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Omega-3 Fatty Acids: DHA and EPA David Mischoulon, MD, PhD Director, Depression Clinical and Research Program Massachusetts General Hospital Professor of Psychiatry Harvard Medical School

Omega-3 Fatty Acids DHA Docosahexaenoic acid 22 carbons EPA Eicosapentaenoic acid 20 carbons Freeman MP et al. (2006). Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry;67:1954-1967   Stoll AL. (2008): Omega-3 Fatty Acids In Mood Disorders: A Review of Neurobiological and Clinical Actions. Natural Medications in Psychiatric Disorders. Philadelphia: Lippincott Williams & Wilkins. Pp.39-67

Long chain polyunsaturated omega-3 fatty acids Found in fish oil and marine sources e.g. algae Mechanism: Stabilization of the neuronal membrane Anti-inflammatory effects Freeman MP et al. (2006) Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. J Clin Psychiatry;67:1954-1967   Stoll AL. (2008): Omega-3 Fatty Acids In Mood Disorders: A Review of Neurobiological and Clinical Actions. Natural Medications in Psychiatric Disorders. Philadelphia: Lippincott Williams & Wilkins. Pp.39-67.

Adjunctive to standard antidepressant > 30 RCTs Adjunctive to standard antidepressant Or combination of EPA plus DHA Used EPA only Effective dose: 1- 2 g / day Grosso G et al. (2014). Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS One; 9:e96905.

Omega-3 Fatty Acids Meta-analysis: Sublette et al DHA alone as an antidepressant Limited evidence Most effective omega-3 preparation: A few studies: mixed results Anti-suicide effects: needs to be confirmed ~ 60% EPA relative to DHA Sublette ME et al. (2011) Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry; 72:1577-1584. Mischoulon D et al. (2008) A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder. Eur Neuropsychopharm; 18:639-645.

Efficacy Bipolar disorder Postpartum depression May be best for the depressive phase Results preliminary More studies are required Freeman, M. P. et al. (2006). Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression. Acta Psychiatrica Scandinavica, 113(1), 31–35.   Marangell, L. B. et al. (2004) Omega-3 fatty acids for the prevention of postpartum depression: negative data from a preliminary, open-label pilot study. Depression and Anxiety, 19(1), 20–23. Stoll, A. L. et al. (1999). Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Archives of General Psychiatry, 56(5), 407–412. Keck, P. E. et al. (2006). Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biological Psychiatry, 60(9), 1020–1022. Sarris J et al. (2012) Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression. J Clin Psychiatry;73:81-86.

Safety Cycling to mania in bipolar disorder Common side effects Mild Stomach upset Studies using high doses between 6 -10 g / day Fishy taste Caution is advised in bipolar patients Bleeding Doses greater than 3 g / day Recent evidence: safe Stoll AL. (2008): Omega-3 Fatty Acids In Mood Disorders: A Review of Neurobiological and Clinical Actions. In: Mischoulon D, Rosenbaum J, editors. Natural Medications in Psychiatric Disorders. Philadelphia: Lippincott Williams & Wilkins. Pp.39-67   Mazza M et al. (2015) The complex interplay of Depression, Inflammation and Omega-3: state of the art and progresses in research. Clin Ter;166:e242-247

Pregnancy depletes omega-3s in the mother Important for Fetal brain development Postpartum depression Allergy prevention Unknown safe upper limit of dosing Safe Potentially beneficial Caution in pregnant women Stoll AL. (2008): Omega-3 Fatty Acids In Mood Disorders: A Review of Neurobiological and Clinical Actions. In: Mischoulon D, Rosenbaum J, editors. Natural Medications in Psychiatric Disorders. Philadelphia: Lippincott Williams & Wilkins. Pp.39-67   Mazza M et al. (2015) The complex interplay of Depression, Inflammation and Omega-3: state of the art and progresses in research. Clin Ter;166:e242-247

Key Points The omega-3 fatty acids may have broad applications in psychiatric disorders. EPA and DHA are thought to be the most psychotropically active of the omega-3 family of fatty acids. Depression appears to be the most supported indication for the omega-3s.

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