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Assessing the cumulative effects of exposure to selected benzodiazepines on the risk of fall-related injuries in the elderly

Published online by Cambridge University Press:  08 November 2011

Marie-Pierre Sylvestre ,
Michal Abrahamowicz ,
Radan Čapek  and
Robyn Tamblyn
Marie-Pierre Sylvestre
Affiliation:
Research Centre of the CHUM, Montréal and Department of Social and Preventive Medicine, Université de Montréal, Montreal, Quebec, Canada
Michal Abrahamowicz*
Affiliation:
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
Radan Čapek
Affiliation:
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
Robyn Tamblyn
Affiliation:
Departments of Medicine and of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
*
Correspondence should be addressed to: Michal Abrahamowicz, Department of Epidemiology and Biostatistics, McGill University, 687 Pine Avenue West, V-Pavilion, Montreal, QC H3A 1A1, Canada. Phone: +1 514-934-1934 ext. 44712; Fax: +1 514-934-8293. Email: [email protected].
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Abstract

Background: The use of benzodiazepines is associated with increased risk of fall-related injuries in the elderly. However, it is unclear if the risks vary across the products and how they depend on the pattern of use and dosage. Specifically, the possibility of cumulative effects of past benzodiazepine use has not been thoroughly investigated.

Methods: We used the administrative database for a cohort of 23,765 new users of benzodiazepines, aged 65 years and older, in Quebec, Canada, between 1990 and 1994. The associations between the use of seven benzodiazepines and the risk of fall-related injuries were assessed using several statistical models, including a novel weighted cumulative exposure model. That model assigns to each dose taken in the past a weight that represents the importance of that dose in explaining the current risk of fall.

Results: For flurazepam, the best-fitting model indicated a cumulative effect of doses taken in the last two weeks. Uninterrupted use of flurazepam in the past months was associated with a highly significant increase in the risk of fall-related injuries (HR = 2.83, 95% CI: 1.45–4.34). The cumulative effect of a 30-day exposure to alprazolam was 1.27 (1.13–1.42). For temazepam, the results suggested a potential withdrawal effect.

Conclusions: Mechanisms affecting the risk of falls differ across benzodiazepines, and may include cumulative effects of use in the previous few weeks. Thus, benzodiazepine-specific analyses that account for individual patterns of use should be preferred over simpler analyses that group different benzodiazepines together and limit exposure to current use or current dose.

Keywords

benzodiazepineselderlyinjuriescumulative exposureproportional hazards modeltime-dependent covariates
Type
Research Article
Information
International Psychogeriatrics , Volume 24 , Issue 4 , April 2012 , pp. 577 - 586
Copyright
Copyright © International Psychogeriatric Association 2011

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