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

Abstract

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.

Hypnotic drug risks of mortality, infection, depression, and cancer: but lack of benefit

“…More recent meta-analyses have indicated that the mortality risk associated with short sleep is minimal compared to that associated with long sleep 167 , 168 . Several recent studies have replicated the CPSI and CPSII estimates that insomnia has little or no association with mortality after control for confounders 169 , 170 , but not all studies agree. Although a hypothesis that short sleep causes obesity has received recent popularity, some fostered by investigators affiliated with hypnotics manufacturers, no controlled trials indicating that hypnotics reduce obesity have been located.…”

Updates in insomnia diagnosis and treatment

“…10 There is also concern that long-term use of z-drugs may increase the risk of cardiovascular events, cancer, and all-cause mortality, but the data thus far have only come from observational trials and findings have been inconsistent. [12][13][14] Antidepressants are a strong treatment alternative especially in patients reporting comorbid mood disorders. Cognitive behavioral therapy as noted above is a more effective long-term solution for insomnia than simply using an antidepressant.…”

“…10 There is also concern that long-term use of z-drugs may increase the risk of cardiovascular events, cancer, and all-cause mortality, but the data thus far have only come from observational trials and findings have been inconsistent. 12–14…”

Is single acupoint Sanyinjiao (SP 6) effective in managing insomnia? A systematic review of randomized controlled trials

“…Some other adverse effects have also been reported: a fourteen-year follow-up study conducted in Taiwan showed that hypnotics increased the risks of oral and breast cancer in insomniacs with a hazard ratio of 1.49 times compared with insomnia patients who did not use hypnotics (14). A study performed in Korea showed that there were some associations between hypnotics and mortality (15). On the other hand, tolerance to hypnotics is another cause reducing their effectiveness for managing insomnia (16).…”