Omega-3 Fatty Acids for Major Depressive Disorder With High Inflammation: A Randomized Dose-Finding Clinical Trial.

Abstract

Objective

This study compared the impact of 3 eicosapentaenoic acid (EPA) doses versus placebo on inflammatory biomarkers and depressive symptoms.

Methods

Sixty-one unmedicated adults (75% female; 45.5 ± 13.8 years) with DSM-5 major depressive disorder (MDD), body mass index > 25 kg/m(2), and plasma high-sensitivity C-reactive protein (hs-CRP) ≥ 3.0 mg/L were randomly assigned to receive epa 1 g/d, 2 g/d, or 4 g/d or placebo for 12 weeks. Prespecified endpoints were a ≥ 0.40 effect size decrease in plasma interleukin (IL)-6, peripheral blood mononuclear cell (PBMC) cytokines, and lipopolysaccharide-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 3 epa doses versus placebo.

Results

In 45 completers, only median PBMC TNF decreased at 2 g/d EPA. No epa dose produced a ≥ 0.35 effect size reduction in plasma IL-6 or mitogen-stimulated TNF. Response rates for epa 4 g/d were 64%, versus 40% for placebo (odds ratio [OR] = 2.63; Cohen d = 0.53), 38% for epa 1 g/d, and 36% for epa 2 g/d (all P > .05). epa 4 g/d showed a significant correlation between percent decrease in plasma hs-CRP and IDS-C30 symptom reduction at 12 weeks (Spearman ρ = 0.691, P = .019).

Conclusions

epa 4 g/d demonstrated a medium effect size for response rates versus placebo. This dose may alleviate MDD in overweight individuals with elevated inflammatory markers, and change in hs-CRP may be correlated with clinical response.

Trial Registration

ClinicalTrials.gov identifier: NCT02553915.