Association Between Antidepressant-Benzodiazepine Longitudinal Use Trajectories and the Risk of Fall and Related Injuries Among Older Adults With Depression

OBJECTIVES: To investigate antidepressant (AD) and benzodiazepine (BZD) trajectories and their associated risk of fall and related injuries (FRI) among older adults with depression.

METHODS: In a retrospective cohort study, we identified 12-month AD-BZD trajectories among older Medicare beneficiaries initiating ADs and/or BZDs. We categorized their standardized daily doses into negligible (AD:<0.1 defined daily dose [DDD], BZD:<1 diazepam milligram equivalent [DME]), very-low (AD:0.1 to <0.5 DDD, BZD:1 to <10 DME), low (AD:0.5 to <1 DDD, BZD:10 to <20 DME), moderate (AD:1 to <1.5 DDD, BZD:20 to <40 DME), high (AD:1.5 to <2 DDD, BZD:40 to <60 DME), and very-high (AD:≥ 2 DDD, BZD:≥ 60 DME). We applied stabilized inverse probability treatment weighting and Cox proportional hazards models to assess the association between trajectory membership and 12-month FRI risk.

RESULTS: Among 32,203 participants (mean age=75.3 years [SD=7.4], 32.7% male, 81.0% White), we identified 8 AD/BZD trajectories. Compared with Group A: very-low-dose discontinuing AD/very-low-dose discontinuing BZD (FRI incidence=92.1/1000 person-year), moderate- to very-high-dose increasing AD use was associated with an increased FRI risk (HR=1.31; 95%CI=1.02, 1.69), regardless of BZD use. Combination of low- to high-dose increasing AD with low-dose stable BZD also led to a higher FRI risk, with HRs ranging from 1.85 (95%CI=1.41, 2.42) to 2.30 (95%CI=1.72, 3.07).

CONCLUSIONS: Among older Medicare beneficiaries with depression initiating ADs and/or BZDs, we observed a dose-response relationship between AD use and FRI risk, irrespective of BZD dose. Our findings highlight the importance of initiating ADs at the lowest effective dose in older adults with depression and emphasize the need for careful evaluation and vigilant monitoring to prevent FRI.