Major depressive disorder (MDD) is a complex condition involving alterations in several interconnected biological systems. Omega-3 polyunsaturated fatty acids, particularly EPA and DHA, have gained increasing attention as potential adjunctive strategies for depression.

Their effects appear to extend beyond the brain alone. Omega-3 fatty acids can influence the gut–brain axis by modulating gut microbiota composition, intestinal permeability, immune responses, and signalling between the gut and the brain. At the same time, they may help reduce inflammation, support neuronal membrane function, and influence neurotransmission, synaptic plasticity, and neurogenesis.

Through these multiple and interconnected effects, omega-3 fatty acids may help restore balance across biological pathways altered in depression, supporting their potential role as an add-on strategy for MDD.