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.
Keywords
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Article info
Publication history
Published online: October 22, 2019
Footnotes
This research was supported by a grant of the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant number: NHCR-HC17C0020). This study was conducted independently of the funder.
This study was approved by the institutional review board of Sungkyunkwan University (No. 2017-08-008), which waived the informed consent, as only de-identified data were used in this study.
The findings of this study were presented at the 2018 Fall International Convention of The Pharmaceutical Society of Korea in Jeju Island, South Korea, on October 19, 2018.
The authors declare no conflicts of interest.
Y.-H.B. and H.L. contributed equally to this work as co-first authors.
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Copyright
© 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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