A Meta-Analytic Review of Double-Blind, Placebo-Controlled Trials of Antidepressant Efficacy of Omega-3 Fatty Acids

Pao-Yen Lin, M.D., Ph.D., and Kuan-Pin Su, M.D.

Objective: Evidence has indicated an association between depression and low dietary intake of omega-3 polyunsaturated fatty acids (PUFAs). However, clinical trials examining the therapeutic benefit of omega-3 PUFAs in depression showed inconsistent results. The goal of this study is to systematically evaluate the antidepressant efficacy of omega-3 PUFAs by using meta-analytic method.

Data Sources: MEDLINE, Embase, and PsycINFO databases were searched from 1966 through August 2006 using the key words (depression OR depressive disorder OR mood disorder) AND (omega-3 OR EPA OR DHA OR polyunsaturated fatty acid OR fish oil). The search was limited to literature in English and clinical trials.

Study Selection: Ten double-blind, placebo-controlled studies in patients with mood disorders receiving omega-3 PUFAs with the treatment period lasting 4 weeks or longer were included.

Data Extraction: Effect size (ES) of each individual study was derived by computing the standardized mean difference. A random-effects model was used to pool the ESs of all included studies.

Data Synthesis: When pooling the results of 10 included studies (N = 329), we found a significant antidepressant effect of omega-3 PUFAs (ES = 0.61, p = .003). Likewise, omega-3 PUFAs significantly improved depression in patients with clearly defined depression (ES = 0.69, p = .002) or with bipolar disorder (ES = 0.69, p = .0009). The dosage of eicosapentaenoic acid (EPA) did not change the antidepressant efficacy significantly. However, significant heterogeneity among these studies and publication bias were noted.

Conclusions: Although our meta-analysis showed significant antidepressant efficacy of omega-3 PUFAs, it is still premature to validate this finding due to publication bias and heterogeneity. More large-scale, well-controlled trials are needed to find out the favorable target subjects, therapeutic dose of EPA, and the composition of omega-3 PUFAs in treating depression.

(J Clin Psychiatry 2007;68:1056-1061)

Received April 17, 2006; accepted Dec. 7, 2006. From the Department of Psychiatry, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan (Dr. Lin); and the Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan, and the Stress, Psychiatry, and Immunology Laboratory (SPI-Lab), Institute of Psychiatry, King's College London, London, United Kingdom (Dr. Su).

This work was supported by grants DOH 94F044 and DOH 95F022 from the Taiwan Department of Health; and grants DMR-92-92 and DMR-94-046 from China Medical University Hospital, Taichung, Taiwan.

The authors report no additional financial or other relationships relevant to the subject of this article.

Corresponding author and reprints: Kuan-Pin Su, M.D., Department of General Psychiatry, China Medical University Hospital, No. 2, Yuh-Der Rd., Taichung 404, Taiwan (e-mail: cobolsu@gmail.com).