Pharmacogenomic-guided treatment showed age-dependent cognitive benefits in depressive disorder patients.

BACKGROUND: Pharmacogenomic testing may optimize antidepressant treatment in depression. Its effects on cognition and across age groups remain unclear. METHODS: A total of 843 patients with depressive disorder were stratified by age (adolescent, young adult, middle-aged, elderly) and assigned to pharmacogenomic-guided or treatment-as-usual groups. Guided treatment was based on pharmacogenomic results. Primary outcomes were changes in Montreal Cognitive Assessment (MoCA), remission (HDRS<8), and response (≥50 % HDRS reduction) at weeks 4, 8, and 12. RESULTS: MoCA improvement inversely correlated with age (week 8: r = -0.078, P = 0.036; week 12: r = -0.076, P = 0.041). Pharmacogenomic guidance was associated with greater cognitive gains in younger participants, with sustained improvement in adolescents (all P ≤ 0.036), improvement in young adults at weeks 8 and 12 (both P ≤ 0.013), and transient benefit in middle-aged patients at week8 (P = 0.048). No cognitive benefit was observed in the elderly. Multi-way ANOVA for depressive symptoms (HDRS) revealed a Group × Time interaction (P < 0.001), and for cognitive function (MoCA) showed both a Group × Time interaction (P = 0.011) and an Age × Time interaction (P = 0.024), consistent with age-dependent recovery trajectories. Pharmacogenomic guidance was associated with increased remission and response rates from week 8 through week 12 across all ages. LIMITATIONS: single blinded; single-center design. CONCLUSIONS: Pharmacogenomic-guided treatment consistently improves depressive symptom remission but shows age-dependent cognitive effects: sustained in youth, transient in middle age, absent in elderly. Age is a key modifier of cognitive benefit, supporting prioritized use in younger patients, while elderly individuals may require integrated interventions beyond pharmacogenomics.