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The Effectiveness of St. John's Wort

Searchable question: For an adult male, how does St. John’s wort compare to prescription antidepressants for the treatment of depression?

  • P: Adult male
  • I: St. John’s wort (Hypericum perforatum)
  • C: Prescription antidepressants
  • O: Relative efficacy

Evidence based answer: St. John’s Wort is effective in treating mild to moderate depression. It is as efficacious as citalopram, sertraline, and imipramine. It is potentially more efficacious than paroxetine and fluoxetine.

Evidence summary: Depression is quantified by a number of questionnaires, the most common being the Hamilton Rating Scale for Depression (HAMD) with 17 items contributing to the severity of the episode. A higher score indicates a more severe depression. The changes in HAM-D scores from baseline to the end of the study are used to indicate efficacy of a therapy.

After six weeks of treatment, mean +/- standard deviation decreases in HAMD total scores of 11.6 +/- 6.4 for 600 mg/day St. John’s Wort, 10.8 +/- 7.3 for 1200 mg/day St. John’s Wort, and 6.0 +/- 8.1 for placebo were observed^1. Secondary measures of treatment efficacy also showed that both St. John’s Wort groups were statistically superior to placebo.

St. John’s Wort has demonstrated antidepressant efficacy when compared to placebo, but comparisons with other antidepressants remain controversial.

In a study comparing St. John’s Wort 600mg/day, citalopram 20mg/day, and placebo for 6 weeks with a participant base of roughly 150 per group, HAM-D (17 items) decreased by 11.6, 11.5, and 9.0, respectively. This illustrates the relative equivalence between St. John’s Wort and citalopram in treating mild to moderate depression, and the superiority of both therapies over placebo^3.

In a study comparing St. John’s Wort to sertraline with roughly 125 participants in each group, it was shown that once daily administration of 612mg St. John’s Wort and 50mg sertraline were at least as effective as each other. After the first 12-week treatment period, the HAM-D scores decreased by 13.7 and 14.0, respectively. A statistical test for non-inferiority revealed that hypericum extract is not inferior to sertraline^4.

In a study comparing St. John’s Wort to paroxetine with roughly 125 participants in each group, it is shown that 900mg three times a day of hypericum is superior to 20mg once a day of paroxetine over six weeks of treatment. The hypericum group’s HAMD scores decreased by 14.4 compared to 11.3 points achieved in the paroxetine group^5.

In a study comparing St. John’s Wort to imipramine with roughly 175 participants in each group, 250 mg twice daily of hypericum is as effective as 75 mg twice daily of imipramine in the 6-week study. A decrease in HAMD scores of 10.4 in the hypericum group and 8.4 in the imipramine group indicates the relative effectiveness of hypericum^8.

In a study comparing St. John’s Wort to fluoxetine with roughly 50 participants in each group, 900mg/day of hypericum is as effective as fluoxetine 20mg/day over a 12-week study in treating a major depressive episode. A decrease in HAMD scores of 9.5 for the hypericum group and 6.4 for the fluoxetine group indicates hypericum is an effective treatment for major depressive episodes, compared with fluoxetine^7.

The studies listed above illustrate the superior effectiveness of hypericum compared to placebo, and the relative efficacies compared to the specified antidepressants. The above studies ranged in duration from 6-12 weeks, with a daily hypericum dosage of 500mg-2700mg. In every study, hypericum was better tolerated than other treatments (placebo toleration was not reported), indicating it was a safer therapy.

Recommendations from others:

The recommended dose of St. John’s Wort is 500-2700mg/day for the treatment of mild to moderate depressive episodes, with some evidence suggesting efficacy in treating major depressive episodes.

By Joey Sweeney
Doctor of Pharmacy Candidate 2009

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