Risk of Dementia in Long-Term Benzodiazepine Users: Evidence from a Meta-Analysis of Observational Studies

J Clin Neurol. 2019 Jan;15(1):9-19. doi: 10.3988/jcn.2019.15.1.9. Epub 2018 Oct 26.


Background and purpose: There is conflicting evidence in the literature on the association between benzodiazepines (BDZs) and the risk of dementia. This meta-analysis aimed to determine the relationship between the long-term usage of BDZs and the risk of dementia.

Methods: The PubMed and Embase databases were systematically searched for relevant publications up to September 2017. The literature search focused on observational studies that analyzed the relationship between the long-term use of BDZs and the risk of dementia. Pooled rate ratios (RRs) with 95% confidence interval (CI) were assessed using a random-effects model. The robustness of the results was checked by performing subgroup and sensitivity analyses.

Results: Ten studies were included: six case-control and four cohort studies. The pooled RR for developing dementia was 1.51 (95% CI=1.17-1.95, p=0.002) in patients taking BDZ. The risk of dementia was higher in patients taking BDZs with a longer half-life (RR=1.16, 95% CI=0.95-1.41, p=0.150) and for a longer time (RR=1.21, 95% CI=1.04-1.40, p=0.016).

Conclusions: This meta-analysis that pooled ten studies has shown that BDZ significantly increases the risk of dementia in the elderly population. The risk is higher in patients taking BDZ with a longer half-life (>20 hours) and for a longer duration (>3 years).

Keywords: benzodiazepines; dementia; meta-analysis.