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

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.