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. 2018 Oct 15;14(10):1669-1677.
doi: 10.5664/jcsm.7370.

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

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

Jae-Won Choi et al. J Clin Sleep Med. .
Free PMC article


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.

Keywords: mortality; sedative-hypnotics; zolpidem.


Figure 1
Figure 1. Flow diagram.
We randomly selected 827,100 participants representing 5% of Korean NHIS beneficiaries between January 2002 and December 2015 who were 40 years of age or older. Among the selected participants, 18,100 were excluded due to death or loss to follow-up before January 2004. Of the remaining sample, 308,041 participants prescribed any sedative-hypnotics before January 2004 were excluded. Finally, a total of 500,959 participants were included for analysis and followed-up for 13 years. Of these, 68,049 participants died during the study period. NHIS = National Health Insurance Service.
Figure 2
Figure 2. Kaplan-Meier survival curves of sedativehypnotics for mortality classified based on sedativehypnotics dose.
Nonexposure = < 30 DDDs, low-dose = 30–179 DDDs, medium-dose = 180–359 DDDs, high-dose = ≥ 360 DDDs. Kaplan–Meier-estimated survival rate and mortality based on sedative-hypnotics dose. The sedative-hypnotics exposure groups had a significantly lower survival rate than the nonexposure group (P < .0001). The survival rate was proportionally lower as doses of sedative-hypnotics increased (P < .0001). DDD = defined daily dose.
Figure 3
Figure 3. Kaplan-Meier survival curves of sedativehypnotics for mortality classified based on type of sedativehypnotics.
Nonexposure = < 30 DDDs, other groups = ≥ 30 DDDs. Kaplan– Meier-estimated survival rate for mortality based on type of sedativehypnotics. The survival rate of the groups prescribed two or more types of sedative-hypnotics was lower than those of the groups prescribed only one type of sedative-hypnotics. The group prescribed all types of study drugs had the lowest survival rate (P < .0001). DDD = defined daily dose.

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