Association of Zolpidem With Increased Mortality in Patients With Brain Cancer: A Retrospective Cohort Study Based on the National Health Insurance Service Database.

Abstract

Background and purpose: Zolpidem is one of the most common hypnotics prescribed to treat insomnia worldwide. However, there are numerous reports of a positive association between zolpidem and mortality, including an association with increased cancer-specific mortality found in a Taiwanese cohort study. This study aimed to determine the association between zolpidem use and brain-cancer-specific mortality in patients with brain cancer.

Methods: This population-based, retrospective cohort study analyzed data in the National Health Insurance Service database. All incident cases of brain cancer at an age of ≥18 years at the time of brain cancer diagnosis over a 15-year period (2003-2017) were included. A multivariate Cox regression analysis after adjustment for covariables was performed to evaluate the associations of zolpidem exposure with brain-cancer-specific and all-cause mortality.

Results: This study identified 38,037 incident cases of brain cancer, among whom 11,823 (31.1%) patients were exposed to zolpidem. In the multivariate Cox regression model, the brain-cancer-specific mortality rate was significantly higher in patients who were prescribed zolpidem than in those with no zolpidem prescription (adjusted hazard ratio [HR]=1.14, 95% confidence interval [CI]=1.08-1.21, p<0.001). Zolpidem exposure was significantly associated with increased brain-cancer-specific mortality after adjustment in younger adults (age 18-64 years; adjusted HR=1.37, 95% CI=1.27-1.49) but not in older adults (age ≥65 years; adjusted HR=0.94, 95% CI=0.86-1.02).

Conclusions: Zolpidem exposure was significantly associated with increased brain-cancer-specific mortality in patients with brain cancer aged 18-64 years. Further prospective studies are warranted to understand the mechanism underlying the effect of zolpidem on mortality in patients with brain cancer.