Omega-3 Fatty Acids Offer No Therapeutic Advantage Over Placebo for Adolescent Depression

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These results challenge existing conceptions that omega-3 fatty acids may be effective in treating adolescent major depressive disorder.

Results of a double-blind, placebo-controlled study published in the Journal of Clinical Psychiatry suggest that omega-3 fatty acids (O3FA) are not superior to placebo as monotherapy for adolescents with major depressive disorder.

Adolescents (age 12-19 years; 57% girls) diagnosed with major depressive disorder were randomly assigned to either O3FA (n=24) or placebo (n=27) for 10 weeks ( identifier: NCT00962598). Both agents were administered at an initial dose of 1.2 g/day, titrated up to a maximum dose of 3.6 g/day in 0.6-g/day increments every 2 weeks. Participants were not taking any psychotropic medications during the study period. Investigators captured depression severity using clinician ratings on the Children’s Depression Rating Scale-Revised and self-ratings on the Beck Scale for Suicide Ideation. Participants were also monitored for dietary intake, study compliance, and adverse events.

O3FA had no significant clinical advantages compared with placebo on any clinical feature, including depression severity and levels of anhedonia, irritability, and suicidality. Both groups reported improvements in clinician-rated depression severity (O3FA, P <.001; placebo, P <.00) and in self-rated suicidality (O3FA, P <.001; placebo, P =.002) during the study period. Using clinician-rated depression scale scores, 42.9% of O3FA recipients and 50.0% of placebo recipients were classified as “treatment responders,” although no significant differences in response levels were identified between groups (P =.63). Both groups experienced similar improvements in the depression subcategories of irritability (both P <.001) and anhedonia (O3FA, P =.001; placebo, P <.001). No significant adverse events were observed for either medication at any dose.

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These results challenge existing conceptions that O3FA monotherapy may be effective in treating adolescent major depressive disorder. However, the small sample size and heterogenous nature of the study population may have limited this analysis. Future studies are necessary to elucidate the precise advantages, if any, offered by O3FA therapy.


Gabbay V, Freed RD, Alonso CM, et al. A double-blind placebo-controlled trial of omega-3 fatty acids as a monotherapy for adolescent depression. J Clin Psychiatry. 2018;79(4):17m11596.