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St. John's wort for depression.

The Problem

You have a patient who suffers with depression. He is not interested in taking synthetic antidepressants, but asks you about St. John's wort.

The Question

Is St. John's wort efficacious for the treatment of depression?

The Analysis

We searched the Cochrane Database of Systematic Reviews ( and discovered a review that was last assessed as being up to date on Aug. 7, 2008 (Cochrane Database Syst. Rev.2008;doi:10.1002/ 14 6 5 18 5 8. CD000448.pub3.

The Evidence

Hypericum perforatum L. (St. John's wort or Klamath weed) is a weedy, invasive plant that grows in most states, many of which classify it as a "noxious weed" (

For inclusion in this Cochrane review, studies had to be double blind, randomized, and of at least 4 weeks' duration. Patients had to meet criteria for major depressive disorder according to DSM-IV or ICD-10 criteria.

The main comparisons were hypericum vs. placebo and hypericum vs. synthetic antidepressants. Most trials measured outcomes using the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions (CGI) scale. The HAM-D focuses mainly on somatic symptoms of depression. The 17-item scale was most commonly used, with a total score of 0-54. (The 2.1-item version measures additional symptoms of depression, such as obsession or paranoia.) Most studies using the HAM-D defined treatment responders as patients who reach a score of less than 10 and/or less than 50% of the baseline score.

The CGI scale looks at three items (illness severity, global improvement, and efficacy index) and assigns a score of 1-7 to each item. The HAM-D and the CGI are observer rated. The most frequently used patient-rated scale was the von Zerssen Depression Scale (DS), a 16-item scale that looks at depressive symptoms and dysphoria.

For this review, 29 trials with a total of 5,489 patients (range, 30-388) were included; among them, 18 studies had a placebo control group, 17 compared hypericum with synthetic antidepressants, and 6 had both a placebo and standard antidepressant control group. Trials occurred in Germany, Switzerland, Austria, the United States, the United Kingdom, Brazil, Canada, Denmark, France, and Sweden.

Studies used daily doses of hypericum extract between 240 mg and 1,800 mg (mostly 500-1,200 mg). The synthetic antidepressants used were fluoxetine (six trials, 20-40 mg/day), sertraline (four trials, 50-100 mg/day), imipramine (three trials, 100-150 mg/day), citalopram (one trial, 20 mg/day), paroxetine (one trial, 20-40 mg/day), maprotiline (one trial, 75 mg/day), and amitriptyline (one trial, 75 mg/day).

When compared with placebo, patients receiving hypericum were significantly more likely to respond (relative risk, 1.48). The Cochrane reviewers noted that "more precise trials" had a less profound effect (RR, 1.28) when compared with "less precise trials" (RR, 1.87). Trials in German-speaking countries reported more positive results than did trials from other countries. Six trials reported remission rates significantly higher than placebo (RR, 2.77). The number of patients dropping out because of adverse effects was similar between the hypericum and placebo groups (odds ratio, 0.92).

Studies that compared hypericum to synthetic antidepressants all used the HAM-D to measure response. Overall, hypericum was as effective as synthetic antidepressants (RR, 1.01). When hypericum was compared with older antidepressants, the relative risk was 1.02. When it was compared with selective serotonin reuptake inhibitors in 12 trials, it was 1.00. Again, trials in German-speaking countries reported higher response rates with hypericum (RR, 1.04). The number of patients who dropped out because of adverse effects was lower in the hypericum group, when compared with older antidepressants (OR, 0.24) or SSRIs (OR, 0.53).

The Conclusion

The best available evidence suggests that St. John's wort is better than placebo for treating major depressive disorder, is as effective as some synthetic antidepressants when used in low to moderate dosing ranges, and has fewer side effects than do synthetic antidepressants.

The Food and Drug Administration does not strictly regulate herbs. There is no guarantee of strength, purity, or safety of products ( and Martindale's drug reference lists over 300 preparations, so there can be considerable variability in efficacy between preparations ( Hypericum can cause side effects similar to those from synthetic antidepressants, including mania induction and suicidal or homicidal thoughts. It interacts with the cytochrome P450 enzyme system, causing increased serum levels of medications such as carbamazepine, cyclosporine, midazolam, nifedipine, simvastatin, theophylline, warfarin, or HIV medications. Also, taking hypericum with synthetic antidepressants can cause serotonin syndrome. St. John's wort can interact with other herbal supplements such as valerian (a sedative herb), causing confusion and agitation (



Dr. Leard-Hansson is a forensic psychiatrist who practices in San Diego. Dr. Guttmacher is chief of psychiatry at the Rochester (N. Y.) Psychiatric Center. They have no financial interest in any product or service discussed in this column.
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Author:Leard-Hansson, Jan; Guttmacher, Laurence
Publication:Clinical Psychiatry News
Date:Dec 1, 2008
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