Impact of Omega-3 on the Treatment of Depressive Disorder: A Literature Review
DOI:
https://doi.org/10.61661/congresso.cbmev.7.2024.112Keywords:
Omega-3 Fatty Acids, Major Depressive Disorder, EfficacyAbstract
Introduction: Major Depressive Disorder (MDD) is one of the leading causes of global disability. However, current treatment options for depression remain limited by efficacy, cost, availability, side effects, and patient acceptability. In this context, the value of omega-3 polyunsaturated fatty acids (PUFAs) is still overlooked, despite the widely supported benefits of their use in various studies. Objectives: To examine empirical evidence of the association between omega-3 fatty acids and depression, discuss possible mechanisms of action, and explore the clinical implications of such findings. Methodology: A narrative review was conducted, with a survey of 28 articles published between 2019 and 2024. Results: Studies demonstrated the efficacy of omega-3 use as an adjunctive therapy to reduce the severity of depression. However, treatment response may vary depending on the presence of comorbidities in depressed individuals, highlighting the need for personalized treatment strategies. Conclusion: Further research is needed to improve the application of omega-3 PUFA supplementation and to refine personalized medicine strategies, thereby increasing the effectiveness of interventions for this heterogeneous population of patients.
References
Sijbesma, F.; Sheeran, J. Micronutrients, Macro Impact: The Story of Vitamins and a Hungry World. Waldkirch: Sight and Life. 2011. Available online: http://www.sightandlife.org/fileadmin/data/Books/ Micronutrients_Macro_Impact.pdf (accessed on 1 June 2017)
World mental health report: transforming mental health for all. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO. ISBN 978-92-4-004933-8 (electronic version). Link 9789240049338-eng.pdf (sbponline.org.br).
Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002 Oct;56(8):365-79. doi: 10.1016/s0753-3322(02)00253-6. PMID: 12442909. DOI: https://doi.org/10.1016/S0753-3322(02)00253-6
Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman G, Murray CJ, Vos T, Whiteford HA. Burden of depressive disorders by country, sex, age, and year: findings from the global burden of disease study 2010. PLoS Med. 2013 Nov;10(11):e1001547. doi: 10.1371/journal.pmed.1001547. Epub 2013 Nov 5. PMID: 24223526; PMCID: PMC3818162. DOI: https://doi.org/10.1371/journal.pmed.1001547
American Psychiatric Association. Manual Diagnóstico e Estatístico de Transtornos Mentais. 5a ed. Texto revisado.DSM-5-TR. Porto Alegre: Artmed, 2023.
Jerome Sarris, Arun Ravindran, Lakshmi N. Yatham, Wolfgang Marx, Julia J. Rucklidge, Roger S. McIntyre, Shahin Akhondzadeh, Francesco Benedetti, Constanza Caneo, Holger Cramer, Lachlan Cribb, Michael de Manincor, Olivia Dean, Andrea Camaz Deslandes, Marlene P. Freeman, Bangalore Gangadhar, Brian H. Harvey, Siegfried Kasper, James Lake, Adrian Lopresti, Lin Lu, Najwa-Joelle Metri, David Mischoulon, Chee H. Ng, Daisuke Nishi, Roja Rahimi, Soraya Seedat, Justin Sinclair, Kuan-Pin Su, Zhang-Jin Zhang & Michael Berk (2022) Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce, The World Journal of Biological Psychiatry, 23:6, 424-455, DOI: 10.1080/15622975.2021.2013041 DOI: https://doi.org/10.1080/15622975.2021.2013041
Ta-Wei Guu, David Mischoulon, Jerome Sarris, Joseph Hibbeln, Robert K McNamara, Kei Hamazaki, Marlene P Freeman, Michael Maes, Yutaka J Matsuoka, R H Belmaker, Felice Jacka, Carmine Pariante, Michael Berk, Wolfgang Marx , Kuan-Pin Su International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder. Psychother Psychosom 2019;88:263–273 DOI: 10.1159/000502652 DOI: https://doi.org/10.1159/000502652
