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St. John’s Wort for Depression

St. John's Wort (Hypericum)Objectives: To investigate whether extracts of Hypericum (St. John’s Wort) are more effective than placebo and as effective as standard antidepressants in the treatment of depressive disorders in adults; and whether they have have less side effects than standard antidepressant drugs.

Search strategy: Trials were searched in computerized general (Medline, Embase, Psychlit, Psychindex) and specialized databases (Cochrane Complementary Medicine Field, Cochrane Depression & Neurosis CRG, Phytodok); by checking bibliographies of pertinent articles; and by contacting manufacturers and researchers.

Selection criteria: Trials were included if they: (1) were randomized; (2) included patients with depressive disorders; (3) compared preparations of St. John’s wort (alone or in combination with other plant extracts) with placebo or other antidepressants; and (4) included clinical outcomes such as scales assessing depressive symptoms.

Data collection and analysis: Information on patients, interventions, outcomes and results was extracted by at least two independent reviewers using a standard form. The main outcome measure for comparing the effectiveness of Hypericum with placebo and standard antidepressants was the responder rate ratio (responder rate in treatment group/responder rate in control group). The main outcome measure for side effects was the number of patients reporting side effects.

Main results: 27 trials including a total of 2291 patients met inclusion criteria. 17 trials with 1168 patients were placebo-controlled (16 addressed single preparations, one a combination with four other plant extracts). Ten trials (eight single preparations, two combinations of hypericum and valeriana) with 1123 patients compared hypericum with other antidepressant or sedative drugs. Most trials were four to six weeks long. Participants usually had “neurotic depression” or “mild to moderate severe depressive disorders.”

Hypericum preparations were significantly superior to placebo (rate ratio 2.47; 95% confidence interval 1.69 to 3.61) and similarly effective as standard antidepressants (single preparations 1.01; 0.87 to 1.16, combinations 1.52; 0.78 to 2.94). The proportions of patients reporting side effects were 26.3% for hypericum single preparations vs. 44.7% for standard antidepressants (0.57; 0.47 to 0.69), and 14.6% for combinations vs. 26.5% with amitriptyline or desipramine (0.49; 0.23 to 1.04).

Reviewers’ conclusions: There is evidence that extracts of hypericum are more effective than placebo for the short-term treatment of mild to moderately severe depressive disorders.

The current evidence is inadequate to establish whether hypericum is as effective as other antidepressants.

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Further studies comparing hypericum with standard antidepressants in well defined groups of patients over longer observations periods, investigating long term side effects, and comparing different extracts and doses are needed.

2008 Update

From the Cochrane Collaboration website:

We have reviewed 29 studies in 5489 patients with depression that compared treatment with extracts of St. John’s wort for 4 to 12 weeks with placebo treatment or standard antidepressants. The studies came from a variety of countries, tested several different St. John’s wort extracts, and mostly included patients suffering from mild to moderately severe symptoms.

Overall, the St. John’s wort extracts tested in the trials were superior to placebo, similarly effective as standard antidepressants, and had fewer side effects than standard antidepressants.

However, findings were more favourable to St. John’s wort extracts in studies form Germanā€speaking countries where these products have a long tradition and are often prescribed by physicians, while in studies from other countries St. John’s wort extracts seemed less effective.

This differences could be due to the inclusion of patients with slightly different types of depression, but it cannot be ruled out that some smaller studies from Germanā€speaking countries were flawed and reported overoptimistic results.

Patients suffering from depressive symptoms who wish to use a St. John’s wort product should consult a health professional. Using a St. John’s wort extract might be justified, but important issues should be taken into account: St. John’s wort products available on the market vary to a great extent.

The results of this review apply only to the preparations tested in the studies included, and possibly to extracts with similar characteristics. Side effects of St. John’s wort extracts are usually minor and uncommon. However, the effects of other drugs might be significantly compromised.

St. John’s Wort for Depression

This article has been updated from the original version, which was originally published here on October 12, 2004.

Psych Central Staff

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APA Reference
Psych Central. (2019). St. John’s Wort for Depression. Psych Central. Retrieved on December 3, 2020, from
Scientifically Reviewed
Last updated: 15 May 2019 (Originally: 8 Feb 2015)
Last reviewed: By a member of our scientific advisory board on 15 May 2019
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