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

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#adult #c-reactive-protein #major-depressive-disorder #dietary-supplements #docosahexaenoic-acids

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

Mischoulon et al., 2022 | J Clin Psychiatry | Rct

Citation

Mischoulon David, Dunlop Boadie W, ... Rapaport Mark Hyman. Omega-3 Fatty Acids for Major Depressive Disorder With High Inflammation: A Randomized Dose-Finding Clinical Trial. J Clin Psychiatry. 2022-Aug-22;83(5). doi:10.4088/JCP.21m14074

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/m2, 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.

Key Findings

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 d

Outcomes Measured

  • C-reactive protein
  • inflammatory markers

Population

Field Value
Population elevated inflammatory markers
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Adult
  • C-Reactive Protein
  • Major Depressive Disorder
  • Dietary Supplements
  • Docosahexaenoic Acids
  • Double-Blind Method
  • Eicosapentaenoic Acid
  • Fatty Acids, Omega-3
  • Female
  • Humans
  • Inflammation
  • Interleukin-6
  • Leukocytes, Mononuclear
  • Male

Evidence Classification

  • Level: Rct
  • Publication Types: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural
  • Vertical: omega-3-mood

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09