Omega-3 Fatty Acids: Evidence Basis for Treatment and Future Research in Psychiatry

Marlene P. Freeman, M.D.; Joseph R. Hibbeln, M.D.; Katherine L. Wisner, M.D., M.S.; John M. Davis, M.D.; David Mischoulon, M.D., Ph.D.; Malcolm Peet, M.B., F.R.C.Psych.; Paul E. Keck, Jr., M.D.; Lauren B. Marangell, M.D.; Alexandra J. Richardson, Ph.D.; James Lake, M.D.; and Andrew L. Stoll, M.D.

Objective: To determine if the available data support the use of omega-3 essential fatty acids (EFA) for clinical use in the prevention and/or treatment of psychiatric disorders.

Participants: The authors of this article were invited participants in the Omega-3 Fatty Acids Subcommittee, assembled by the Committee on Research on Psychiatric Treatments of the American Psychiatric Association (APA).

Evidence: Published literature and data presented at scientific meetings were reviewed. Specific disorders reviewed included major depressive disorder, bipolar disorder, schizophrenia, dementia, borderline personality disorder and impulsivity, and attention-deficit/hyperactivity disorder. Meta-analyses were conducted in major depressive and bipolar disorders and schizophrenia, as sufficient data were availableto conduct such analyses in these areas of interest.

Consensus Process: The subcommittee prepared the manuscript, which was reviewed and approved by the following APA committees: the Committee on Research on Psychiatric Treatments, the Council on Research, and the Joint Reference Committee.

Conclusions: The preponderance of epidemiologic and tissue compositional studies supports a protective effect of omega-3 EFA intake, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in mood disorders. Meta-analyses of randomized controlled trials demonstrate a statistically significant benefit in unipolar and bipolar depression (p=.02). The results were highly heterogeneous, indicating that it is important to examine the characteristics of each individual study to note the differences in design and execution. There is less evidence of benefit in schizophrenia. EPA and DHA appear to have negligible risks and some potential benefit in major depressive disorder and bipolar disorder, but results remain inconclusive in most areas of interest in psychiatry. Treatment recommendations and directions for future research are described. Health benefits of omega-3 EFA may be especially important in patients with psychiatric disorders, due to high prevalence rates of smoking and obesity and the metabolic side effects of some psychotropic medications.

(J Clin Psychiatry 2006;67:1954-1967)

Received April 7, 2006; accepted May 24, 2006. From the Women's Mental Health Program, Departments of Psychiatry, Obstetrics and Gynecology, and Nutritional Sciences, University of Arizona College of Medicine, Tucson (Dr. Freeman); the National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md. (Dr. Hibbeln); the Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pa. (Dr. Wisner); the Department of Psychiatry, University of Illinois at Chicago, and Maryland Psychiatric Research Center, Baltimore (Dr. Davis); Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Mass. (Dr. Mischoulon); School of Health and Related Research, University of Sheffield, Sheffield, England (Dr. Peet); the Psychopharmacology Research Program, the Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio (Dr. Keck); the Department of Psychiatry, Baylor College of Medicine, and the VISN 16 Mental Illness Research Education and Clinical Core, Department of Veterans Affairs, Houston, Tex. (Dr. Marangell); the Department of Physiology, Human Anatomy, and Genetics, Oxford University, Oxford, England (Dr. Richardson); the Department of Psychiatry and Center for Integrative Medicine, Stanford University, Palo Alto, Calif. (Dr. Lake); and the Department of Psychiatry, McLean Hospital, Harvard Medical School, Boston, Mass. (Dr. Stoll).

The American Psychiatric Association provided administrative support for this committee. Supported by grant 5K23MH066265 from the National Institute of Mental Health (Dr. Freeman), grant 5 K23 AT001129-05 from the National Center for Complementary and Alternative Medicine (Dr. Mischoulon), a National Alliance for Research on Schizophrenia and Depression Young Investigator Award (Dr. Mischoulon), and Food and Behaviour Research and the Dyslexia Research Trust (Dr. Richardson).

Financial disclosure is listed at the end of this article.

The authorship contribution of Dr. Hibbeln is not a position or opinion of the National Institute on Alcohol Abuse and Alcoholism.

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Complementary and Alternative Medicine, National Institutes of Health.

Corresponding author and reprints: Marlene P. Freeman, M.D., Women's Mental Health Program, Departments of Psychiatry, Obstetrics and Gynecology, and Nutritional Sciences, University of Arizona College of Medicine, 1501 N. Campbell Ave., P.O. Box 245002, Tucson, AZ 85724-5002 (e-mail: marlenef@email.arizona.edu).