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Three Concentrations of St. John's Wort Effective Against Depression

At least 25 double-blind clinical studies have established the efficacy of St. John's wort (Hypericum perforatum L., Clusiaceae) in treating mild-to-moderate depression. In a recent double-blind, multicenter study, Swiss researchers took off in a different direction. They attempted to determine the optimum dosage of hypericin, a constituent that is thought to play an important role in the plant's antidepressant activity (Lenoir et al., 1999). Researchers compared the effect of three different concentrations of St. John's wort (SJW) in 348 depressed individuals over a six-week period. The study included the concentration used in clinical studies and commercial products (0.33 mg total hypericin per day), as well as extracts with lower and higher hypericin content. At the end of the trial, all three treatment groups demonstrated significant improvement, with no major differences between the groups. Researchers did not measure the effects of other potentially important compounds in the SJW extracts, such as hyperforin.

Volunteers for the study were recruited from 38 centers in Germany and Switzerland. Participants took three tablets of SJW daily (Hyperiforce, manufactured by Bioforce AG, Switzerland), standardized to either 0.17 mg, 0.33 mg, or 1 mg total hypericin per day. The range of hypericin tested in the study was based on monographs published by Germany's Commission E and the European Scientific Cooperative for Phytotherapy (ESCOP), which recommend a range of 0.2 mg to 1.0 mg of hypericin daily. This study did not include a placebo group, both for ethical reasons and because previous placebo-controlled studies have established the plant's overall efficacy. Researchers measured improvement using the Hamilton Psychiatric Rating Scale for Depression (HAMD-17), self-assessments from patients (Hospital Anxiety and Depression Scale), and physician assessments (Clinical Global Impression Scale).

At the end of the six-week study, HAMD scores decreased to a significant degree, by roughly 50 percent in all three treatment groups with little difference between dose levels. The HAMD measures a reduction in symptoms such as depressive mood, insomnia, fatigue, anxiety, and inability to perform daily tasks. Physicians rated the efficacy of SJW "moderate to good" in roughly 70 percent of cases for all of the groups. Self-assessments by patients supported these results. Seventy-four patients reported a total of 82 mild side effects during the course of the study; however, only seven were causally linked to SJW. The most common complaints were nausea, headache, and dizziness, and there was no difference in the overall incidence between groups. There were 88 dropouts from the study due to lack of compliance, medical reasons, or other causes.

The overall response rate in this study was 62 to 68 percent, which is higher than the average 55 percent response rate the authors found in the 13 placebo-controlled studies they analyzed for their study. The authors suggested that their results might be due to the specific extract used in this study - a preparation made from the fresh tips of SJW shoots, which are thought to yield a higher concentration of hypericin than whole plant extracts. On the other hand, the study only considered hypericin content, leaving many unanswered questions about the range of different compounds that may be important to SJW's antidepressant activity. The lack of a dose-response effect in this trial with SJW standardized for hypericin content may provide support for the theory that hypericin is not the main active constituent for the relief of mild-to-moderate depression. - Krista Morien, HRF

[Lenoir S, Degenring FH, Saller R. A double-blind randomised trial to investigate three different concentrations of a standardised fresh plant extract obtained from the shoot tips of Hypericum perforatum L. Phytomedicine 1999; 6(3): 141-146.]

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