Use of Sedative-Hypnotics and Mortality: A Population-Based Retrospective Cohort Study

Study Objectives: Researchers have previously reported a possible association between sedative-hypnotics and increased mortality. However, the relationship remains controversial. We investigated the association between sedative-hypnotics and mortality using a large population-based database from the Republic of Korea. Methods: We used a National Health Insurance Service database. The study population was a 5% random sample of the database from the years 2002-2015. Individuals who were age 40 years and older were included in the analysis. The sedative-hypnotic users were defined as individuals prescribed 30 or more defined daily doses of sedative-hypnotics per year since January 2004. Sedative-hypnotics were classified based on type and total amount. We estimated the risk of mortality (death from January 2004 to December 2015) using time-dependent Cox regression model adjusted for age, sex, Charlson Comorbidity Index, and psychiatric comorbidity. Results: We identified 180,823 study participants who used sedative-hypnotics and 320,136 nonusers. In a multivariate model, study participants who used sedative-hypnotics had significantly higher mortality risk than nonusers (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.12-1.16). Specifically, study participants who used zolpidem had a higher mortality risk (HR 1.59, 95% CI 1.52-1.67) than nonusers. Conclusions: Based on the current study results, sedative-hypnotics were associated with an increased risk of mortality, especially in study participants who used zolpidem.