(295) Exposure to Tricyclic and Selective Serotonin Reuptake Inhibitor Antidepressants and The Risk of Hip Fracture: An Updated US-Based Case-Control Study

Publication Number: 626

Background: Historically, studies have reported increased risk of hip fracture following exposure to antidepressants while noting the potential for bias and confounding in this association. With changing patterns of care over time, it is important to update prior studies in other data sources and time periods.

Objectives: To replicate and update a landmark case-control study of the antidepressant-hip fracture association (Hubbard 2003), conducted using UK CPRD over 1987-1999, in a large US claims database with recent data.

Methods: Patients with diagnosis of hip fracture or fractured neck of femur between 2010-01-01 and 2019-12-31 were identified in Optum’s de-identified Clinformatics® Data Mart Database. Index was first recorded fracture for cases. Controls were a random sample of patients with no record of hip fracture and were matched 1:2 on age, sex, and years enrolled. Matched data was analyzed using conditional logistic regression. The impact of first prescriptions was estimated for tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) in days 0-14, 15-42, and 43+ of continuous treatment, allowing for treatment gaps up to 30 days. Potential confounding variables were included in adjusted models if, in bivariate models, inclusion resulted in change of odds ratio (OR) for antidepressants of at least 10%.

Results: 170,738 patients with diagnosis of hip fracture were matched to 295,260 controls. Mean (SD) age of matched cases was 75.6 (15.0) and 67.5% were female. Cohort characteristics were similar to Hubbard. Rates of exposure to TCAs pre-index were 4.24% for cases and 2.76% for controls. Rates for SSRIs pre-index were 22.6% and 14.17%. Rates for TCAs were higher in Hubbard (cases: 17.8%; controls: 11.8%) and lower for SSRIs (5.5% and 3.0%).
History of exposure to opiates was identified as a confounder for both TCAs and SSRIs; history of exposure to benzodiazepines was identified as a confounder for TCAs. Adjusted ORs for days 0-14, 15-42, and 43+ pre-index for TCAs were OR(CI): [2.42(1.93,3.04), 1.90(1.60,2.26), and 1.27(1.23,1.32)], while SSRIs were [1.73(1.47,2.04), 2.24(2.09,2.40), and 1.48(1.46,1.51)]. Corresponding results from Hubbard et al were [4.76(3.06,7.41), 2.58(1.88,3.53), and 1.15 (1.08,1.23)] for TCAs and [6.30(2.65,14.97), 4.30(2.39,7.74), and 1.32(1.19,1.48)] for SSRIs. We hypothesize that reduction in OR magnitude may be due to changes in antidepressant prescribing patterns over time, in particular with an increase in antidepressant prescribing in patients with milder complaints and fewer risk factors for fracture.

Conclusions: In this study, we were able to confirm a positive association between antidepressant use and hip fracture using contemporary data from administrative claims.