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Omega-3 Fatty Acid Augmentation of Citalopram Treatment for Patients With Major Depressive Disorder

Gertsik, Lev MD*†; Poland, Russell E. PhD†‡; Bresee, Catherine MS; Rapaport, Mark Hyman MD†§

Journal of Clinical Psychopharmacology: February 2012 - Volume 32 - Issue 1 - p 61–64
doi: 10.1097/JCP.0b013e31823f3b5f
Original Contributions

Objective The objective of this study was to explore the efficacy of combination therapy with citalopram plus omega-3 fatty acids versus citalopram plus placebo (olive oil) in the initial treatment of individuals with major depressive disorder (MDD). We hypothesized that combination therapy would lead not only to greater efficacy but also to a more rapid onset of therapeutic response.

Methods Forty-two subjects participated in this 9-week randomized, masked, placebo-controlled study of combination therapy (two 1 g capsules containing a blend of 900 mg of eicosapentaenoic acid, 200 mg of and docosahexaenoic acid, and 100 mg of other omega-3 fatty acids twice daily plus citalopram) versus monotherapy (two 1 g capsules of olive oil per day plus citalopram) treatment of MDD.

Results The combination therapy demonstrated significantly greater improvement in Hamilton Depression Rating scale scores over time (F = 7.32; df 1,177; P = 0.008) beginning at week 4 (t = −2.48; df 177; P = 0.014).

Conclusions Combination therapy was more effective than monotherapy in decreasing signs and symptoms of MDD during the 8 weeks of active treatment; however, combination therapy did not seem to enhance the speed of the initial antidepressant response. These findings suggest that there may be an advantage to combining omega-3 fatty acids with a selective serotonin uptake inhibitor in the initial treatment of individuals with MDD. A larger definitive study is warranted.

From the *California Clinical Trials Medical Group, Glendale; †Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, CA; ‡Department of Psychiatry and Behavioral Sciences,Meharry Medical College, Nashville, TN; and §Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Received November 19, 2010; accepted after revision July 24, 2011.

Reprints: Lev Gertsik, MD, Medical Director, California Clinical Trials Medical Group, 1560 E Chevy Chase Dr, Suite 140, Glendale, CA 91206 (e-mail:

This study was funded through the National Institutes of Health’s National Center for Complementary and Alternative Medicine (R21-AT001077) and the National Center for Research Resources (M01-RR000425).

© 2012 Lippincott Williams & Wilkins, Inc.