This review assessed the efficacy and tolerability of Hypericum perforatum against selective serotonin reuptake inhibitors for the treatment of major depressive disorder and concluding that there was no difference in outcomes, except for lower withdrawal rates for Hypericum due to adverse events. The authors' conclusions accurately reflected the evidence presented and are likely to be reliable.

To assess the efficacy and tolerability of Hypericum perforatum versus selective serotonin reuptake inhibitors (SSRIs) for the treatment of major depressive disorder.

PubMed, EMBASE, Scopus, Web of Science and Cochrane Central Register of Controlled Trials were searched with no language or publication restrictions from inception to June 2008; search terms were reported. The reference lists of included studies were searched to identify additional studies.

Controlled trials in patients with major depressive disorder that compared Hypericum with SSRIs in oral formulations were eligible for inclusion; major depressive disorder diagnosis was according to DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) or ICD-10 (International Statistical Classification of Diseases and Related Health Problems 10th Revision).

Studies were excluded if Hypericum was compared only with placebo or if outcomes did not relate to efficacy or tolerability. Included SSRIs comprised: fluoxetin, fluoxetine, citalopram and sertraline; the most frequent comparison was with fluoxetine. In included studies Hypericum dose ranged from 20mg to 1,800mg per day and SSRI dose from 20 mg to 100mg per day. Outcomes included: clinical response; remission; total adverse events; withdrawals due to adverse events; and mean reduction in Hamilton Rating Scale for Depression score from baseline. Mean patient age, where stated, ranged from 37.3 to 69 years. Depression severity ranged from mild to severe. In the included trials, treatment duration was from four to 12 weeks.

Three reviewers independently selected the studies for inclusion; there were no disagreements.

Methodological quality was assessed using the Jadad scale, a 5-point scale evaluating randomisation, blinding and withdrawals; studies were considered high quality if they scored 3 points or more. The authors did not state how the validity assessment was performed.

Three reviewers independently extracted the data; there were no disagreements. For each study relative risks (RRs) were calculated for dichotomous outcomes and mean differences for continuous data (based on change from baseline scores), with associated 95% confidence intervals (CI).

Pooled RRs and weighted mean differences (WMD) were calculated with 95% CIs. Random-effects models were used where significant heterogeneity was present and fixed-effects models where it was absent. Statistical heterogeneity was assessed using the Cochran Q test and explored using L’Abbe plots. Publication bias was assessed by funnel plots.

A total of 13 RCTs were included in the review (n at least 1,754; some trials did not clearly report the number randomised; range 30 to 258). Five studies obtained a Jadad score of 3, four studies scored 4 and three studies scored 5.

There was no significant difference between comparisons for the main effectiveness outcomes (clinical response, remission, mean reduction in Hamilton Rating Scale for Depression score from baseline and any adverse events). Compared with SSRIs, Hypericum yielded a significantly fewer withdrawals due to adverse events (RR 0.53, 95% CI 0.35 to 0.82; 11 studies); there was no significant heterogeneity for this comparison.

In patients with major depressive disorder, there was no difference in outcomes between Hypericum and SSRIs with the exception of lower withdrawal rates for Hypericum due to adverse events.

The review question and inclusion criteria were clear. The search strategy consulted a number of relevant sources; no language or publication restrictions were placed upon the search, which reduced the potential for language and publication biases. All stages of the review process were undertaken in triplicate, which reduced the potential for error and bias. Appropriate criteria were used to assess the quality of the included studies, although just under half achieved a score of 3 or less (out of 5). Suitable methods were used for the meta-analysis. Heterogeneity was assessed and found to be absent from the analysis for the significant outcome. The authors stated that an assessment of publication bias was undertaken, but this was not reported in the review. The potential for interactions with other drugs was not addressed by the review. Generally this was a well-conducted review, although the findings may have been compromised by a lack of good quality data and clinical heterogeneity; despite this the authors' conclusions accurately reflected the evidence presented and are likely to be reliable.

The authors did not state any implications for practice or further research.

None.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.