EXPLORING THE POTENTIAL ROLE OF OMEGA-3 FATTY ACIDS IN DEPRESSION
DOI:
https://doi.org/10.31435/ijitss.1(49).2026.5174Keywords:
Omega-3 Fatty Acids, Depression, Eicosapentaenoic Acid, Docosahexaenoic Acid, Major Depressive Disorder, Treatment-Resistant DepressionAbstract
Introduction: Depression represents a major public health challenge, affecting individuals worldwide and remaining a prevalent condition that significantly reduces quality of life. Despite the availability of various therapeutic options, including pharmacological interventions, these treatments are often insufficiently effective. Consequently, the search for safe and effective strategies to alleviate depressive symptoms remains a priority. Numerous studies have examined the potential role of omega-3 fatty acids in both the prevention and treatment of depression. In this context, the involvement of inflammatory processes and stress-related pathophysiological mechanisms appears to be particularly relevant. Therefore, research continues to investigate the potential relationship between omega-3 fatty acid supplementation and clinical improvement in patients with depression.
Aim of Study: The purpose of this review is to explore potential novel therapeutic strategies that may benefit patients with depression.
Material and methods: This narrative review synthesizes contemporary evidence regarding the role of omega-3 fatty acids in the prevention and treatment of depressive disorders. A targeted literature search was conducted using PubMed and Google Scholar. The search was focused primarily on studies published within the five-ten years. Search terms included combinations of “omega-3 fatty acids,” “eicosapentaenoic acid,” “docosahexaenoic acid,” “major depressive disorder,” “treatment-resistant depression". Randomized controlled trials, clinical trials, meta-analyses, systematic reviews, and high-quality narrative reviews were prioritized. Consistent with the narrative nature of this review, no formal systematic screening protocol, risk-of-bias assessment, or quantitative synthesis was performed.
Results and Conclusions: After examining the effects of omega-3 fatty acids in patients across different age groups, both as monotherapy and in combination with other agents, including postpartum women, studies have not produced conclusive evidence directly supporting their beneficial impact on depression.
References
Hellmann-Regen, J., et al. (2022). Effect of minocycline on depressive symptoms in patients with treatment-resistant depression: A randomized clinical trial. JAMA Network Open, 5(9), e2230367.
James, S. L., et al. (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017. The Lancet, 392(10159), 1789–1858.
Vyas, C. M., et al. (2023). Effects of vitamin D3 and marine omega-3 fatty acids supplementation on indicated and selective prevention of depression in older adults: Results from the Clinical Center sub-cohort of the VITamin D and OmegA-3 TriaL (VITAL). The Journal of Clinical Psychiatry, 84(4), 47683.
Okereke, O. I., et al. (2020). Effect of long-term vitamin D3 supplementation vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores: A randomized clinical trial. JAMA, 324(5), 471–480.
Schneider, E., et al. (2023). Effect of short-term, high-dose probiotic supplementation on cognition, related brain functions and BDNF in patients with depression: A secondary analysis of a randomized controlled trial. Journal of Psychiatry and Neuroscience, 48(1), E23–E33.
Nikolova, V. L., et al. (2023). Acceptability, tolerability, and estimates of putative treatment effects of probiotics as adjunctive treatment in patients with depression: A randomized clinical trial. JAMA Psychiatry, 80(8), 842–847.
Cattaneo, A., et al. (2020). Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study. Translational Psychiatry, 10(1), 232.
Chamberlain, S. R., et al. (2019). Treatment-resistant depression and peripheral C-reactive protein. The British Journal of Psychiatry, 214(1), 11–19.
Liu, J. J., et al. (2020). Peripheral cytokine levels and response to antidepressant treatment in depression: A systematic review and meta-analysis. Molecular Psychiatry, 25(2), 339–350.
Bekhbat, M., et al. (2022). Functional connectivity in reward circuitry and symptoms of anhedonia as therapeutic targets in depression with high inflammation: Evidence from a dopamine challenge study. Molecular Psychiatry, 27(10), 4113–4121.
Andersen, B. L., et al. (2023). Depression in association with neutrophil-to-lymphocyte, platelet-to-lymphocyte, and advanced lung cancer inflammation index biomarkers predicting lung cancer survival. PLoS One, 18(2), e0282206.
Valkanova, V., Ebmeier, K. P., & Allan, C. L. (2013). CRP, IL-6 and depression: A systematic review and meta-analysis of longitudinal studies. Journal of Affective Disorders, 150(3), 736–744.
Khandaker, G. M., et al. (2014). Association of serum interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life: A population-based longitudinal study. JAMA Psychiatry, 71(10), 1121–1128.
Benros, M. E., et al. (2013). Autoimmune diseases and severe infections as risk factors for mood disorders: A nationwide study. JAMA Psychiatry, 70(8).
Köhler, O., et al. (2014). Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: A systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry, 71(12), 1381–1391.
Müller, N., et al. (2006). The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: Results of a double-blind, randomized, placebo-controlled, add-on pilot study to reboxetine. Molecular Psychiatry, 11(7), 680–684.
Abbasi, S.-H., et al. (2012). Effect of celecoxib add-on treatment on symptoms and serum IL-6 concentrations in patients with major depressive disorder: Randomized double-blind placebo-controlled study. Journal of Affective Disorders, 141(2–3), 308–314.
Gougol, A., et al. (2015). Simvastatin as an adjuvant therapy to fluoxetine in patients with moderate to severe major depression: A double-blind placebo-controlled trial. Journal of Psychopharmacology, 29(5), 575–581.
