Detection and treatment of long-chain omega-3 fatty acid deficiency in adolescents with SSRI-resistant major depressive disorder

• SSRI-resistant adolescent MDD patients exhibit robust erythrocyte long-chain omega-3 (LCn−3) fatty acid deficits.
• Fish oil supplementation significantly increases erythrocyte LCn−3 fatty acid levels in MDD patients.
• Fish oil supplementation is safe and well-tolerated and may augment SSRI efficacy.
• Additional studies are warranted to further evaluate adjunctive fish oil supplementation as an option for SSRI-resistant MDD patients.

Residual depressive symptoms are commonly observed in adolescents with major depressive disorder (MDD) following treatment with selective serotonin reuptake inhibitors (SSRIs). This study combined a case–control analysis and an open-label fish oil (FO) trial to investigate the relationship between long-chain omega-3 (LCn−3) fatty acid status and residual depressive symptoms in SSRI-resistant adolescent MDD patients. Baseline erythrocyte docosahexaenoic acid (DHA) (−28%, p = 0.0003), but not eicosapentaenoic acid (EPA) (−18%, p = 0.2), was significantly lower in patients (n = 20) compared with healthy controls (n = 20). Patients receiving 10-week low-dose (2.4 g/day, n = 7) and high-dose (16.2 g/day, n = 7) FO exhibited significant increases in erythrocyte EPA and DHA composition. In the intent-to-treat sample, depressive symptoms decreased significantly in the high-dose group (n = 7, −40%, p < 0.0001), and there was a trend in the low-dose group (n = 10, −20%, p = 0.06). Symptom remission was observed in 40% of patients in the low-dose group and 100% of patients in the high-dose group. There were no significant changes in vital signs and adverse events were rated as mild or moderate in severity. These preliminary findings demonstrate that adolescents with SSRI-resistant depression exhibit robust DHA deficits, and suggest that adjunctive FO supplementation is well-tolerated and effective for increasing LCn−3 fatty acid status and augmenting SSRI antidepressant effects.

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