Grosso G, Micek A, Marventano S, Castellano S, Mistretta A, Pajak A, Galvano F. Dietary n-3 PUFA, fish consumption and depression: A systematic review and meta-analysis of observational studies. J Affect Disord. 2016 Nov 15;205:269-281. doi: 10.1016/j.jad.2016.08.011. Epub 2016 Aug 16. PMID: 27544316. DOI: https://doi.org/10.1016/j.jad.2016.08.011
Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry. 2007 Jul;68(7):1056-61. doi: 10.4088/jcp.v68n0712. PMID: 17685742. DOI: https://doi.org/10.4088/JCP.v68n0712
Cussotto S, Delgado I, Oriolo G, Kemper J, Begarie D, Dexpert S, Sauvant J, Leboyer M, Aouizerate B, Martin-Santos R, Schaefer M, Capuron L. Low omega-3 polyunsaturated fatty acids predict reduced response to standard antidepressants in patients with major depressive disorder. Depress Anxiety. 2022 May;39(5):407-418. doi: 10.1002/da.23257. Epub 2022 Mar 31. PMID: 35357051. DOI: https://doi.org/10.1002/da.23257
Van Verseveld M, Mocking RJT, Scheepens D, Ten Doesschate F, Westra M, Schoevers RA, Schene AH, van Wingen GA, van Waarde JA, Ruhé HG. Polyunsaturated fatty acids changes during electroconvulsive therapy in major depressive disorder. J Psychiatr Res. 2023 Apr;160:232-239. doi: 10.1016/j.jpsychires.2023.02.028. Epub 2023 Feb 27. PMID: 36868104. DOI: https://doi.org/10.1016/j.jpsychires.2023.02.028
Yang R, Wang L, Jin K, Cao S, Wu C, Guo J, Chen J, Tang H, Tang M. Omega-3 Polyunsaturated Fatty Acids Supplementation Alleviate Anxiety Rather Than Depressive Symptoms Among First-Diagnosed, Drug-Naïve Major Depressive Disorder Patients: A Randomized Clinical Trial. Front Nutr. 2022 Jul 12;9:876152. doi: 10.3389/fnut.2022.876152. PMID: 35903448; PMCID: PMC9315396. DOI: https://doi.org/10.3389/fnut.2022.876152
Carnegie R, Borges MC, Jones HJ, Zheng J, Haycock P, Evans J, Martin RM. Omega-3 fatty acids and major depression: a Mendelian randomization study. Transl Psychiatry. 2024 May 29;14(1):222. doi: 10.1038/s41398-024-02932-w. PMID: 38811538; PMCID: PMC11136966. DOI: https://doi.org/10.1038/s41398-024-02932-w
Osuna E, Herter-Aeberli I, Probst S, Emery S, Albermann M, Baumgartner N, Strumberger M, Ricci C, Schmeck K, Walitza S, Hersberger M, Zimmermann MB, Häberling I, Berger G, Baumgartner J; Omega-3 study team. Associations of n-3 polyunsaturated fatty acid status and intake with paediatric major depressive disorder in Swiss adolescents: A case-control study. J Affect Disord. 2023 Oct 15;339:355-365. doi: 10.1016/j.jad.2023.07.046. Epub 2023 Jul 10. PMID: 37437731. DOI: https://doi.org/10.1016/j.jad.2023.07.046
Davyson E, Shen X, Gadd DA, Bernabeu E, Hillary RF, McCartney DL, Adams M, Marioni R, McIntosh AM. Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids. Biol Psychiatry. 2023 Oct 15;94(8):630-639. doi: 10.1016/j.biopsych.2023.01.027. Epub 2023 Feb 9. Erratum in: Biol Psychiatry. 2024 Jan 1;95(1):93. doi: 10.1016/j.biopsych.2023.10.001. PMID: 36764567; PMCID: PMC10804990. DOI: https://doi.org/10.1016/j.biopsych.2023.01.027
Borsini A, Nicolaou A, Camacho-Muñoz D, Kendall AC, Di Benedetto MG, Giacobbe J, Su KP, Pariante CM. 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. Mol Psychiatry. 2021 Nov;26(11):6773-6788. doi: 10.1038/s41380-021-01160-8. Epub 2021 Jun 16. PMID: 34131267; PMCID: PMC8760043. DOI: https://doi.org/10.1038/s41380-021-01160-8
Appleton KM, Voyias PD, Sallis HM, Dawson S, Ness AR, Churchill R, Perry R. Omega-3 fatty acids for depression in adults. Cochrane Database Syst Rev. 2021 Nov 24;11(11):CD004692. doi: 10.1002/14651858.CD004692.pub5. PMID: 34817851; PMCID: PMC8612309. DOI: https://doi.org/10.1002/14651858.CD004692.pub5
