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Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses
Open accessAbstract
OBJECTIVE: There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this area, to date no specialized systematic review (or meta-analysis) has been conducted. METHOD: 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, a random-effects model analyzed the standard mean difference between treatment and placebo in the change from baseline to endpoint, combining the effect size data. Funnel plot and heterogeneity analyses were also performed. RESULTS: Primarily positive results were found for replicated studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D, with positive isolated studies for creatine, folinic acid, and an amino acid combination. Mixed results were found for zinc, folic acid, vitamin C, and tryptophan, with nonsignificant results for inositol. No major adverse effects were noted in the studies (aside from minor digestive disturbance). A meta-analysis of adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3. Conversely, a meta-analysis of folic acid revealed a nonsignificant difference from placebo. Marked study heterogeneity was found in a Higgins test for both omega-3 and folic acid studies; funnel plots also revealed asymmetry (reflecting potential study bias). CONCLUSIONS: Current evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to reduce depressive symptoms.
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“Specific micronutrients such as omega-3 fatty acids and zinc may have an important effect on brain development and function independent of the gut microbiome [50].”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [50]
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Metadata
- Authors
- Sarris, J., Murphy, J., Mischoulon, D., Papakostas, G. I., Fava, M., Berk, M., & Ng, C. H.
- Affiliations
- Barwon Health (AU)
- From the ARCADIA Mental Health Research Group, Professorial Unit, Department of Psychiatry, The Melbourne Clinic, University of Melbourne, Melbourne, Australia; the Centre for Human Psychopharmacology, Swinburne University of Technology, Melbourne, Australia; the Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston; the IMPACT Strategic Research Centre, School of Medicine, Deakin University, Barwon Health, Geelong, Australia;...
- Venue
- American Journal of Psychiatry
- Published
- 2016-06-01
- Volume
- 173
- Issue
- 6
- Pages
- 575-587
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2345186616
- Cited by
- 436
- References
- 90
- Citations by year
- 2026: 13 · 2025: 42 · 2024: 36 · 2023: 23 · 2022: 42 · 2021: 34 · 2020: 95 · 2019: 55 · 2018: 33 · 2017: 46 · 2016: 15
- FWCI
- 5.72
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- cc-by
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- depression, nutraceuticals, adjunctive therapy, antidepressant augmentation, S-adenosylmethionine, methylfolate, omega-3 fatty acids, eicosapentaenoic acid, vitamin D, folic acid, creatine, zinc, tryptophan, myo-inositol, depressive symptoms
- MeSH terms
- Antidepressive Agents, Depression, Drug Therapy, Combination, Humans, Dietary Supplements
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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