Comparing Effectiveness of Antidepressants for Nursing Home Residents With Dementias and Depressive Symptoms

Alzheimer's disease and related dementias (ADRD) are frequently accompanied by depressive symptoms, which may accelerate cognitive decline and increase mortality. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are commonly prescribed, yet comparative effectiveness evidence in nursing home residents with ADRD is scarce.

We conducted a retrospective cohort study using linked CMS data (2011-2018) of long-stay nursing home residents aged ≥ 65 years with ADRD and baseline depressive symptoms who newly initiated an SSRI or SNRI. Depressive symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9; self-report or observed) at baseline and 60-120 days after initiation. Outcomes were the change in PHQ-9 scores (continuous) and clinically meaningful improvement. Analyses used overlap propensity score and inverse probability of censoring weighted linear and log-binomial models with generalized estimating equations to account for clustering of nursing home residents. Intention-to-treat (ITT) analyses, as-treated, and subgroup analyses were conducted.

Among 19,397 SSRI initiators and 2581 SNRI initiators, 66.9% had mild depressive symptoms at baseline. Median time from initiation to follow-up assessment was 85 days. In ITT analyses, mean PHQ-9 change was -2.38 for SSRIs and -2.24 for SNRIs (adjusted difference: -0.15; 95% CI, -0.42 to 0.11); clinically meaningful improvement occurred in 55.2% versus 56.9% (risk difference: -1.57; 95% CI, -3.66 to 0.52). As-treated analyses yielded similar results, and findings were consistent across subgroups defined by baseline depression severity, cognitive function, dementia type, and sensitivity analyses.

SSRIs and SNRIs were similarly effective for depressive symptoms in nursing home residents with ADRD. Given this and modest improvement rates, antidepressant selection should be individualized, emphasizing safety and resident characteristics. Additional research is needed to inform the decision to treat or not to treat, specific medication selection, and when to stop treatment in this population.