Wolters M, von der Haar A, Baalmann AK, Wellbrock M, Heise TL, Rach S. Effects of n-3 Polyunsaturated Fatty Acid Supplementation in the Prevention and Treatment of Depressive Disorders-A Systematic Review and Meta-Analysis. Nutrients. 2021 Mar 25;13(4):1070. doi: 10.3390/nu13041070. PMID: 33806078; PMCID: PMC8064470. DOI: https://doi.org/10.3390/nu13041070
Thesing CS, Lok A, Milaneschi Y, Assies J, Bockting CLH, Figueroa CA, Giltay EJ, Penninx BWJH, Ruhé HG, Schene AH, Bot M, Mocking RJT. Fatty acids and recurrence of major depressive disorder: combined analysis of two Dutch clinical cohorts. Acta Psychiatr Scand. 2020 Apr;141(4):362-373. doi: 10.1111/acps.13136. Epub 2019 Dec 26. PMID: 31785112; PMCID: PMC7216896. DOI: https://doi.org/10.1111/acps.13136
Chang JP, Chang SS, Yang HT, Chen HT, Chien YC, Yang B, Su H, Su KP. Omega-3 polyunsaturated fatty acids in cardiovascular diseases comorbid major depressive disorder - Results from a randomized controlled trial. Brain Behav Immun. 2020 Mar;85:14-20. doi: 10.1016/j.bbi.2019.03.012. Epub 2019 Mar 19. PMID: 30902738. DOI: https://doi.org/10.1016/j.bbi.2019.03.012
Carney RM, Freedland KE, Rubin EH, Rich MW, Steinmeyer BC, Harris WS. A Randomized Placebo-Controlled Trial of Omega-3 and Sertraline in Depressed Patients With or at Risk for Coronary Heart Disease. J Clin Psychiatry. 2019 Jun 4;80(4):19m12742. doi: 10.4088/JCP.19m12742. PMID: 31163106; PMCID: PMC6550340. DOI: https://doi.org/10.4088/JCP.19m12742
Guu TW, Mischoulon D, Sarris J, Hibbeln J, McNamara RK, Hamazaki K, Freeman MP, Maes M, Matsuoka YJ, Belmaker RH, Marx W, Pariante C, Berk M, Jacka F, Su KP. A multi-national, multi-disciplinary Delphi consensus study on using omega-3 polyunsaturated fatty acids (n-3 PUFAs) for the treatment of major depressive disorder. J Affect Disord. 2020 Mar 15;265:233-238. doi: 10.1016/j.jad.2020.01.050. Epub 2020 Jan 15. Erratum in: J Affect Disord. 2020 Sep 1;274:1226-1227. doi: 10.1016/j.jad.2020.06.007. PMID: 32090746. DOI: https://doi.org/10.1016/j.jad.2020.06.007
Suneson K, Söderberg Veibäck G, Lindahl J, Tjernberg J, Ståhl D, Ventorp S, Ängeby F, Lundblad K, Wolkowitz OM, Lindqvist D. Omega-3 fatty acids for inflamed depression - A match/mismatch study. Brain Behav Immun. 2024 May;118:192-201. doi: 10.1016/j.bbi.2024.02.029. Epub 2024 Mar 1. PMID: 38432599.
Lamon-Fava S, So J, Mischoulon D, Ziegler TR, Dunlop BW, Kinkead B, Schettler PJ, Nierenberg AA, Felger JC, Maddipati KR, Fava M, Rapaport MH. Dose- and time-dependent increase in circulating anti-inflammatory and pro-resolving lipid mediators following eicosapentaenoic acid supplementation in patients with major depressive disorder and chronic inflammation. Prostaglandins Leukot Essent Fatty Acids. 2021 Jan;164:102219. doi: 10.1016/j.plefa.2020.102219. Epub 2020 Dec 5. PMID: 33316626; PMCID: PMC7855824. DOI: https://doi.org/10.1016/j.plefa.2020.102219
Wu SK, Chen WJ, Chang JP, Guu TW, Hsin MC, Huang CK, Mischoulon D, Capuron L, Su KP. Personalized Medicine of Omega-3 Fatty Acids in Depression Treatment in Obese and Metabolically Dysregulated Patients. J Pers Med. 2023 Jun 15;13(6):1003. doi: 10.3390/jpm13061003. PMID: 37373992; PMCID: PMC10300918. DOI: https://doi.org/10.3390/jpm13061003
Bazinet RP, Metherel AH, Chen CT, Shaikh SR, Nadjar A, Joffre C, Layé S. Brain eicosapentaenoic acid metabolism as a lead for novel therapeutics in major depression. Brain Behav Immun. 2020 Mar;85:21-28. doi: 10.1016/j.bbi.2019.07.001. Epub 2019 Jul 3. PMID: 31278982. DOI: https://doi.org/10.1016/j.bbi.2019.07.001
