The treatment of minor depression with St. John's Wort or citalopram: failure to show benefit over placebo.

The short version

This randomized, double-blind, placebo-controlled trial with 81 randomized adults explored whether St. John's wort, a widely used herbal remedy, or the antidepressant citalopram works better than a dummy pill for minor depression. Minor depression means having two to four depressive symptoms, such as low mood or loss of interest, for months without meeting the criteria for major depression. It is common, yet few treatments have been shown to help it, and an earlier study of the antidepressant fluoxetine had found benefit mainly in its most severely ill participants. The researchers also wanted to learn how many side effects people already report before taking any study pill. Participants were recruited at three US medical centers through clinical referrals and community advertising. They took St. John's wort 810 mg a day, citalopram 20 mg a day, or look-alike placebo for 12 weeks, without knowing which. Depression severity was rated by clinicians on the 30-item Inventory of Depressive Symptomatology, alongside quality-of-life, well-being and side-effect questionnaires completed at visits every two weeks. Seventy-three people had at least one follow-up visit and 59 finished the trial. Neither treatment beat placebo. On the main depression score the difference between groups was negligible (p = 0.771), and 52.2% of placebo participants improved by at least half, compared with 41.7% on citalopram and 38.5% on St. John's wort (meaning the dummy pill did at least as well as either active treatment). Quality of life and well-being followed the same pattern. Side effects were common in every group: about 60% of people reported symptoms that looked like side effects before taking anything, and 85% of the St. John's wort group, 100% of the citalopram group and 91% of the placebo group reported new or worsening problems during treatment. Distressing side effects reached 35%, 60% and 39% respectively, and stomach and sleep problems were more frequent with both active treatments than with placebo. The authors attribute the result to a large placebo response and suggest that brief non-drug approaches deserve study for minor depression. Limitations include a modest sample that fell short of the planned size, a St. John's wort group that was younger than the others and no blood tests to confirm that participants took the product. The findings concern one St. John's wort preparation at one dose in minor depression only, and do not extend to major depression.

Key findings

• In this 12-week double-blind trial, 81 adults with minor depression (a milder form of depression with two to four symptoms) were randomized to St. John's wort 810 mg a day, citalopram 20 mg a day or placebo; 73 were evaluable.
• Neither treatment beat placebo on the main depression score (IDS-C30 treatment-by-time p = 0.771); at least 50% improvement occurred in 52.2% of placebo, 41.7% of citalopram and 38.5% of St. John's wort participants.
• Quality of life and psychological well-being also did not differ, which the authors attribute to a consistently large placebo response rather than too small a sample.
• About 60% of participants reported side-effect-like symptoms before taking any study pill, and new or worsening side effects were reported by 84.6% (St. John's wort), 100% (citalopram) and 91.3% (placebo), reaching a distressing level in 34.6%, 60.0% and 39.1%.
• The authors note the modest sample, a younger St. John's wort group and unverified adherence, and the result concerns one St. John's wort product and dose in minor depression only.

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