Association of Hypnotics With Stroke Risk: A Population-Based Case-Control Study

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Background: The aim of this study was to determine what association, if any, hypnotics have on the risk of stroke events.

Method: In a nationwide population-based case-control study, cases were patients with incident stroke diagnosed between January 1, 2006, and December 31, 2006. Patients with hemorrhagic or ischemic stroke diagnosis codes (ICD-9-CM codes 430–438) and who had been hospitalized for further treatment were included in the study. Patients with any type of stroke diagnosed before 2006 were excluded. The authors selected 2,779 stroke patients and 27,790 controls matched for age, gender, physician visit date, and comorbidities. The impact of hypnotics on stroke was examined by multiple logistic regression models and sensitivity analyses.

Results: Individuals prescribed any hypnotic had elevated risk of stroke compared to those prescribed no hypnotics. For groups prescribed 1–27, 28–148, and ≥ 149 pills, odds ratios for stroke were 1.71 (95% CI, 1.49–1.96), 1.84 (95% CI, 1.62–2.11), and 1.45 (95% CI, 1.26–1.68), respectively. Adjusted odds ratios were elevated in separate analyses for zolpidem and estazolam. The observed results were robust with stratification by comorbidities, such as hypertension and diabetes, and using ischemic stroke as the case group.

Conclusions: This study shows that, in a case-control study matched for age, gender, and comorbidities using multiple logistic regression and sensitivity tests, zolpidem and estazolam were slightly associated with an increased risk of stroke. Further large-scale and in-depth studies should be performed. Use of hypnotics should always be determined by specialists, and adverse effects should be continuously monitored.

Prim Care Companion CNS Disord 2014;16(2):doi:10.4088/PCC.13m01583