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Long-Term Use of Zolpidem Increases the Risk of Major Injury: A Population-Based Cohort Study

  • Ming-May Lai
    Affiliations
    Department of Family Medicine, China Medical University & Hospital, Taichung, Taiwan
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  • Cheng-Chieh Lin
    Affiliations
    Department of Family Medicine, China Medical University & Hospital, Taichung, Taiwan

    Institute of Health Care Administration, College of Public Health, China Medical University & Hospital, Taichung, Taiwan

    Department of Healthcare Administration, College of Health Science, Asia University, Taichung, Taiwan
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  • Che-Chen Lin
    Affiliations
    Management Office for Health Data, China Medical University & Hospital, Taichung, Taiwan
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  • Chiu-Shong Liu
    Affiliations
    Department of Family Medicine, China Medical University & Hospital, Taichung, Taiwan
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  • Tsai-Chung Li
    Affiliations
    Department of Healthcare Administration, College of Health Science, Asia University, Taichung, Taiwan

    Graduate Institute of Biostatistics & Chinese Medicine Science and Biostatistics Center, China Medical University, Taichung, Taiwan
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  • Chia-Hung Kao
    Correspondence
    Correspondence: Address to Chia-Hung Kao, MD, Graduate Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, No 2, Yuh-Der Rd, Taichung 404, Taiwan.
    Affiliations
    Graduate Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan

    Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
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      Abstract

      Objective

      To estimate the risk of head injury or fracture requiring hospitalization in patients treated with zolpidem.

      Patients and Methods

      We identified 8188 patients 18 years and older who had received a first prescription for zolpidem between January 1, 2000, and December 31, 2009, and compared them with 32,752 age- and sex-matched patients who had not used sedative-hypnotic agents. Both cohorts were followed up for at least 1 year or until hospitalization for head injury or fracture (major injury). Hazard ratios (HRs) and 95% CIs were calculated by comparing the incidence of major injury requiring hospitalization between the zolpidem user and comparison cohorts, including age groups 18 to 54 and 55 years or more, using a Cox proportional hazards regression analysis.

      Results

      The adjusted HR for major injury in zolpidem users was 1.67 (95% CI, 1.19-2.34). The adjusted HR for major injury in zolpidem users in the younger cohort (aged 18-54 years) was 1.70 (95% CI, 1.15-2.51) and in the older cohort (aged ≥55 years) was 1.57 (95% CI, 0.78-3.13). The adjusted HR for major injury in zolpidem users increased when the zolpidem dosage increased (HR, 2.04; 95% CI, 1.32-3.13 for 71-800 mg/y; HR, 4.37; 95% CI, 2.12-9.01 for 801-1600 mg/y; and HR, 4.74; 95% CI, 2.38-9.42 for >1600 mg/y).

      Conclusion

      The long-term use of zolpidem is associated with a significantly greater risk of head injury or fracture requiring hospitalization than in patients who do not use sedative-hypnotic agents (P<.001), particularly in the younger (aged 18-54 years) patients.

      Abbreviations and Acronyms:

      ARI (absolute risk increase), HR (hazard ratio), ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification), NHI (National Health Insurance), NHIRD (National Health Insurance Research Database), NHRI (National Health Research Institute), Z-drugs (zaleplon, zolpidem, and zopiclone)
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