Research Question

  1. What are the efficacy and safety of St. John's wort, as an adjunctive or monotherapy, for depressive symptoms and quality of life in adults with major depressive disorder compared with placebo or active comparator?

RAND researchers conducted a systematic review that synthesized evidence from randomized controlled trials of St. Johns wort (SJW) — used adjunctively or as monotherapy — to provide estimates of its efficacy and safety in treating adults with major depressive disorder.

Outcomes of interest included changes in depressive symptomatology, quality of life, and adverse effects. Efficacy meta-analyses used the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Quality of evidence was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach.

In total, 35 studies met inclusion criteria. There is moderate evidence, due to unexplained heterogeneity between studies, that depression improvement based on the number of treatment responders and depression scale scores favors SJW over placebo, and results are comparable to antidepressants. The existing evidence is based on studies testing SJW as monotherapy; there is a lack of evidence for SJW given as adjunct therapy to standard antidepressant therapy. We found no systematic difference between SJW extracts, but head-to-head trials are missing; LI 160 (0.3% hypericin, 1–4% hyperforin) was the extract with the greatest number of studies. Only two trials assessed quality of life. SJW adverse events reported in included trials were comparable to placebo, and were fewer compared with antidepressant medication; however, adverse event assessments were limited, and thus we have limited confidence in this conclusion.

Key Findings

St. John's Wort for Mild and Moderate Depression Outperforms Placebo and Is Comparable to Antidepressants, but the Evidence Has Limitations

  • The review showed that SJW given as monotherapy for mild and moderate depression is superior to placebo in improving symptoms and not significantly different from antidepressant medication; however, there was evidence of substantial heterogeneity between studies.
  • There is low quality evidence of no statistically significant difference in the number of patients in remission compared with placebo and antidepressants.
  • Only two trials assessed quality of life.
  • SJW adverse events reported in included trials were comparable to placebo groups, and there were fewer compared with antidepressant medication; however, adverse event assessments were limited and inadequate for rare events.
  • We found no systematic difference between SJW extracts, but head-to-head trials are missing; LI 160 (0.3% hypericin, 1–4% hyperforin) was the extract with the greatest number of studies.

Recommendations

  • Our conclusions are mostly in line with other reviews in this area. SJW is an effective treatment for mild and moderate major depressive disorder, with fewer adverse effects than standard antidepressants.
  • Reports of rare adverse events cannot be dismissed based on the existing randomized controlled trial data; larger studies with systematic adverse event assessments are needed.
  • While potential risks of drug interactions hinder research of SJW as an adjunctive treatment, research studies on SJW concomitant to psychotherapy are also missing.
  • Future research on the effectiveness of SJW should include more head-to-head trials between specific extracts and dosage of SJW.
  • As quality of life is greatly affected by major depressive disorder, more studies should include this measure.

Table of Contents

  • Chapter One

    Introduction

  • Chapter Two

    Methods

  • Chapter Three

    Results

  • Chapter Four

    Discussion

  • Appendix A

    Search Strategy

  • Appendix B

    Depression Scale Standard Cut-Points

  • Appendix C

    Excluded Full-Text Articles

  • Appendix D

    Evidence Table of Included Studies

This research was sponsored by the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury and conducted within the Forces and Resources Policy Center of the RAND National Defense Research Institute, a federally funded research and development center sponsored by the Office of the Secretary of Defense, the Joint Staff, the Unified Combatant Commands, the Navy, the Marine Corps, the defense agencies, and the defense Intelligence Community.

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