Accinni T, Panfili M, Tarsitani L, Biondi M, Pasquini M, Maraone A. A Revision on the Effectiveness of Omega-3 Polyunsaturated Fatty Acids as Monotherapy in the Treatment of Major Depressive Disorder. Int J Clin Pract. 2022 Nov 16;2022:3801235. doi: 10.1155/2022/3801235. PMID: 36474548; PMCID: PMC9683950. DOI: https://doi.org/10.1155/2022/3801235
Liao Y, Xie B, Zhang H, He Q, Guo L, Subramanieapillai M, Fan B, Lu C, McIntyre RS. Efficacy of omega-3 PUFAs in depression: A meta-analysis. Transl Psychiatry. 2019 Aug 5;9(1):190. doi: 10.1038/s41398-019-0515-5. Erratum in: Transl Psychiatry. 2021 Sep 7;11(1):465. doi: 10.1038/s41398-021-01582-6. PMID: 31383846; PMCID: PMC6683166. DOI: https://doi.org/10.1038/s41398-021-01582-6
Luo XD, Feng JS, Yang Z, Huang QT, Lin JD, Yang B, Su KP, Pan JY. High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: a network meta-analysis. BMC Psychiatry. 2020 May 20;20(1):248. doi: 10.1186/s12888-020-02656-3. PMID: 32434488; PMCID: PMC7238659. DOI: https://doi.org/10.1186/s12888-020-02656-3
Mischoulon D, Dunlop BW, Kinkead B, Schettler PJ, Lamon-Fava S, Rakofsky JJ, Nierenberg AA, Clain AJ, Mletzko Crowe T, Wong A, Felger JC, Sangermano L, Ziegler TR, Cusin C, Fisher LB, Fava M, Rapaport MH. Omega-3 Fatty Acids for Major Depressive Disorder With High Inflammation: A Randomized Dose-Finding Clinical Trial. J Clin Psychiatry. 2022 Aug 22;83(5):21m14074. doi: 10.4088/JCP.21m14074. PMID: 36005883. DOI: https://doi.org/10.4088/JCP.21m14074
Tayama J, Ogawa S, Nakaya N, Sone T, Hamaguchi T, Takeoka A, Hamazaki K, Okamura H, Yajima J, Kobayashi M, Hayashida M, Shirabe S. Omega-3 polyunsaturated fatty acids and psychological intervention for workers with mild to moderate depression: A double-blind randomized controlled trial. J Affect Disord. 2019 Feb 15;245:364-370. doi: 10.1016/j.jad.2018.11.039. Epub 2018 Nov 6. PMID: 30423463. DOI: https://doi.org/10.1016/j.jad.2018.11.039
Trebatická J, Hradečná Z, Surovcová A, Katrenčíková B, Gushina I, Waczulíková I, Sušienková K, Garaiova I, Šuba J, Ďuračková Z. Omega-3 fatty-acids modulate symptoms of depressive disorder, serum levels of omega-3 fatty acids and omega-6/omega-3 ratio in children. A randomized, double-blind and controlled trial. Psychiatry Res. 2020 May;287:112911. doi: 10.1016/j.psychres.2020.112911. Epub 2020 Mar 7. PMID: 32179212. DOI: https://doi.org/10.1016/j.psychres.2020.112911
Suneson K, Söderberg Veibäck G, Lindahl J, Tjernberg J, Ståhl D, Ventorp S, Ängeby F, Lundblad K, Wolkowitz OM, Lindqvist D. Omega-3 fatty acids for inflamed depression - A match/mismatch study. Brain Behav Immun. 2024 May;118:192-201. doi: 10.1016/j.bbi.2024.02.029. Epub 2024 Mar 1. PMID: 38432599. DOI: https://doi.org/10.1016/j.bbi.2024.02.029
Thesing CS, Milaneschi Y, Bot M, Brouwer IA, Owens M, Hegerl U, Gili M, Roca M, Kohls E, Watkins E, Visser M, Penninx BWJH. 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. Depress Anxiety. 2020 Nov;37(11):1079-1088. doi: 10.1002/da.23092. Epub 2020 Aug 26. PMID: 32845021; PMCID: PMC7693241. DOI: https://doi.org/10.1002/da.23092
Okereke OI, Vyas CM, Mischoulon D, Chang G, Cook NR, Weinberg A, Bubes V, Copeland T, Friedenberg G, Lee IM, Buring JE, Reynolds CF 3rd, Manson JE. 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. 2021 Dec 21;326(23):2385-2394. doi: 10.1001/jama.2021.21187. PMID: 34932079; PMCID: PMC8693224. DOI: https://doi.org/10.1001/jama.2021.21187
Vyas CM, Mischoulon D, Chang G, Cook NR, Weinberg A, Copeland T, Kang JH, Bubes V, Friedenberg G, LeBoff MS, Lee IM, Buring JE, Manson JE, Reynolds CF, Okereke OI. 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). J Clin Psychiatry. 2023 Jun 26;84(4):22m14629. doi: 10.4088/JCP.22m14629. PMID: 37378490; PMCID: PMC10328718. DOI: https://doi.org/10.4088/JCP.22m14629
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