Omega-3 Fatty Acids (EPA/DHA)

Class

Essential fatty acids (polyunsaturated fatty acids)

Mechanism

Modulates neuronal membrane fluidity, anti-inflammatory effects, and influences neurotransmitter function including serotonin and dopamine pathways

FDA-Approved Use

Hypertricyceridemia, specifically icosapent ethyl (Vascepa) and omega-3-acid ethyl esters (Lovaza)

Off-Label Use

Augmentation in major depressive disorder (MDD), bipolar depression, cognitive impairment in Alzheimer’s disease (AD) and vascular dementia, agitation and aggression in neurodevelopmental disabilities

Formulation

Oral capsules or liquids, typically EPA-predominant (>60% EPA) formulations preferred for psychiatric uses

Titration

1–4 g/day, dosed according to EPA content and clinical response

Dose Range

1–4 g/day

Kinetics

Absorbed via gastrointestinal tract; incorporated into cell membranes over days to weeks; half-life variable depending on tissue incorporation

Common AEs

Mild gastrointestinal upset, fishy aftertaste or burping

Serious/Rare AEs

Bleeding risk increased in patients on anticoagulants due to mild antiplatelet effect

Monitoring

Monitor for bleeding risk if combined with anticoagulants or antiplatelet agents

Black Box Warning

None

Considerations

Evidence supports cognitive benefit in vascular dementia, aging-related cognitive decline, and recovery post-traumatic brain injury (TBI). May provide modest mood stabilization in multiple sclerosis (MS), Parkinson’s disease (PD), and early dementia syndromes. Use caution in patients on anticoagulants due to increased bleeding risk.