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Review
. 2008 Oct 8;2008(4):CD000448.
doi: 10.1002/14651858.CD000448.pub3.

St John's Wort for Major Depression

Affiliations
Free PMC article
Review

St John's Wort for Major Depression

Klaus Linde et al. Cochrane Database Syst Rev. .
Free PMC article

Abstract

Background: In some countries extracts of the plant Hypericum perforatum L. (popularly called St. John's wort) are widely used for treating patients with depressive symptoms.

Objectives: To investigate whether extracts of hypericum are more effective than placebo and as effective as standard antidepressants in the treatment of major depression; and whether they have fewer adverse effects than standard antidepressant drugs.

Search strategy: Trials were searched in computerised databases, by checking bibliographies of relevant articles, and by contacting manufacturers and researchers.

Selection criteria: Trials were included if they: (1) were randomised and double-blind; (2) included patients with major depression; (3) compared extracts of St. John's wort with placebo or standard antidepressants; (4) included clinical outcomes assessing depressive symptoms.

Data collection and analysis: At least two independent reviewers extracted information from study reports. The main outcome measure for assessing effectiveness was the responder rate ratio (the relative risk of having a response to treatment). The main outcome measure for adverse effects was the number of patients dropping out due to adverse effects.

Main results: A total of 29 trials (5489 patients) including 18 comparisons with placebo and 17 comparisons with synthetic standard antidepressants met the inclusion criteria. Results of placebo-controlled trials showed marked heterogeneity. In nine larger trials the combined response rate ratio (RR) for hypericum extracts compared with placebo was 1.28 (95% confidence interval (CI), 1.10 to 1.49) and from nine smaller trials was 1.87 (95% CI, 1.22 to 2.87). Results of trials comparing hypericum extracts and standard antidepressants were statistically homogeneous. Compared with tri- or tetracyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs), respectively, RRs were 1.02 (95% CI, 0.90 to 1.15; 5 trials) and 1.00 (95% CI, 0.90 to 1.11; 12 trials). Both in placebo-controlled trials and in comparisons with standard antidepressants, trials from German-speaking countries reported findings more favourable to hypericum. Patients given hypericum extracts dropped out of trials due to adverse effects less frequently than those given older antidepressants (odds ratio (OR) 0.24; 95% CI, 0.13 to 0.46) or SSRIs (OR 0.53, 95% CI, 0.34-0.83).

Authors' conclusions: The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.

Conflict of interest statement

Michael Berner has received a grant for research on hypericum in the past and has received fees for speaking on conferences from a manufacturer (Schwabe). Klaus Linde once received reimbursement for travel expenses for speaking on a meeting organised by a manufacturer (Schwabe). Levente Kriston once received reimbursement for travel expenses (Schwabe).

