Background: This systematic review evaluated St. John's wort (SJW) for the treatment of Major Depressive Disorder (MDD). The objectives of this review are to (1) evaluate the efficacy and safety of SJW in adults with MDD compared to placebo and active comparator and (2) evaluate whether the effects vary by severity of MDD.
Methods: We searched PubMed, CINAHL, PsycINFO, CENTRAL, Embase, AMED, MANTIS, Web of Science, and ICTRP and existing reviews to November 2014. Two independent reviewers screened the citations, abstracted the data, and assessed the risk of bias. We included randomized controlled trials (RCTs) examining the effect of at least a 4-week administration of SJW on depression outcomes against placebo or active comparator in adults with MDD. Risk of bias was assessed using the Cochrane Risk of Bias tool and USPSTF criteria. Quality of evidence (QoE) was assessed using the GRADE approach.
Results: Thirty-five studies examining 6993 patients met inclusion criteria; eight studies evaluated a hypericum extract that combined 0.3 % hypericin and 1-4 % hyperforin. The herb SJW was associated with more treatment responders than placebo (relative risk [RR] 1.53; 95 % confidence interval [CI] 1.19, 1.97; I(2) 79 %; 18 RCTs; N = 2922, moderate QoE; standardized mean differences [SMD] 0.49; CI 0.23, 0.74; 16 RCTs; I(2) 89 %, N = 2888, moderate QoE). Compared to antidepressants, SJW participants were less likely to experience adverse events (OR 0.67; CI 0.56, 0.81; 11 RCTs; moderate QoE) with no difference in treatment effectiveness (RR 1.01; CI 0.90, 1.14; 17 RCTs, I(2) 52 %, moderate QoE; SMD -0.03; CI -0.21, 0.15; 14 RCTs; I(2) 74 %; N = 2248, moderate QoE) in mild and moderate depression.
Conclusions: SJW monotherapy for mild and moderate depression is superior to placebo in improving depression symptoms and not significantly different from antidepressant medication. However, evidence of heterogeneity and a lack of research on severe depression reduce the quality of the evidence. Adverse events reported in RCTs were comparable to placebo and fewer compared with antidepressants. However, assessments were limited due to poor reporting of adverse events and studies were not designed to assess rare events. Consequently, the findings should be interpreted with caution.
Systematic review registration: PROSPERO CRD42015016406 .
Keywords: Antidepressant; Complementary and alternative medicine; Herb; Major depressive disorder; Meta-analysis; St. John’s wort; Systematic review.