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Comparative Study
. 2025 Feb;14(2):e240187.
doi: 10.57264/cer-2024-0187. Epub 2025 Jan 21.

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

Ryan D Pittman  1   2 , S Scott Sutton  1   2 , Joseph Magagnoli  1   2 , Tammy H Cummings  1   2
Affiliations
Comparative Study

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

Ryan D Pittman et al. J Comp Eff Res. 2025 Feb.

Abstract

Aim: 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. Methods: 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. Results: 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). Conclusion: 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.

Keywords: antidepressants; augmentation; depression; hospitalization; medication changing.

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Conflict of interest statement

Competing interests disclosure

SS Sutton has received research grants from Boehringer Ingelheim, Gilead, EMD Serono and Alexion Pharmaceuticals, all for projects unrelated to study. SS Sutton, J Magagnoli and TH Cummings disclose support from NIH grant R01DA054992 and the South Carolina Center for Rural and Primary Healthcare for projects unrelated to this study. The authors have no other competing interests or relevant affiliations with any organization/entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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