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St. John's Wort Equivalent to World's Best-selling Antidepressant

St. John's wort (Hypericum perforatum L., Clusiaceae) is one of the world's best-researched phytomedicines. One criticism from the medical community, however, has been that most of the clinical research on St. John's wort (SJW) has matched it against the tricyclic antidepressants, rather than newer, more commonly used agents. It should be noted that during the time at which most SJW research was conducted, doctors favored the tricyclic antidepressants. Now, physicians claim that in order for research results to be truly meaningful, SJW must be compared with selective serotonin reuptake inhibitor (SSRI) antidepressants.

The latest clinical trial investigating the antidepressant effects of SJW does just that, by comparing it to fluoxetine (Prozac®) - the world's best selling antidepressant (Schrader, 2000). This German study was funded not by a pharmaceutical company, or by a company that manufacturers SJW extract, but by the German medical insurance system. The results were impressive. The study concluded, "…the two treatments are essentially equipotent in their antidepressant effects." Furthermore, the researchers asserted that there was "…no evidence to suggest an advantage in treating these patients with fluoxetine."

The randomized, double-blind, six-week study involved 240 outpatients from seven different internal medicine practices. One hundred and fourteen participants took fluoxetine at a dose of 20 mg twice daily; 128 took hypericum extract at a dose of 250 mg twice daily. The hypericum extract used in the study (Ze 117, Zeller AG, Switzerland) was a 50 percent ethanolic extract with an herb to extract ratio of 4-7:1. All patients were evaluated by psychiatrists using the Hamilton Depression Scale (HAM-D), a standard test used to evaluate symptoms of depression.

After six weeks of treatment, improvement in the two groups was nearly identical. Beginning with mean HAM-D scores of 19.5 and 19.65 for the fluoxetine and hypericum groups, respectively, at endpoint the two groups had scores of 12.2 and 11.54, respectively. The results were also virtually identical for sub-scores of the depression index. For example, the depression sub-score (4.0 vs. 3.7) and anxiety sub-score (2.7 vs. 2.5.) for SJW and Prozac, respectively, were deemed equivalent, as measured by the latest scientific research model, using what pharmaceutical science considers the best treatment for depression.

Perhaps more importantly, however, safety as measured by this study was far superior for SJW, which caused consistently fewer and less serious side effects. Of all the side effects reported in the study, 72 percent were reported by the fluoxetine group, and only 28 percent by the SJW group. In addition, side effects were much more serious in the fluoxetine group, and included "retching, dizziness, tiredness, anxiety-associated symptoms, and erectile dysfunction." The only significant side effect seen with SJW was gastrointestinal upset, but according to the researchers, this was "mild and did not compromise the efficacy or patient compliance."

On the other hand, the seriousness of side effects with fluoxetine "may have reduced the magnitude of its beneficial effects. Unlike severely depressed patients, those mildly affected are less tolerant of side effects of antidepressants." In fact, the authors pointed out that "patients with mild illnesses are often reluctant to accept treatments that cause side-effects that are as upsetting as the symptoms of their underlying disease." This may be reflected in the dramatic difference in "responder rate" in the study, which was 60 percent in the SJW group and only 40 percent among those taking fluoxetine. "Responders" were defined as those who had a reduction of 50 percent or more in depression score.

The authors summarize the results of this study in a way that clearly outlines the superiority of SJW as the medication of choice for mild to moderate depression. They noted, "A clear advantage of hypericum over fluoxetine with regard to safety seems incontrovertible, whether one considers the overall incidence of side-effects, the number of patients reporting events, or the type of event. The one type of event reported on hypericum, GI disturbance, is still less frequently reported for this treatment than for the synthetic antidepressant. When treating patients with mild to moderate depression, hypericum (in the form of St. John's wort Ze 117 extract tablet) should be considered as one of the first treatment options based upon both efficacy and safety, particularly in cases where treatment is a choice between fluoxetine and hypericum."
The SJW extract used as the test substance is standardized, but this detail was omitted from the research publication. Ze 117 is standardized to 0.5 mg hypericin per 250 mg tablet, according to the manufacturer's CEO (Hasler, 2000). - Rob McCaleb, HRF

[Hasler A. July 12, 2000. Personal communication.
Schrader E. Equivalence of a St. John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. International Clinical Psychopharmacology 2000; 15(2): 61-68.]

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