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2. 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

3. 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:
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

4. 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:
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

5. 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.

6. 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:
Mischoulon D et al. (2008) A double-blind dose-finding pilot study of docosahexaenoic acid (DHA) for major depressive disorder. Eur Neuropsychopharm; 18:

7. 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.

8. Safety Cycling to mania in bipolar disorder Common side effects Mild
Stomach upset
Studies using high doses between 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:e

9. 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:e

10. 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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