Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression.
Trials evaluating efficacy of omega-3 highly unsaturated fatty acids (HUFAs) in major depressive disorder report discrepant findings.



To establish the reasons underlying inconsistent findings among randomised controlled trials (RCTs) of omega-3 HUFAs for depression and to assess implications for further trials.



A systematic bibliographic search of double-blind RCTs was conducted between January 1980 and July 2014 and an exploratory hypothesis-testing meta-analysis performed in 35 RCTs including 6665 participants receiving omega-3 HUFAs and 4373 participants receiving placebo.



Among participants with diagnosed depression, eicosapentaenoic acid (EPA)-predominant formulations (>50% EPA) demonstrated clinical benefits compared with placebo (Hedge's G = 0.61, P<0.001) whereas docosahexaenoic acid (DHA)-predominant formulations (>50% DHA) did not. EPA failed to prevent depressive symptoms among populations not diagnosed for depression.



Further RCTs should be conducted on study populations with diagnosed or clinically significant depression of adequate duration using EPA-predominant omega-3 HUFA formulations.
Brian Hallahan, MRCPsych, MD, Department of Psychiatry, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland; Timothy Ryan, BA, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Joseph R. Hibbeln, MD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; Ivan T. Murray, MRCPsych, Department of Psychiatry, University Hospital Galway, Galway, Ireland; Shauna Glynn, MRCPsych, Child and Adolescent Mental Health Services, Castlebar, Mayo, Ireland; Christopher E. Ramsden, MD, John Paul SanGiovanni, ScD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; John M. Davis, MD, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA brian.hallahan@nuigalway.ie.
Brian
B
Hallahan
Brian Hallahan, MRCPsych, MD, Department of Psychiatry, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland; Timothy Ryan, BA, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Joseph R. Hibbeln, MD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; Ivan T. Murray, MRCPsych, Department of Psychiatry, University Hospital Galway, Galway, Ireland; Shauna Glynn, MRCPsych, Child and Adolescent Mental Health Services, Castlebar, Mayo, Ireland; Christopher E. Ramsden, MD, John Paul SanGiovanni, ScD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; John M. Davis, MD, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
Timothy
T
Ryan
Brian Hallahan, MRCPsych, MD, Department of Psychiatry, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland; Timothy Ryan, BA, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Joseph R. Hibbeln, MD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; Ivan T. Murray, MRCPsych, Department of Psychiatry, University Hospital Galway, Galway, Ireland; Shauna Glynn, MRCPsych, Child and Adolescent Mental Health Services, Castlebar, Mayo, Ireland; Christopher E. Ramsden, MD, John Paul SanGiovanni, ScD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; John M. Davis, MD, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
Joseph R
JR
Hibbeln
Brian Hallahan, MRCPsych, MD, Department of Psychiatry, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland; Timothy Ryan, BA, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Joseph R. Hibbeln, MD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; Ivan T. Murray, MRCPsych, Department of Psychiatry, University Hospital Galway, Galway, Ireland; Shauna Glynn, MRCPsych, Child and Adolescent Mental Health Services, Castlebar, Mayo, Ireland; Christopher E. Ramsden, MD, John Paul SanGiovanni, ScD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; John M. Davis, MD, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
Ivan T
IT
Murray
Brian Hallahan, MRCPsych, MD, Department of Psychiatry, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland; Timothy Ryan, BA, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Joseph R. Hibbeln, MD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; Ivan T. Murray, MRCPsych, Department of Psychiatry, University Hospital Galway, Galway, Ireland; Shauna Glynn, MRCPsych, Child and Adolescent Mental Health Services, Castlebar, Mayo, Ireland; Christopher E. Ramsden, MD, John Paul SanGiovanni, ScD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; John M. Davis, MD, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
Shauna
S
Glynn
Brian Hallahan, MRCPsych, MD, Department of Psychiatry, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland; Timothy Ryan, BA, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Joseph R. Hibbeln, MD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; Ivan T. Murray, MRCPsych, Department of Psychiatry, University Hospital Galway, Galway, Ireland; Shauna Glynn, MRCPsych, Child and Adolescent Mental Health Services, Castlebar, Mayo, Ireland; Christopher E. Ramsden, MD, John Paul SanGiovanni, ScD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; John M. Davis, MD, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
Christopher E
CE
Ramsden
Brian Hallahan, MRCPsych, MD, Department of Psychiatry, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland; Timothy Ryan, BA, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Joseph R. Hibbeln, MD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; Ivan T. Murray, MRCPsych, Department of Psychiatry, University Hospital Galway, Galway, Ireland; Shauna Glynn, MRCPsych, Child and Adolescent Mental Health Services, Castlebar, Mayo, Ireland; Christopher E. Ramsden, MD, John Paul SanGiovanni, ScD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; John M. Davis, MD, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
John Paul
JP
SanGiovanni
Brian Hallahan, MRCPsych, MD, Department of Psychiatry, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland; Timothy Ryan, BA, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA; Joseph R. Hibbeln, MD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; Ivan T. Murray, MRCPsych, Department of Psychiatry, University Hospital Galway, Galway, Ireland; Shauna Glynn, MRCPsych, Child and Adolescent Mental Health Services, Castlebar, Mayo, Ireland; Christopher E. Ramsden, MD, John Paul SanGiovanni, ScD, Section on Nutritional Neurosciences, Laboratory of Membrane Biochemistry & Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA; John M. Davis, MD, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
John M
JM
Davis
D003865:Major Depressive Disorder / Q000178:diet therapy*; D004281:Docosahexaenoic Acids / Q000627:therapeutic use; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D006801:Humans
D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid