A 5-Year Prospective Assessment of the Risk Associated with Individual Benzodiazepines and Doses in New Elderly Users

Authors

  • Robyn Tamblyn PhD,

    1. From the Departments of *Medicine, Epidemiology and Biostatistics, and Pharmacology, McGill University, Montreal, Quebec, Canada.
    Search for more papers by this author
  • Michal Abrahamowicz PhD,

    1. From the Departments of *Medicine, Epidemiology and Biostatistics, and Pharmacology, McGill University, Montreal, Quebec, Canada.
    Search for more papers by this author
  • Roxane du Berger MSc,

    1. From the Departments of *Medicine, Epidemiology and Biostatistics, and Pharmacology, McGill University, Montreal, Quebec, Canada.
    Search for more papers by this author
  • Peter McLeod MD,

    1. From the Departments of *Medicine, Epidemiology and Biostatistics, and Pharmacology, McGill University, Montreal, Quebec, Canada.
    Search for more papers by this author
  • Gillian Bartlett PhD

    1. From the Departments of *Medicine, Epidemiology and Biostatistics, and Pharmacology, McGill University, Montreal, Quebec, Canada.
    Search for more papers by this author

  • This study was funded by the Fonds de recherche en santé du Québec and approved by the McGill University Faculty of Medicine Institutional Review Board, the Quebec Access to Information Commission, and the Régie de l'assurance maladie du Québec. R. Tamblyn is a Canadian Institutes for Health Research Scientist and a William Dawson Scholar. M. Abrahamowicz is a James McGill Professor. G. Bartlett is a Canadian Institutes for Health Research New Investigator for the New Emerging E-Integration Team.

Dr. Robyn Tamblyn, Faculty of Medicine, McGill University, 1140 Pine Ave W., Montreal, Quebec, Canada H3A 1A3. E-mail: robyn.tamblyn@mcgill.ca

Abstract

Objectives: To determine the risk of injury associated with the new use of individual benzodiazepines and dosage regimens in the elderly.

Design: Prospective database cohort study with 5 years of follow-up.

Setting: Quebec, Canada.

Participants: Two hundred fifty-three thousand two hundred forty-four persons aged 65 and older who were nonusers of benzodiazepines in the year before follow-up.

Measurements: Population-based hospitalization and prescription and medical services claims databases were used to compare the risk of injury during periods of benzodiazepine use with those of nonuse. Periods of use were measured for 10 insured benzodiazepines by drug and dose as time-dependent covariates. Injury was defined as the first occurrence of a nonvertebral fracture, soft-tissue injury, or accident-related hospital admission. Patient age, sex, previous injury history, concomitant medication use, and comorbidity were measured as fixed and time-dependent confounders. Cox proportional hazards models were used to estimate the risk of injury with benzodiazepine use and to determine the extent to which patient characteristics, differences in dosage, or in the effect of increasing dosage for individual drugs explained differences between drugs.

Results: More than one-quarter (27.6%) of 253,244 elderly were dispensed at least one prescription for a benzodiazepine, and 17.7% of elderly were treated for at least one injury during follow-up, of which fractures were the most common. Patient characteristics, systematic differences in the risk of injury in elderly prescribed different benzodiazepines, and differences in dosage prescribed for individual drugs confounded the risk of injury with benzodiazepine use. The risk of injury with increasing dosage varied by drug from a hazard ratio of 0.92 (95% confidence interval (CI)=0.60, 1.42) for alprazolam to 2.20 (95% CI=1.39, 3.47) for flurazepam per 1 standardized adult dose increase.

Conclusion: The risk of injury varied by benzodiazepine, independent of half-life, as did the risk associated with increasing dosage for individual products. Higher doses of oxazepam, flurazepam, and chlordiazepoxide are associated with the greatest risk of injury in the elderly.

Ancillary