A Cautious Thumbs-Up for St. John’s Wort


Is St. John’s wort (SJW; Hypericum perforatum) an appropriate treatment option for patients with MDD? What advice should be given to patients who inquire about it?

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Is St. John’s wort (SJW; Hypericum perforatum) an appropriate treatment option for patients with MDD? What advice should be given to patients who inquire about it?

The most recent efficacy and safety findings, authored by a team from the Rand Corporation and initially prepared for the Office of Secretary of Defense, reaffirm conclusions from a 2008 Cochrane review that showed the herb is better than placebo and equal in efficacy to antidepressant therapy while having a better safety profile.1,2 Clinicians need to proceed with caution, though, because the evidence remains heterogeneous and little is known about the value of the herbal supplement in severe depressive disorder.

The Cochrane review evaluated 29 double-blind randomized controlled trials (N = 5489) of SJW versus placebo or antidepressant therapy for depression and concluded that the extracts evaluated were superior to placebo and equal to standard antidepressants with fewer adverse effects.2 Heterogeneity was large, though, which affected the confidence of the findings. Also, more positive results were seen in studies originating in German-speaking countries, leading the study authors to question whether a bias was at play.

The current study-also a systemic review-included trials represented in the Cochrane review but added studies beyond randomized controlled trials in hopes of establishing a fuller picture of the comparative value of SJW. The research team searched PubMed, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO, CENTRAL, Embase, the Allied and Complementary Medicine Database, MANTIS, Web of Science, the WHO International Clinical Trials Registry Platform, and other sources through November 2014. They assessed risk of bias using the Cochrane Risk of Bias tool and United States Preventive Services Task Force criteria and assessed quality of evidence (QoE) using the Cochrane-recommended GRADE approach (Grading of Recommendations, Assessment, Development and Evaluation).

Of 594 potentially relevant citations, 35, inclusive of 6993 patients, met inclusion criteria. Findings were similar to those of the earlier Cochrane review. SJW was associated with more responders than placebo (relative risk [RR], 1.53). Although treatment effect sizes were highly variable, the average response rate, based on treatment effect size, was 56% versus 35%. The treatment effect of SJW and antidepressant agents was equivalent (RR, 1.01) as were remission rates (38% vs 33%, respectively), with SJW being associated with less potential for adverse effects (odds ratio, 0.67). However, these findings apply only to mild to moderate depression because data on SJW in severe depression are lacking.

Message to clinicians

The QoE of these findings was moderate because of the heterogeneity of the studies reviewed. That is, the evidence is thought to be fairly sound and stable but also open to subsequent change. Beyond the need for more standardized methods of evaluating SJW, particularly its use in severe depression, the authors recommended that future research focus on comparisons of SJW extracts and dosage and more rigorously address safety. Their message to clinicians is that the results of this review may not apply to all patients with MDD, especially because the impact of SJW on severe depression is unknown.


1. Apaydin EA, Maher AR, Shanman R, et al. A systematic review of St. John's wort for major depressive disorder. Syst Rev. 2016;5:148.
2. Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database Syst Rev. 2008;4:CD000448.

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