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St. John's Wort: Future Treatment for Obsessive-Compulsive Disorder?

A small, open clinical study suggests that St. John's wort (SJW) warrants further study as a treatment for obsessive-compulsive disorder (OCD), an anxiety disorder characterized by repetitive behaviors and/or thoughts (Taylor et al., 2000). Numerous studies have shown that St. John's wort (Hypericum perforatum L., Clusiaceae) is effective in alleviating mild to moderate depression, possibly via effects on the brain's uptake of the neurotransmitter serotonin. Recently, studies have shown that serotonin-reuptake inhibitors (SRI) antidepressant drugs (including clomipramine, fluoxetine, fluvoxamine, paroxetine, and sertraline) are effective against OCD, leading researchers to speculate about the potential of SJW as a new treatment for the condition.

For the open-label study, the researchers enrolled 13 people who had been diagnosed with OCD at least 12 months earlier. (One subsequently dropped out because of a rash.) Participants received 450 mg SJW (standardized to 0.3 percent hypericin) twice daily for 12 weeks. (The authors provided no further details about the SJW preparation used.) At baseline and one-week intervals thereafter, clinicians evaluated the participants using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression of Improvement Scale (CGI). Participants evaluated their own improvement using the CGI. At baseline and one-month intervals, changes in depression were measured using the Hamilton Rating Scale for Depression (HAM-D).

At endpoint (after 12 weeks or at the time the subject left the study), participants had an average drop of 7.4 points on the Y-BOCS. On the CGI scale, clinicians rated 42 percent of participants as "much" or "very much improved," 50 percent as "minimally improved," and 8 percent (one person) as unchanged. Participants' self-evaluations yielded identical assessments. By all three of these outcome measures, SJW had a highly significant beneficial effect - comparable to that observed with clomipramine, other SRIs, and behavior therapy. Participants' mean HAM-D scores also dropped significantly between baseline and endpoint, although the authors noted that participants began the trial with scores that did not indicate clinical depression.

SJW generally takes four to six weeks to exert an antidepressant effect. Because a statistically significant change in Y-BOCS scores was noted after only one week of treatment in the OCD trial, the researchers suspect that a placebo effect may have accounted for the dramatic improvement observed. However, the treatment effect continued to increase over time, whereas a genuine placebo effect typically diminishes. Future placebo-controlled, double-blind studies are needed to resolve this question. Adverse events included diarrhea (reported by three participants) and restless sleep (in two participants). One dropped out in the first days of the study because of a rash, leaving 12 participants. The prescription drugs used to treat OCD generally have more serious and frequent side effects, so larger studies supporting this new indication for SJW could be welcome news to people affected by the disorder.

Although SJW's primary mechanism of action remains undetermined, laboratory research indicates that the herb inhibits the uptake of other brain chemicals (dopamine and norepinephrine) as effectively as it acts on serotonin. Most SRIs are more selective in their mode of action, primarily blocking serotonin. Interestingly, the SRI that appears most effective against OCD, clomipramine, is also the least serotonin-specific. It is possible that SJW, too, exerts its effect by acting on a broader group of neurotransmitters.

- Nancy Hoegler, Herb Research Foundation [Taylor LvH, Kobak K. An open-label trial of St. John's wort (Hypericum perforatum) in obsessive-compulsive disorder. Journal of Clinical Psychiatry 2000; 61(8): 575-578.]

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