Figures

1
1
Forest plot of comparison: 1 Hypericum mono‐preparations vs. placebo A. Dichotomous measures, outcome: 1.1 Responder ‐ grouped by precision ‐ primary analysis.
2
2
Forest plot of comparison: 1 Hypericum mono‐preparations vs. placebo A. Dichotomous measures, outcome: 1.5 Responder among studies from German‐speaking countries and other studies.
3
3
Funnel plot of comparison: 1 Hypericum mono‐preparations vs. placebo A. Dichotomous measures, outcome: 1.1 Responder ‐ grouped by precision ‐ primary analysis.
4
4
Forest plot of comparison: 4 Hypericum mono‐preparations vs. standard antidepressants. A. Dichotomous measures, outcome: 4.1 Responder (intent to treat) ‐ primary analysis.
5
5
Forest plot of comparison: 4 Hypericum mono‐preparations vs. standard antidepressants. A. Dichotomous measures, outcome: 4.4 Responder among studies from German‐speaking studies and other studies.
6
6
Funnel plot of comparison: 4 Hypericum mono‐preparations vs. standard antidepressants. A. Dichotomous measures, outcome: 4.1 Responder (intent to treat) ‐ primary analysis.
7
7
Forest plot of comparison: 6 Safety ‐ Hypericum mono‐preparations vs. standard antidepressants, outcome: 6.1 Number of patients discontinuing treatment/dropping out due to adverse/side effects.
1.1
1.1. Analysis
Comparison 1 Hypericum mono‐preparations vs. placebo A. Dichotomous measures, Outcome 1 Responder ‐ grouped by precision ‐ primary analysis.
1.2
1.2. Analysis
Comparison 1 Hypericum mono‐preparations vs. placebo A. Dichotomous measures, Outcome 2 Responder ‐ according to HAMD.
1.3
1.3. Analysis
Comparison 1 Hypericum mono‐preparations vs. placebo A. Dichotomous measures, Outcome 3 Responder ‐ according to CGI (Clinical Global Impression Index at least "much improved").
1.4
1.4. Analysis
Comparison 1 Hypericum mono‐preparations vs. placebo A. Dichotomous measures, Outcome 4 Responder ‐ grouped by extract.
1.5
1.5. Analysis
Comparison 1 Hypericum mono‐preparations vs. placebo A. Dichotomous measures, Outcome 5 Responder among studies from German‐speaking countries and other studies.
1.6
1.6. Analysis
Comparison 1 Hypericum mono‐preparations vs. placebo A. Dichotomous measures, Outcome 6 Remission (HAMD score < 8 or < 7).
2.1
2.1. Analysis
Comparison 2 Hypericum mono‐preparations vs. placebo. B. Continuous measures, Outcome 1 Mean HAMD (Hamilton Rating Scale for Depression) scores after therapy.
2.2
2.2. Analysis
Comparison 2 Hypericum mono‐preparations vs. placebo. B. Continuous measures, Outcome 2 Mean HAMD (Hamilton Rating Scale for Depression) scores after 2 to 3 weeks of treatment.
2.3
2.3. Analysis
Comparison 2 Hypericum mono‐preparations vs. placebo. B. Continuous measures, Outcome 3 Mean HAMD (Hamilton Rating Scale for Depression) score after 4 weeks of treatment.
2.4
2.4. Analysis
Comparison 2 Hypericum mono‐preparations vs. placebo. B. Continuous measures, Outcome 4 Mean HAMD (Hamilton Rating Scale for Depression) scores after 6 to 8 weeks of treatment.
2.5
2.5. Analysis
Comparison 2 Hypericum mono‐preparations vs. placebo. B. Continuous measures, Outcome 5 Difference HAMD (Hamilton Rating Scale for Depression) baseline ‐ end of treatment.
2.6
2.6. Analysis
Comparison 2 Hypericum mono‐preparations vs. placebo. B. Continuous measures, Outcome 6 MADRS after treatment.
2.7
2.7. Analysis
Comparison 2 Hypericum mono‐preparations vs. placebo. B. Continuous measures, Outcome 7 Difference MADRS baseline ‐ end of treatment.
2.8
2.8. Analysis
Comparison 2 Hypericum mono‐preparations vs. placebo. B. Continuous measures, Outcome 8 Mean HAMD after treatment in studies from German‐speaking countries and other studies.
2.9
2.9. Analysis
Comparison 2 Hypericum mono‐preparations vs. placebo. B. Continuous measures, Outcome 9 Mean Depression Scale von Zerssen (D‐S) after therapy/difference baseline ‐ after therapy.
2.10
2.10. Analysis
Comparison 2 Hypericum mono‐preparations vs. placebo. B. Continuous measures, Outcome 10 Various self‐rating scales.
2.11
2.11. Analysis
Comparison 2 Hypericum mono‐preparations vs. placebo. B. Continuous measures, Outcome 11 Various self‐rating scales in studies from German‐speaking countries and other countries.
3.1
3.1. Analysis
