Longitudinal patterns of antidepressant and benzodiazepine use associated with injurious falls in older adults with depression: a retrospective cohort study.

Background: Cross-sectional studies have shown that antidepressants (ADs) and benzodiazepines (BZDs) are commonly co-prescribed for depression, potentially increasing the risk of falls and related injuries (FRI) compared to monotherapies. However, little is known about the longitudinal dosing patterns (i.e., trajectory) of ADs and BZDs and their associated FRI risk.

Methods: This retrospective cohort study used group-based multi-trajectory models to identify AD-BZD trajectories among older Medicare fee-for-service beneficiaries with depression initiating ADs with/without BZDs. We measured the standardized daily doses of AD and BZD within 84 days after AD initiation and categorized them into negligible, very-low, low, moderate, high, or very-high levels with a discontinuing, declining, increasing, or stable trend. Then, we assessed the subsequent 12-month FRI risk associated with each trajectory.

Results: Among 102,750 eligible beneficiaries, the mean age was 75.5 years (SD = 7.5); 67.0% were female, 81.2% were White, and 4.9% experienced an FRI. We identified 12 distinct AD/BZD trajectories, of which 79,424 patients received AD monotherapy, and 23,326 patients received both ADs and BZDs. Compared with Group A (low discontinuing AD; 17.3% of the cohort; FRI crude incidence rate = 99.7/1000 person-year), trajectories with a higher dose or a longer duration of AD use were associated with an increased FRI risk, regardless of BZD use. The hazard ratios (HR) and 95% confidence intervals (CI) for Groups B (low declining AD; 31.0% of the cohort), C (moderate increasing AD; 23.5%), and D (high increasing AD; 5.4%) were 1.11 (1.04-1.19), 1.24 (1.16-1.32), and 1.29 (1.16-1.42), respectively. Combining ADs and BZDs at very-low doses or with declining trends did not significantly alter FRI risk compared to AD monotherapy. However, FRI risk increased when BZDs were used at low doses (either with stable or increasing trends). The HR and 95%CI for Groups J (moderate increasing AD/low stable BZD, 1.3%) and L (very-high increasing AD/low-dose increasing BZD) were 1.71 (1.41, 2.08) and 1.96 (1.53, 2.49), respectively.

Conclusions: We observed a dose-response relationship between AD use and FRI risk, independent of BZD use, highlighting the importance of initiating ADs at the lowest effective dose and closely monitoring to prevent FRI.