All-cause mortality with use of antidepressants and benzodiazepines after major osteoporotic fracture

Objectives: to study the association between use of antidepressants and benzodiazepines and the risk of mortality after major osteoporotic fracture (MOF). Fractures of hip, humerus, forearm and spine were considered as a MOF. Methods: A cohort study was performed within the Dutch PHARMO Database. All patients aged 65 years or older with a first record of a MOF between 2002 and 2011 were included. Oral use of antidepressants and benzodiazepines was determined using pharmacy dispensing data. Cumulative incidences and adjusted hazard ratios were estimated with Kaplan Meier analyses and Cox-proportional hazards models, respectively. Time-dependent adjustments were made for age, sex, comorbidity and concomitant drug use. Results: A total of 4854 patients sustained a MOF. The cumulative incidence of use of antidepressants following the first fracture increased significantly from 10.6% (95% CI 9.8-11.6%) at 3 months to 14.7% (95% CI 13.7-15.7%) at 12 months; for benzodiazepines it increased significantly from 24.0% (95% CI 22.8-25.3%) at 3 months to 31.4% (95% CI 30.1-32.8%) at 12 months. After a major osteoporotic fracture, current use of antidepressants or benzodiazepines was not associated with all-cause mortality compared to no use of antidepressants and benzodiazepines (adjusted HR 0.96 (95% CI 0.76-1.21) and 1.16 (95% CI 0.96-1.41) respectively). In contrast, all-cause mortality was significantly increased after a MOF among patients who previously used but stopped taking antidepressants (defined as the most recent dispensing more than 3 months ago) [adjusted HR 1.39 (95% CI 1.15-1.66)] or benzodiazepines [adjusted HR 1.20 (95% CI 1.02-1.42)]. Conclusion: This study did not show an association between mortality risk and current use of antidepressants or benzodiazepines after a MOF. However, risk of mortality increased after cessation of antidepressants or benzodiazepines. Patients with a MOF and previous antidepressant or benzodiazepine therapy should be monitored for reasons that increase mortality in order to elucidate these findings.