Comparison 3 Safety ‐ Hypericum mono‐preparations vs. placebo, Outcome 1 Number of patients discontinuing treatment/dropping out for adverse effects ‐ primary analysis.
3.2
3.2. Analysis
Comparison 3 Safety ‐ Hypericum mono‐preparations vs. placebo, Outcome 2 Number of patients dropping out.
3.3
3.3. Analysis
Comparison 3 Safety ‐ Hypericum mono‐preparations vs. placebo, Outcome 3 Number of patients reporting adverse effects.
4.1
4.1. Analysis
Comparison 4 Hypericum mono‐preparations vs. standard antidepressants. A. Dichotomous measures, Outcome 1 Responder (intent to treat) ‐ primary analysis.
4.2
4.2. Analysis
Comparison 4 Hypericum mono‐preparations vs. standard antidepressants. A. Dichotomous measures, Outcome 2 Responder (per protocol).
4.3
4.3. Analysis
Comparison 4 Hypericum mono‐preparations vs. standard antidepressants. A. Dichotomous measures, Outcome 3 Responders according to CGI (Clinical Global Impression Index at least "much improved").
4.4
4.4. Analysis
Comparison 4 Hypericum mono‐preparations vs. standard antidepressants. A. Dichotomous measures, Outcome 4 Responder among studies from German‐speaking studies and other studies.
4.5
4.5. Analysis
Comparison 4 Hypericum mono‐preparations vs. standard antidepressants. A. Dichotomous measures, Outcome 5 Remission (HAMD score < 8).
5.1
5.1. Analysis
Comparison 5 Hypericum mono‐preparations vs. standard antidepressants. B. Continuous measures, Outcome 1 Mean HAMD (Hamilton Rating Scale for Depression) after therapy.
5.2
5.2. Analysis
Comparison 5 Hypericum mono‐preparations vs. standard antidepressants. B. Continuous measures, Outcome 2 Mean HAMD (Hamilton Rating Scale for Depression) scores after 2 or 3 weeks of treatment.
5.3
5.3. Analysis
Comparison 5 Hypericum mono‐preparations vs. standard antidepressants. B. Continuous measures, Outcome 3 Mean HAMD (Hamilton Rating Scale for Depression) scores after 4 weeks of treatment.
5.4
5.4. Analysis
Comparison 5 Hypericum mono‐preparations vs. standard antidepressants. B. Continuous measures, Outcome 4 Mean HAMD (Hamilton Rating Scale for Depression) scores after 6 to 8 weeks of treatment.
5.5
5.5. Analysis
Comparison 5 Hypericum mono‐preparations vs. standard antidepressants. B. Continuous measures, Outcome 5 Difference HAMD (Hamilton Rating Scale for Depression) baseline ‐ end of treatment.
5.6
5.6. Analysis
Comparison 5 Hypericum mono‐preparations vs. standard antidepressants. B. Continuous measures, Outcome 6 MADRS after treatment.
5.7
5.7. Analysis
Comparison 5 Hypericum mono‐preparations vs. standard antidepressants. B. Continuous measures, Outcome 7 Difference MADRS baseline ‐ end of treatment.
5.8
5.8. Analysis
Comparison 5 Hypericum mono‐preparations vs. standard antidepressants. B. Continuous measures, Outcome 8 Mean HAMD after treatment in studies from German‐speaking countries and other studies.
5.9
5.9. Analysis
Comparison 5 Hypericum mono‐preparations vs. standard antidepressants. B. Continuous measures, Outcome 9 Mean D‐S (Depression Scale von Zerssen) scores after therapy.
5.10
5.10. Analysis
Comparison 5 Hypericum mono‐preparations vs. standard antidepressants. B. Continuous measures, Outcome 10 Various self‐rating scales.
5.11
5.11. Analysis
Comparison 5 Hypericum mono‐preparations vs. standard antidepressants. B. Continuous measures, Outcome 11 Various self‐rating scales in studies from German‐speaking countries and other countries.
6.1
6.1. Analysis
Comparison 6 Safety ‐ Hypericum mono‐preparations vs. standard antidepressants, Outcome 1 Number of patients discontinuing treatment/dropping out due to adverse/side effects.
6.2
6.2. Analysis
Comparison 6 Safety ‐ Hypericum mono‐preparations vs. standard antidepressants, Outcome 2 Number of patients dropping out.
6.3
6.3. Analysis
Comparison 6 Safety ‐ Hypericum mono‐preparations vs. standard antidepressants, Outcome 3 Number of patients reporting adverse effects.

Update of

  • St John's wort for depression.
    Linde K, Mulrow CD, Berner M, Egger M. Linde K, et al. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD000448. doi: 10.1002/14651858.CD000448.pub2. Cochrane Database Syst Rev. 2005. PMID: 15846605 Updated. Review.

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