Depression treated somewhat by Omega-3 (St. John's Wort better) – RAND org reviews 2015

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Omega-3 Fatty Acids for Major Depressive Disorder, A Systematic Review

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http://www.rand.org/pubs/research_reports/RR1079.html 2015
Sydne Newberry, Susanne Hempel, Marika Booth, Brett Ewing, Alicia Ruelaz Maher, Claire O'Hanlon, Jennifer Sloan, Christine Anne Vaughan, Whitney Dudley, Roberta M. Shanman, Melony E. Sorbero

What are the efficacy and safety of omega-3 fatty acid supplements, as an adjunctive or monotherapy, for depressive symptoms and quality of life in adults with major depressive disorder compared with placebo or active comparator?

Abstract
RAND researchers conducted a systematic review that synthesized evidence from randomized controlled trials of omega-3 fatty acids — used adjunctively or as monotherapy — to provide estimates of their 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 a modification of the Grades of Recommendation, Assessment, Development, and Evaluation (or GRADE) approach.

In total, 24 studies met inclusion criteria. All studies combined showed a small but significant effect of omega-3 fatty acids compared with placebo on depression scale scores and the proportion of treatment responders, but there was evidence of publication bias. Only two studies compared eicosapentaenoic acid (EPA) with docosahexaenoic acid (DHA) head to head. Pooling studies of EPA alone and those with a high EPA:DHA ratio revealed a significant effect on depression scale scores and on the proportion of treatment responders compared with placebo, but studies that administered DHA alone or a high DHA:EPA ratio showed no effect. Very few studies specified depression severity, and few studies assessed effects on quality of life. Omega-3 fatty acids were associated with an increased risk for mild gastrointestinal symptoms compared with placebo but not with other categories of mild adverse events or serious adverse events.

The omega-3 fatty acid EPA may have a small benefit in improving depression symptoms compared with placebo, with relatively minor gastrointestinal adverse events for adults with MDD, but the existing evidence base is weak.

Key Findings

Eicosapentaenoic Acid (EPA) for Mild and Moderate Depression Might Have a Small Benefit, but the Evidence Base Is Weak
The review showed that dietary supplements of omega-3 fatty acids may have a small benefit in improving depression symptoms compared with placebo; however, the quality of evidence for this conclusion is weak.
Subgroup analyses indicated higher efficacy of supplements that contain EPA or higher concentrations of EPA than DHA.
Benefits compared with placebo were primarily based on monotherapy studies.
Too few studies assessed effects of omega-3 fatty acids on remission and quality of life to draw conclusions.
Omega-3 fatty acids were associated with an increased risk for mild gastrointestinal symptoms but not with other categories of adverse events or serious adverse events.

Recommendations
Based on our assessment of the limitations of the existing literature and the relatively low risks involved, we believe two large trials are warranted. One trial should employ a 2x2 factorial design to assess the effects of mono- and adjunctive therapy in patients who have already responded to antidepressant therapy. A second trial should assess the effects of EPA monotherapy in individuals who may not be able to take antidepressants, including community-dwelling elderly, pregnant/postpartum women, and those with end-stage renal disease.
Research on differential effects of omega-3 fatty acids for individuals of different depression severity are needed, particularly their use in severe depression.
Assessment is also needed to identify those most likely to respond, presumably via a simple rapid biomarker test.
Table of Contents
Introduction
Methods
Results
Discussion and Conclusions
Appendix A – Search Strategy
Appendix B – Evidence Table of Included Studies
Appendix C – Excluded Full-Text Articles
Appendix D – Depression Scale Standard Cut-Points
Appendix E – Funnel Plots for Comparisons with Publication Bias

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St. John's Wort for Major Depressive Disorder – A Systematic Review

Alicia Ruelaz Maher, Susanne Hempel, Eric Apaydin, Roberta M. Shanman, Marika Booth, Jeremy N. V. Miles, Melony E. Sorbero
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Research Questions
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?

Abstract
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.