Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses.
Level 1 - systematic review of randomized trials
Systematic review and meta-analyses of clinical trials
PubMed 27113121 · doi:10.1176/appi.ajp.2016.15091228
What was done
A systematic search of PubMed, CINAHL, Cochrane Library, and Web of Science was conducted up to December 2015 for clinical trials using adjunctive nutrients for depression. Where sufficient data were available, random-effects meta-analyses assessed the standardized mean difference between active treatment and placebo from baseline to endpoint. Funnel plots and heterogeneity analyses were performed.
What was found
Replicated positive results were identified for S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D, with isolated positive studies for creatine, folinic acid, and an amino acid combination. Mixed results were found for zinc, folic acid, vitamin C, and tryptophan, and nonsignificant results for inositol. Meta-analysis of adjunctive omega-3 versus placebo showed a significant moderate-to-strong effect in favor of omega-3, whereas folic acid was nonsignificantly different from placebo. The abstract provides no exact numerical values, confidence intervals, or sample sizes. Marked study heterogeneity and funnel plot asymmetry were observed for both omega-3 and folic acid analyses. Adverse events were limited to minor digestive disturbance.
Why it matters
This review synthesizes clinical trial evidence on nutraceutical augmentation alongside antidepressants, identifying specific compounds like omega-3 and methylfolate that may improve antidepressant response.
Limits
The abstract does not report the total sample size, number of included studies, or specific quantitative effect sizes and confidence intervals. Significant heterogeneity and funnel plot asymmetry suggest potential publication bias and variability across included trials.
Cited by
- supports All published clinical studies evaluating creatine for depression have administered it as an adjunct to antidepressant therapy rather than as a monotherapy.