Fatty acids, particularly omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been investigated for their potential role in supporting or treating depression. Several randomized controlled trials (RCTs) and meta-analyses have shown that omega-3 supplementation, especially EPA-predominant formulations, may provide a modest benefit in reducing depressive symptoms, especially in individuals with major depressive disorder (MDD) or those with low baseline omega-3 levels. The proposed mechanisms include anti-inflammatory effects, modulation of neurotransmitter pathways, and alteration of cell membrane fluidity, which may influence neuronal signaling.

However, findings have been inconsistent. Some meta-analyses report small but statistically significant effects, while others indicate minimal or no benefit compared to placebo. The variability in study results may relate to differences in study populations, dosages, EPA/DHA ratios, and baseline dietary intake. Major guidelines, such as those from the American Psychiatric Association, note that omega-3 supplements may be considered as adjunctive treatment for depression, but they are not a primary therapy.

In summary, there is moderate scientific evidence supporting the adjunctive use of fatty acids, particularly omega-3s, for depression. The effect size appears modest, and omega-3s are not sufficient as monotherapy for depression. The evidence for "unspecified" fatty acids (i.e., not limited to omega-3s) is much weaker, and the benefit is primarily attributed to omega-3 PUFAs.