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EPA in major depressive disorder

Eicosapentaenoic acid appears to be the key omega-3 fatty acid component associated with efficacy in major depressive disorder: a critique of Bloch and Hannestad and updated meta-analysis

Molecular Psychiatry volume 17, pages 1144–1149 (2012)Cite this article

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A recent meta-analysis by Bloch and Hannestad (B&H)1 examining the efficacy of omega-3 fatty acids (ω3-FA) in major depressive disorder (MDD) claims no significant overall benefit compared with placebo; standard mean difference (SMD) 0.11 (95% CI, –0.04, 0.26) with no specific influence of eicosapentaenoic acid (EPA) dose on meta-regression analysis. These findings contrast with those from other recent meta-analyses.2, 3, 4, 5 As potential reasons for this disparity, we question the validity of their results on the basis of inclusion/exclusion criteria, study subgroup selection, strategy for selecting outcome measures, SMD estimates and choice of effect modifiers. Finally, we present a reanalysis yielding different conclusions.

B&H's stated inclusion criteria were ‘randomized and placebo-controlled trials examining the efficacy of ω3 FAs in adults with MDD… [, trials] examining the efficacy of ω3 FAs in treating MDD in subjects with medical comorbidity (that is, cardiac disease and Parkinson's disease) or pregnancy… [and trials examining] the efficacy of omega-3 FAs to target depressive symptoms (as a primary outcome) in patients who may not have received a formal psychiatric diagnosis (that is, in a primary care setting)’. However, B&H's reported aims, results and conclusions appear to be somewhat misleading as they comment exclusively on MDD when, by virtue of the third inclusion criteria, their meta-analysis included the study by Rogers et al.6 examining individuals with mild-to-moderate depression without formal psychiatric diagnosis. It appears, therefore, that their meta-analysis did not exclusively examine MDD as implied, but a broader categorization that included subclinical depressive symptoms that would not fulfill diagnostic criteria for a major depressive episode (MDE) or MDD.

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References

  1. Bloch MH, Hannestad J . Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. Mol Psychiatry 2011; e-pub ahead of print 20 September 2011; doi:10.1038/mp.2011.100.

    Article  Google Scholar 

  2. Appleton KM, Rogers PJ, Ness AR . Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr 2010; 91: 757–770.

    Article  CAS  Google Scholar 

  3. Martins JG . EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr 2009; 28: 525–542.

    Article  CAS  Google Scholar 

  4. Ross BM, Seguin J, Sieswerda LE . Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid? Lipids Health Dis 2007; 6: 21.

    Article  Google Scholar 

  5. Sublette ME, Ellis SP, Geant AL, Mann JJ . Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry 2011; 72: 1577–1584.

    Article  CAS  Google Scholar 

  6. Rogers PJ, Appleton KM, Kessler D, Peters TJ, Gunnell D, Hayward RC et al. No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: a randomised controlled trial. Br J Nutr 2008; 99: 421–431.

    Article  CAS  Google Scholar 

  7. Bot M, Pouwer F, Assies J, Jansen EH, Diamant M, Snoek FJ et al. Eicosapentaenoic acid as an add-on to antidepressant medication for co-morbid major depression in patients with diabetes mellitus: a randomized, double-blind placebo-controlled study. J Affect Disord 2010; 126: 282–286.

    Article  CAS  Google Scholar 

  8. Rondanelli M, Giacosa A, Opizzi A, Pelucchi C, La Vecchia C, Montorfano G et al. Eicosapentaenoic acid as an add-on to antidepressant medication for co-morbid major depression in patients with diabetes mellitus: a randomized, double-blind placebo-controlled study. J Am Coll Nutr 2010; 29: 55–64.

    Article  CAS  Google Scholar 

  9. Jazayeri S, Tehrani-Doost M, Keshavarz SA, Hosseini M, Djazayery A, Amini H et al. Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Aust N Z J Psychiatry 2008; 42: 192–198.

    Article  Google Scholar 

  10. Carney RM, Freedland KE, Rubin EH, Rich MW, Steinmeyer BC, Harris WS . Omega-3 augmentation of sertraline in treatment of depression in patients with coronary heart disease: a randomized controlled trial. JAMA 2009; 302: 1651–1657.

    Article  CAS  Google Scholar 

  11. Lucas M, Asselin G, Merette C, Poulin MJ, Dodin S . Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Am J Clin Nutr 2009; 89: 641–651.

    Article  CAS  Google Scholar 

  12. Freeman MP, Davis M, Sinha P, Wisner KL, Hibbeln JR, Gelenberg AJ . Omega-3 fatty acids and supportive psychotherapy for perinatal depression: a randomized placebo-controlled study. J Affect Disord 2008; 110: 142–148.

