Injurious Fall Risk Differences Among Older Adults With First-Line Depression Treatments

Importance: One-third of older adults in the US have depression, often treated with psychotherapy and antidepressants. Previous studies suggesting an increased risk of falls and related injuries (FRI) associated with antidepressant use may be affected by confounding by indication or immortal time bias. Objective: To evaluate the association between FRI risk and first-line treatments in older adults with depression. Design, Setting, and Participants: This cohort study used a target trial emulation framework with a cloning-censoring-weighting approach with Medicare claims data from 2016 to 2019. Participants included fee-for-service beneficiaries aged 65 years or older with newly diagnosed depression. Data were analyzed from October 1, 2023, to March 31, 2024. Exposures: First-line depression treatments including psychotherapy, sertraline, escitalopram, citalopram, mirtazapine, duloxetine, trazodone, fluoxetine, bupropion, paroxetine, and venlafaxine. Main Outcome and Measure: One-year FRI rate, restricted mean survival time (RMST), and adjusted hazard ratio (aHR) with 95% CI. Results: Among 101 953 eligible beneficiaries (mean [SD] age, 76 [8] years), 63 344 (62.1%) were female, 7404 (7.3%) were Black individuals, and 81 856 (80.3%) were White individuals. Compared with the untreated group, psychotherapy use was not associated with FRI risk (aHR, 0.94 [95% CI, 0.82-1.17]), while other first-line antidepressants were associated with a decreased FRI risk (aHR ranged from 0.74 [95% CI, 0.59-0.89] for bupropion to 0.83 [95% CI, 0.67-0.98] for escitalopram). The FRI incidence ranged from 63 (95% CI, 53-75) per 1000 person-year for those treated with bupropion to 87 (95% CI, 83-90) per 1000 person-year for those who were untreated. The RMST ranged from 349 (95% CI, 346-350) days for those who were untreated to 353 (95% CI, 350-356) days for those treated with bupropion. Conclusions and Relevance: In this cohort study of older Medicare beneficiaries with depression, first-line antidepressants were associated with a decreased FRI risk compared with untreated individuals. These findings provide valuable insights into their safety profiles, aiding clinicians in their consideration for treating depression in older adults.