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)To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Mayo Clinic ProceedingsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Epidemiology of insomnia: what we know and what we still need to learn.Sleep Med Rev. 2002; 6: 97-111
- Ten-year trends in the pharmacological treatment of insomnia.Sleep. 1999; 22: 371-375
- Hypnotics' association with mortality or cancer: a matched cohort study.BMJ Open. 2012; 2: e000850
- National Prescription Audit Plus.IMS Health, Fairfield, CT2003
- Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data.Addiction. 2003; 98: 1371-1378
- Zolpidem use and risk of fracture in elderly insomnia patients.J Prev Med Public Health. 2012; 45: 219-226
- Risk of fractures requiring hospitalization after an initial prescription for zolpidem, alprazolam, lorazepam, or diazepam in older adults.J Am Geriatr Soc. 2011; 59: 1883-1890
- Road traffic accident risk related to prescriptions of the hypnotics zopiclone, zolpidem, flunitrazepam and nitrazepam.Sleep Med. 2008; 9: 818-822
- The analysis of depression and subsequent cancer risk in Taiwan.Cancer Epidemiol Biomarkers Prev. 2011; 20: 473-475
- National Trauma Registry Report: Hospitalizations for Major Injury in Canada, 2010–2011.Canadian Institute for Health Information, Ottawa, ON, Canada2013
- Risk factors for falls in community-dwelling older people: a systematic review and meta-analysis.Epidemiology. 2010; 21: 658-668
- Meta-analysis of the impact of 9 medication classes on falls in elderly persons.Arch Intern Med. 2009; 169 ([published correction appears in Arch Intern Med. 2010;170(5):477]): 1952-1960
National Institute for Health and Clinical Excellence. Guidance on the Use of Zaleplon, Zolpidem and Zopiclone for the Short-Term Management of Insomnia. London: National Institute for Health and Clinical Excellence. Technology Appraisal Guidance, TA77. Issued April 2004. http://guidance.nice.org.uk/TA77. Accessed December 28, 2010.
- Long-term use of zopiclone, zolpidem and zaleplon among Danish elderly and the association with sociodemographic factors and use of other drugs.Pharmacoepidemiol Drug Saf. 2011; 20: 378-385
- Long-term prescription of benzodiazepines and non-benzodiazepines.Gesundheitswesen. 2013; 75 ([in German]): 430-437
- Increased risk of hospitalization related to motor vehicle accidents among people taking zolpidem: a case-crossover study.J Epidemiol. 2011; 21: 37-43
- Perceptions of German GPs on benefits and risks of benzodiazepines and Z-drugs.Swiss Med Wkly. 2013; 143: w13745
Article info
Publication history
Published online: March 31, 2014
Footnotes
For editorial comment, see page 579
Grant Support: The work was supported by the study projects (DMR-103-020 and DMR-102-023) in our hospital, Taiwan Ministry of Health and Welfare Clinical Trial and Research Center for Excellence (DOH102-TD-B-111-004), Taiwan Ministry of Health and Welfare Cancer Research Center for Excellence (MOHW103-TD-B-111-03), and International Research-Intensive Centers of Excellence in Taiwan (NSC101-2911-I-002-303).
Identification
Copyright
© 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
