Patterns of benzodiazepine use and risk of injury in the elderly

Background. Benzodiazepines are sedative-hypnotic medications frequently prescribed in elderly patients for several clinical indications. An association with increased risk for falls has been reported but there is continued debate regarding which specific benzodiazepines are associated with this risk.Objectives. To estimate the risk of injuries from falls associated with benzodiazepine use in an elderly cohort taking into account patient characteristics and changes in patterns of use over time.Methods. Using information from provincial administrative health databases, 462,543 community-dwelling, 66 year old Quebec residents were screened for benzodiazepine use in 1989. Subjects who did not use benzodiazepines in 1989 were observed for the next five years to estimate incidence rates and evaluate patient characteristics associated with new use for thirteen benzodiazepines. Patterns of use for incident users were characterized in terms of duration, dose and frequency of switching or adding benzodiazepines. New methods were developed to model the past cumulative dose and duration of benzodiazepine exposure. The impact of benzodiazepine exposure on risk of injury was estimated using Cox proportional hazards analyses with time-dependent covariates to take into account changes in dose and patterns of use.Results. The overall incidence rate for benzodiazepines was 88.7 per 1,000 person-years, with higher rates in women (95.0) than men (81.8). Predictors of incident use were different in individual products and there were systematic differences between users and non-users. Use of anti-depressants in 1989 was the strongest predictor for incident benzodiazepine use (HR 1.45 to 3.07, p < 0.0001). The median duration for uninterrupted periods of use was 31 days (mean = 75.5 days, sd = 137.2). The mean dose was almost half the recommended maximum adult daily dose and only 8.6% of subjects exceeded the maximum. Older age at date of first prescription significantly increased the likelihood of increasing duration and dose overtime (OR = 1.02, p < 0.0001). All benzodiazepines except clonazeparn were significantly associated with an increased risk of injuries from falls (p < 0.05). The best predictive model for most benzodiazepines included a cumulative measure of duration and current dose.Conclusion. Benzodiazepines are associated with an increased risk of injuries from falls in elderly patients, however duration of exposure may be more critical than dose. Physiological dependence and withdrawal symptoms appear to play an important role in increasing the risk for many benzodiazepines