A real-world analysis of antidepressant medications in US veterans aged 60 years and older: a comparative analysis

<b>Aim:</b> To compare the safety and efficacy of antidepressants (AD) among older adults with major depressive disorder (MDD) by assessing treatment change, augmentation and hospitalization rates. <b>Methods:</b> This retrospective study analyzed data from the Veterans Affairs (VA) database, including 142,138 patients aged ≥60 years diagnosed with MDD. Patients prescribed bupropion, citalopram, duloxetine, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline, or venlafaxine were included. Outcomes were treatment change, augmentation and hospitalization rates. Hazard ratios (aHRs) were calculated using sertraline as the reference. <b>Results:</b> Of the patients, 39.6% required augmentation, 18.1% changed antidepressant treatment and 13.3% were hospitalized. The corresponding incidence rate was 544, 124 and 122 events per 1000 person-years. Compared with sertraline, mirtazapine users had the highest AD change risk (aHR 1.34, 95% CI: 1.29-1.40), while duloxetine users had the lowest (aHR 0.87, 95% CI: 0.83-0.92). Duloxetine also had the lowest augmentation risk (aHR 0.89, 95% CI: 0.86-0.92). Mirtazapine users also had the highest risks of augmentation (aHR 1.15, 95% CI: 1.12-1.18) and hospitalization (aHR 1.14, 95% CI: 1.07-1.23). Bupropion had the lowest hospitalization risk (aHR 0.77, 95% CI: 0.71-0.84). <b>Conclusion:</b> Antidepressant choice significantly influences treatment outcomes in older adults with MDD. Duloxetine demonstrated the best profile with the lowest risks of AD change and augmentation, while mirtazapine posed the highest risks of all three outcomes. Personalized treatment strategies are crucial to improving outcomes in this population.