Sepanjnia, K., et al. (2012). Pioglitazone adjunctive therapy for moderate-to-severe major depressive disorder: Randomized double-blind placebo-controlled trial. Neuropsychopharmacology, 37(9), 2093–2100.
Miyaoka, T., et al. (2012). Minocycline as adjunctive therapy for patients with unipolar psychotic depression: An open-label study. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 37(2), 222–226.
Abolfazli, R., et al. (2011). Double-blind randomized parallel-group clinical trial of efficacy of the combination fluoxetine plus modafinil versus fluoxetine plus placebo in the treatment of major depression. Depression and Anxiety, 28(4), 297–302.
DeBattista, C., et al. (2000). Acute antidepressant effects of intravenous hydrocortisone and CRH in depressed patients: A double-blind, placebo-controlled study. American Journal of Psychiatry, 157(8), 1334–1337.
Bloch, M. H., & Hannestad, J. (2012). Omega-3 fatty acids for the treatment of depression: Systematic review and meta-analysis. Molecular Psychiatry, 17(12), 1272–1282.
Krupa, K. N., Fritz, K., & Parmar, M. (2024). Omega-3 fatty acids. In StatPearls. StatPearls Publishing.
Bethesda, M. (2006). Drugs and lactation database (LactMed). National Library of Medicine.
Calder, P. C., et al. (2025). An overview of national and international long chain omega-3 polyunsaturated fatty acid intake recommendations for healthy populations. Nutrition Research Reviews, 1–33.
Zhang, Y., et al. (2024). Higher ratio of plasma omega-6/omega-3 fatty acids is associated with greater risk of all-cause, cancer, and cardiovascular mortality: A population-based cohort study in UK Biobank. eLife, 12, RP90132.
Lin, H., et al. (2025). Association of omega-3, omega-6 fatty acids intakes and omega-6:omega-3 ratio with the prevalence of suicidal ideation: Mediating role of C-reactive protein. Lipids in Health and Disease, 24(1), 178.
Jang, W., Kim, Y., & Kim, H. (2025). Association between the dietary omega-6 to omega-3 fatty acid ratio and age-related macular degeneration in Korean adults. Nutrition Journal, 24(1), 29.
Shakiba, E., et al. (2024). The relationship of dietary omega-3 fatty acid and omega-6 to omega-3 ratio intake and likelihood of type 2 diabetes in a cross-sectional study. BMC Endocrine Disorders, 24(1), 259.
Borsini, A., et al. (2021). Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: Relevance for major depression and for human hippocampal neurogenesis. Molecular Psychiatry, 26(11), 6773–6788.
Madison, A. A., et al. (2021). Omega-3 supplementation and stress reactivity of cellular aging biomarkers: An ancillary substudy of a randomized, controlled trial in midlife adults. Molecular Psychiatry, 26(7), 3034–3042.
Madison, A. A., et al. (2023). Omega-3 fatty acids reduce depressive symptoms only among the socially stressed: A corollary of the social signal transduction theory of depression. Health Psychology, 42(7), 448.
Bidzan-Wiącek, M., et al. (2024). No effects of omega-3 supplementation on kynurenine pathway, inflammation, depressive symptoms, and stress response in males: A placebo-controlled trial. Nutrients, 16(21), 3744.
Wang, J., et al. (2025). Effects of omega-3 PUFAs on lipid profiles and antioxidant response in depressed adolescents: A metabolomic and lipidomic study. Redox Biology, 82, 103617.
Berger, G., et al. (2026). ω-3 fatty acids in pediatric major depressive disorder: A randomized clinical trial. JAMA Network Open, 9(1), e2548703.
Chang, Y.-Y., et al. (2024). Omega-3 fatty acids for depression in the elderly and patients with dementia: A systematic review and meta-analysis. Healthcare, 12(5).
Gabbay, V., et al. (2018). A double-blind placebo-controlled trial of omega-3 fatty acids as a monotherapy for adolescent depression. The Journal of Clinical Psychiatry, 79(4), 17m11596.
Wu, S.-K., et al. (2024). The efficacy of omega-3 fatty acids as the monotherapy for depression: A randomized, double-blind, placebo-controlled pilot study. Nutrients, 16(21), 3688.
Qurashi, I., et al. (2024). A randomised double-blind placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at risk mental states: The NAYAB study. Brain, Behavior, and Immunity, 115, 609–616.
Okereke, O. I., et al. (2021). Effect of long-term supplementation with marine omega-3 fatty acids vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores: A randomized clinical trial. JAMA, 326(23), 2385–2394.
Thesing, C. S., et al. (2020). Supplementation-induced increase in circulating omega-3 serum levels is not associated with a reduction in depressive symptoms: Results from the MooDFOOD depression prevention trial. Depression and Anxiety, 37(11), 1079–1088.
Harauma, A., et al. (2023). Effects of varied omega-3 fatty acid supplementation on postpartum mental health and the association between prenatal erythrocyte omega-3 fatty acid levels and postpartum mental health. Nutrients, 15(20), 4388.
Freeman, M. P., et al. (2008). Omega-3 fatty acids and supportive psychotherapy for perinatal depression: A randomized placebo-controlled study. Journal of Affective Disorders, 110(1–2), 142–148.
Vaz, J. dos S., et al. (2017). Omega-3 supplementation from pregnancy to postpartum to prevent depressive symptoms: A randomized placebo-controlled trial. BMC Pregnancy and Childbirth, 17(1), 180.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Natalia Pawelec, Weronika Mazur, Edyta Hańczyk, Dawid Piecuch, Szymon Kopciał, Karolina Kornatowska, Anna Drużdżel
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
How to Cite
