title: Assessing the cumulative effects of exposure to selected benzodiazepines on the risk of fall-related injuries in the elderly.
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.
authors: Research Centre of CHUM, Montréal and Department of Social and Preventive Medicine, Université de Montréal, Montreal, Quebec, Canada.
authors: Marie-Pierre
authors: MP
authors: Sylvestre
authors: Michal
authors: M
authors: Abrahamowicz
authors: Radan
authors: R
authors: Čapek
authors: Robyn
authors: R
authors: Tamblyn
mesh_terms: D000058:Accidental Falls / Q000706:statistics & numerical data*; D000368:Aged; D000525:Alprazolam / Q000009:adverse effects; D001569:Benzodiazepines / Q000009:adverse effects*; D001960:Bromazepam / Q000009:adverse effects; D002707:Chlordiazepoxide / Q000009:adverse effects; D002998:Clonazepam / Q000009:adverse effects; D005260:Female; D005479:Flurazepam / Q000009:adverse effects; D006801:Humans; D008140:Lorazepam / Q000009:adverse effects; D008297:Male; D016016:Proportional Hazards Models; D012307:Risk Factors; D013693:Temazepam / Q000009:adverse effects
chemical_list: D001569:Benzodiazepines; D002998:Clonazepam; D002707:Chlordiazepoxide; D013693:Temazepam; D005479:Flurazepam; D008140:Lorazepam; D001960:Bromazepam; D000525:Alprazolam