Yeon-Hee Baek1, Hyesung Lee1, Woo Jung Kim2, Jee-Eun Chung3, Nicole Pratt4, Lisa Kalisch Ellett4, Ju-Young Shin5. 1. School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea. 2. Department of Psychiatry, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Gyeonggi-do, South Korea. 3. College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-do, South Korea. 4. Quality Use of Medicines and Pharmacy Research Centre, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia. 5. School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea. Electronic address: shin.jy@skku.edu.
Abstract
OBJECTIVE: To examine the association between benzodiazepine use and the risk of dementia. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study, using a nationwide healthcare database of South Korea (2002-2016). The participants included new users of benzodiazepines aged ≥50 years, with no prior prescription record of benzodiazepines or a history of dementia within the previous 5 years (2002-2006). METHODS: Outcome was defined as an incident dementia with specified algorithms using diagnosis and prescription records, with the application of a 5-year lag-time following the index date during which outcomes were censored. We used a multivariable Cox proportional hazard model to estimate hazard ratio (HR) and the 95% confidence interval (CI). Comorbidities and comedications were treated as time-varying covariates in 90-day windows, and an active comparator was used to reduce potential bias from confounding by indication. Active comparators were defined as new-users of antidepressants. RESULTS: Our final participants included 616,256 patients, after propensity score estimation and matching on a 1:1 ratio. We observed a 23% increase in the risk of dementia in benzodiazepine users, compared with that in nonusers, over a mean follow-up period of 5.5 years (HR 1.23, 95% CI 1.14-1.32). A consistent finding was observed when the lag-time duration was extended to 7 years, revealing a close to null association (HR 1.17, 95% CI 1.04-1.30). When new-users of antidepressants were used as the active comparator, no increase in the risk of dementia with benzodiazepines was observed over 7 years (HR 1.01, 95% CI 0.81-1.27). CONCLUSIONS AND IMPLICATIONS: A significant association was observed between benzodiazepine use and the risk of dementia, compared with nonusers. However, a null or negative association was observed with the use of the active comparator, suggesting the absence of a causal association between dementia and benzodiazepine use.
OBJECTIVE: To examine the association between benzodiazepine use and the risk of dementia. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study, using a nationwide healthcare database of South Korea (2002-2016). The participants included new users of benzodiazepines aged ≥50 years, with no prior prescription record of benzodiazepines or a history of dementia within the previous 5 years (2002-2006). METHODS: Outcome was defined as an incident dementia with specified algorithms using diagnosis and prescription records, with the application of a 5-year lag-time following the index date during which outcomes were censored. We used a multivariable Cox proportional hazard model to estimate hazard ratio (HR) and the 95% confidence interval (CI). Comorbidities and comedications were treated as time-varying covariates in 90-day windows, and an active comparator was used to reduce potential bias from confounding by indication. Active comparators were defined as new-users of antidepressants. RESULTS: Our final participants included 616,256 patients, after propensity score estimation and matching on a 1:1 ratio. We observed a 23% increase in the risk of dementia in benzodiazepine users, compared with that in nonusers, over a mean follow-up period of 5.5 years (HR 1.23, 95% CI 1.14-1.32). A consistent finding was observed when the lag-time duration was extended to 7 years, revealing a close to null association (HR 1.17, 95% CI 1.04-1.30). When new-users of antidepressants were used as the active comparator, no increase in the risk of dementia with benzodiazepines was observed over 7 years (HR 1.01, 95% CI 0.81-1.27). CONCLUSIONS AND IMPLICATIONS: A significant association was observed between benzodiazepine use and the risk of dementia, compared with nonusers. However, a null or negative association was observed with the use of the active comparator, suggesting the absence of a causal association between dementia and benzodiazepine use.