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Original Research

Relationship Between Zolpidem Use and Stroke Risk: A Taiwanese Population-Based Case-Control Study

Wei-Shih Huang, MD; Chon-Haw Tsai, MD, PhD; Che-Chen Lin, MSc; Chih-Hsin Muo, MSc; Fung-Chang Sung, PhD; Yen-Jung Chang, PhD; and Chia-Hung Kao, MD

Published: May 15, 2013

Article Abstract

Objective: To evaluate the relationship between the use of zolpidem and risk of subsequent stroke in Taiwanese patients.

Method: This case-control study used data obtained from the National Health Insurance Research Database to determine whether the use of zolpidem is associated with an increased risk of stroke. The case group comprised 12,747 patients who were newly diagnosed with stroke between January 1, 2005, and December 31, 2009. We also randomly selected a 4-fold greater number of patients without stroke as a control group. Patients with ischemic and hemorrhagic stroke were frequency-matched with controls on sex, age, and year of index date. We measured the effect of zolpidem and determined the adjusted odds ratios (ORs) with 95% confidence intervals (CIs).

Results: We found that exposure to zolpidem was associated with increased risk of ischemic stroke (OR = 1.37; 95% CI, 1.30-1.44). The risk of ischemic stroke increased significantly with increasing exposure to zolpidem; for average exposures of ≤ 70, 71-470, and > 470 mg per year, the ORs were 1.20, 1.41, and 1.50, respectively; the P value for the trend was < .0001. Regardless of whether people presented with a sleep disorder, the risk of stroke was still greatly increased with zolpidem exposure; the adjusted OR was 1.37 without sleep disorder and 1.41 with sleep disorder.

Conclusions: This population-based study positively associated the use of zolpidem with increased risk of ischemic stroke. Our findings warrant further large-scale and in-depth investigations in this area.

J Clin Psychiatry 2013;74(5):e433-e438

Submitted: September 20, 2012; accepted February 11, 2013 (doi:10.4088/JCP.12m08181).

Corresponding author: Chia-Hung Kao, MD, Department of Nuclear Medicine and PET Center, China Medical University Hospital, No. 2, Yuh-Der Rd, Taichung 404, Taiwan (

Volume: 74

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