Omega-3 Fatty Acids for Major Depressive Disorder With High Inflammation

Abstract

Objective: We compared the impact of three eicosapentaenoic acid (EPA) doses versus placebo on inflammatory biomarkers and depressive symptoms. Methods: We randomized 61 unmedicated adults (75% female; 45.5 ± 13.8 years) with DSM-5 major depressive disorder (MDD), body mass index (BMI) >25 kg/m2, and plasma high-sensitivity C-Reactive Protein (hs-CRP) ≥3.0 mg/L to EPA 1 g/day, 2 g/day, 4 g/day or placebo for 12 weeks. Prespecified endpoints were a ≥.40 effect size decrease in plasma interleukin (IL)-6, peripheral blood mononuclear cell (PBMC) cytokines, and lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) production. Response was defined as a ≥50% decrease of Inventory of Depressive Symptomatology, Clinician-Rated version (IDS-C30) scores. We compared outcomes for the three EPA doses versus placebo. Results: In 45 completers, only median PBMC TNF decreased at 2 g/day EPA. No EPA dose produced a ≥.35 ES reduction in plasma IL-6 or mitogen-stimulated TNF. Response rates for EPA 4 g/day were 64%, versus 40% for placebo (odds ratio [OR]= 2.63; Cohen d = 0.53), 38% for EPA 1 g/day and 36% for EPA 2 g/day (all P>0.05). EPA 4 g/day showed a significant correlation between percent decrease in plasma hs-CRP and IDS-C30 symptom reduction at 12 weeks (Spearman rho=0.691, p=0.019). Conclusion: EPA 4 g/day demonstrated a medium effect size for response rates versus placebo. This dose may alleviate MDD in overweight individuals with elevated inflammatory markers, and hs-CRP may be correlated with clinical response.