapy for mild to moderate forms of depression. If the effective strength is not sufficient, they then change to chemical products, which clearly have stronger side effects. St. John’s Wort therapy is well accepted and well documented, with more clinical trials than have been performed for most chemical antidepressants. Over the last 15 years, St. John’s Wort has been taken by approximately 15 million users, most of them under the supervision of a physician. Physicians prescribing St. John’s Wort are usually general practitioners or family doctors, where the persons first go with their problems, and therefore most of the clinical trials were performed in an appropriate setting. In the American Pfizer-organized trial, all the investigators came from psychiatric hospital institutions. The selected patients had suffered from major depression for more than ten years and their current major depressive disorder had already lasted for approximately 2 1/2 years before they entered the St. John’s Wort trial. This clearly indicates the severity of their disease and selection of the wrong study population.

In Germany, this result would not have been found. No German physician would ever treat severe depression with St. John’s Wort. There is even one clinical trial showing that St. John’s Wort is not strong enough for severely depressed patients, yet performs very well on mild to moderate forms of depression.

Generally, the situation in the U.S. for St. John’s Wort is completely different, because it is not a recognized drug, only a dietary supplement, not meant to be used for the treatment of diseases and not accepted by American physicians. A major difference is also the quality control of the products. While this is very strictly regulated in Germany and most other European markets, where St. John’s Wort is registered as drug, there are very large quality differences on the American market.


The Role of the Pharmaceutical Industry


Due to the strong growth of the St. John’s Wort market in Germany, Switzerland and other European countries, several major pharmaceutical companies began to launch St. John’s Wort products. These were usually produced by smaller companies specialized in phytomedicines. Bayer and Novartis are active in several European markets, and Ab­bott/Knoll is active in other parts of the world as well. In the U.S., American Home Products and Bayer have St. John’s Wort products on the market; Warner Lambert did as well, but after the merger with Pfizer, the whole line of botanical products seemed to disappear. It seems to be obvious that Pfizer is trying to set up specific clinical trials in a way that natural products are severely disadvantaged so its main business of chemical products can be expanded. The incorrectly drawn conclusions from this trial, dismissing previous research, generalizing the results from severely depressed patients, etc., leaves many questions open, such as: Was the study initiated for commercial, strategic or at least some scientific reasons in the way it was designed?

The conclusions drawn are unacceptable, not only from the severeness of the disease of the patients, but also from the design, which did not include a chemical antidepressant as a comparison. It is well known and accepted that approximately every third clinical trial with an antidepressant fails to reach significance; this is also the case with stronger acting chemical antidepressants. Having one of several studies with a non-significant result, but showing the same tendency, that St. John’s Wort is effective, would also be a normal situation for any other antidepressant drug.

As an aside, in Europe there are two distinct St. John’s Wort extracts used in most clinical tests. They differ in dosage used (900 mg per day or 500 mg per day), in the level of hypericin standardization (0.3 or 0.2 % hypericin) and in their hyperforin content (high and low). For both extracts, well controlled clinical trials have shown superiority in placebo-controlled as well as comparative trials. Pfizer selected the 0.3% hypericin, hyperforin-rich extract, while—interestingly enough—the European pharmaceutical companies Bayer, Novartis and Abbott/Knoll use the other extract with 0.2% hypericin, practically no hyperforin and only a 500 mg daily dosage. Presently this extract is not available on the American market.

NW

Joerg Gruenwald, Ph.D., is president of Phytopharm Consulting, Institute for Phytopharmaceuticals, a consulting company for herbal medicines and dietary supplements, specialized in international alliances, product and partner findings for new product development and regulatory advice worldwide. He is also the author of the PDR for Herbal Medicines. Dr. Gruenwald can be reached at Waldseeweg 6, D-13467 Berlin, Germany; 49-30 4000 8100, Fax.: 49-30 4000 8400; E-mail: jgruenwald@phytopharm.org; Website: www.phytonet.com.

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