Personalized Eicosapentaenoic Acid Therapy for Clinical Depression

Major depressive disorder (MDD) is a leading global cause of disability, and current antidepressant treatments remain inadequate for many patients. Emerging evidence highlights the role of inflammation in the pathophysiology of depression, offering a novel therapeutic target. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid (n-3 PUFA) with potent anti-inflammatory and pro-resolving effects, shows promise as an adjunctive treatment for depression. This article examines the rationale behind EPA's antidepressant effects and explores the potential for personalized EPA therapy to enhance treatment outcomes. A daily dose of at least 1 g of pure EPA or an EPA/docosahexaenoic acid formulation with a ratio greater than 2:1 in favor of EPA is recommended alongside standard antidepressant therapy. Factors such as inflammatory status, psychiatric and medical comorbidities, endogenous n-3 PUFA status, and genetic polymorphisms, should be considered to optimize the therapeutic response. EPA's anti-inflammatory, pro-resolving, and neuroprotective properties make it a compelling option for personalized treatment strategies in MDD. [ Psychiatr Ann . 2025;55(2):e28–e33.]