Eicosapentaenoic acid as an add-on to antidepressant medication for co-morbid major depression in patients with diabetes mellitus: A randomized, double-blind placebo-controlled study

Background: Depression is common in individuals with diabetes. The present study is the first randomized controlled trial to test the efficacy of omega-3 ethyl-eicosapentaenoic acid (E-EPA) as adjuvant to antidepressant medication in the treatment of depression in adults with diabetes mellitus. Methods: In the VU University Medical Center, we conducted a 12-week, placebo-controlled, double-blind, parallel-group intervention study of E-EPA (1 g/day) versus placebo in 25 diabetes patients meeting DSM-IV criteria for major depressive disorder, who were already using antidepressant medication. The primary outcome was severity of depressive symptoms, assessed by the Montgomery Asberg Depression Rating Scale (MADRS) at baseline and 12-week follow-up at two-weekly intervals. Blood samples were collected at baseline and at 12-week follow-up to determine EPA levels in erythrocyte membranes. Data were analyzed with ANOVA for repeated measures. Results: Thirteen participants were randomly assigned to E-EPA; 12 participants were given placebo. At 12-week follow-up, erythrocyte membranes from patients receiving E-EPA contained tripled levels of EPA, while no changes were noted in participants receiving placebo. In both groups, depressive symptoms significantly decreased over time (F=21.14, p<0.001), yet no significant differences were found between those treated with E-EPA versus placebo (F = 1.63, p = 0.17). Limitations: Although having sufficient study power, this study had a relatively small sample size. Small effects could not be detected, and dose-dependent effects could not be studied. Conclusions: No evidence was found for the efficacy of adding E-EPA to antidepressants in reducing depressive symptoms in diabetic patients with co-morbid depression. 2010 Elsevier B.V. All rights reserved.