    Article  CAS  Google Scholar 

  13. Rees AM, Austin MP, Parker GB . Omega-3 fatty acids as a treatment for perinatal depression: randomized double-blind placebo-controlled trial. Aust N Z J Psychiatry 2008; 42: 199–205.

    Article  Google Scholar 

  14. Su KP, Huang SY, Chiu TH, Huang KC, Huang CL, Chang HC et al. Omega-3 fatty acids for major depressive disorder during pregnancy: results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2008; 69: 644–651.

    Article  CAS  Google Scholar 

  15. Grenyer BF, Crowe T, Meyer B, Owen AJ, Grigonis-Deane EM, Caputi P et al. Fish oil supplementation in the treatment of major depression: a randomised double-blind placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31: 1393–1396.

    Article  CAS  Google Scholar 

  16. Bax L, Yu LM, Ikeda N, Moons KG . A systematic comparison of software dedicated to meta-analysis of causal studies. BMC Med Res Methodol 2007; 7: 40.

    Article  Google Scholar 

  17. Su KP, Huang SY, Chiu CC, Shen WW . Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial. Eur Neuropsychopharmacol 2003; 13: 267–271.

    Article  CAS  Google Scholar 

  18. Appleton KM, Hayward RC, Gunnell D, Peters TJ, Rogers PJ, Kessler D et al. Effects of n-3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials. Am J Clin Nutr 2006; 84: 1308–1316.

    Article  CAS  Google Scholar 

  19. 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; 68: 1056–1061.

    Article  CAS  Google Scholar 

  20. Mischoulon D, Papakostas GI, Dording CM, Farabaugh AH, Sonawalla SB, Agoston AM et al. A double-blind, randomized controlled trial of ethyl-eicosapentaenoate for major depressive disorder. J Clin Psychiatry 2009; 70: 1636–1644.

    Article  CAS  Google Scholar 

  21. Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R . Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med 2008; 358: 252–260.

    Article  CAS  Google Scholar 

  22. Lespérance F, Frasure-Smith N, St-André E, Turecki G, Lespérance P, Wisniewski SR . The efficacy of omega-3 supplementation for major depression: a randomized controlled trial. J Clin Psychiatry 2011; 72: 1054–1062.

    Article  Google Scholar 

  23. Peet M, Horrobin DF . A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry 2002; 59: 913–919.

    Article  CAS  Google Scholar 

  24. Nemets B, Stahl Z, Belmaker RH . Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder. Am J Psychiatry 2002; 159: 477–479.

    Article  Google Scholar 

  25. Marangell LB, Martinez JM, Zboyan HA, Kertz B, Kim HF, Puryear LJ . A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Am J Psychiatry 2003; 160: 996–998.

    Article  Google Scholar 

  26. Silvers KM, Woolley CC, Hamilton FC, Watts PM, Watson RA . Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression. Prostaglandins Leukot Essent Fatty Acids 2005; 72: 211–218.

    Article  CAS  Google Scholar 

  27. da Silva TM, Munhoz RP, Alvarez C, Naliwaiko K, Kiss A, Andreatini R et al. Depression in Parkinson's disease: a double-blind, randomized, placebo-controlled pilot study of omega-3 fatty-acid supplementation. J Affect Disord 2008; 111: 351–359.

    Article  Google Scholar 

  28. Rush JA, First MB, Blacker D . Handbook of Psychiatric Measures. 2nd edn. American Psychiatric Publishing, Inc.: Washington, 2008.

    Google Scholar 

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Authors and Affiliations

  1. Academy of Nutritional Medicine, Cambridge, UK

    J G Martins

  2. Diakonhjemmet Hospital, Center for Psychopharmacology, Oslo, Norway

    H Bentsen

  3. Hammersmith Hospital and Imperial College London, London, UK

    B K Puri

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  1. J G Martins
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  2. H Bentsen
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  3. B K Puri
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Correspondence to J G Martins.

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Competing interests

JGM provides research consultancy to the Academy of Nutritional Medicine, which is a not-for-profit organization that amongst its various activities oversees a clinic providing nutritional interventions for a variety of disorders, including depression. JGM has not participated in this clinic and has never prescribed nutritional interventions to patients. BKP is the author of a patent for a product comprising botanical triterpenes, ethyl-eicosapentaenoate and gamma-linolenic acid and received partial salary support as principal investigator of a phase III trial of ethyl-eicosapentaenoate in Huntington's chorea (Huntington disease) from Amarin Neuroscience Ltd. (formerly known as Laxdale Ltd.) published as Puri BK et al., Neurology 2005;65:286–292. HB declares no conflict of interest.

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Martins, J., Bentsen, H. & Puri, B. Eicosapentaenoic acid appears to be the key omega-3 fatty acid component associated with efficacy in major depressive disorder: a critique of Bloch and Hannestad and updated meta-analysis. Mol Psychiatry 17, 1144–1149 (2012). https://doi.org/10.1038/mp.2012.25

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