Abstract
Objective
To evaluate the relationship between the use of zolpidem and subsequent cancer risk
in Taiwanese patients.
Methods
We used data from the National Health Insurance system of Taiwan to investigate whether
use of zolpidem was related to cancer risk. For the study cohort, we identified 14,950
patients who had received a first prescription for zolpidem from January 1, 1998,
through December 31, 2000. For each zolpidem user, we selected randomly 4 comparison
patients without a history of using zolpidem who were frequency-matched by sex, age,
and year of the index date. Incidence rates of all cancers and selected site-specific
cancers were measured by the end of 2009, and related hazard ratios (HRs) and 95%
confidence intervals (CIs) of the cancer were measured as well.
Results
The risk of developing any cancer was greater in patients using zolpidem than in nonusers
(HR, 1.68; 95% CI, 1.55-1.82). The stratified analysis showed that the overall HR
for high-dosage zolpidem (≥300 mg/y) was 2.38. The site-specific cancer risk was the
highest for oral cancer (HR, 2.36; 95% CI, 1.57-3.56), followed by kidney cancer,
esophageal cancer, breast cancer, liver cancer, lung cancer, and bladder cancer (HR,
1.60; 95% CI, 1.06-2.41). Men were at higher risk than women.
Conclusion
This population-based study revealed some unexpected findings, suggesting that the
use of zolpidem may be associated with an increased risk of subsequent cancer. Further
large-scale and in-depth investigations in this area are warranted.
Abbreviations and Acronyms:
CI (confidence interval), CIN (cervical intraepithelial neoplasia), CIS (carcinoma in situ), 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)To read this article in full you will need to make a payment
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References
- Morbidity associated with sleep disorders in primary care: a longitudinal cohort study.Prim Care Companion J Clin Psychiatry. 2007; 9: 338-345
- Characteristics of insomnia in the United States: results of the 1991 National Sleep Foundation Survey I.Sleep. 1999; 22: S347-S353
- Epidemiology of insomnia: prevalence, self-help treatments, consultations, and determinants of help-seeking behaviors.Sleep Med. 2006; 7: 123-130
- Epidemiology of insomnia in Korean adults: prevalence and associated factors.J Clin Neurol. 2009; 5: 20-23
- Long-term treatment of insomnia with zolpidem: a multicentre general practitioner study of 107 patients.J Int Med Res. 1991; 19: 271-279
- Update on the safety considerations in the management of insomnia with hypnotics: incorporating modified-release formulations into primary care.Prim Care Companion J Clin Psychiatry. 2007; 9: 25-31
- Safety and tolerance of zolpidem in the treatment of disturbed sleep: a post-marketing surveillance of 16944 cases.Int Clin Psychopharmacol. 1998; 13: 157-167
- Sleep in patients with chronic primary insomnia during long-term zolpidem administration and after its withdrawal.Int Clin Psychopharmacol. 1996; 11: 255-263
- Adverse reactions to zolpidem: case reports and a review of the literature.Prim Care Companion J Clin Psychiatry. 2010; 12 (pii: PCC.09r00849)
- NDA 19-908 Ambien Pharmacology Memos & Exclusivity Summary.(1992:3) (Accessed July 21, 2011)
- Possibility that certain hypnotics might cause cancer in skin.J Sleep Res. 2008; 17: 245-250
- Effect of zolpidem on the sleep arousal response to nocturnal esophageal acid exposure.Clin Gastroenterol Hepatol. 2009; 7: 948-952
- The analysis of depression and subsequent cancer risk in Taiwan.Cancer Epidemiol Biomarkers Prev. 2011; 20: 473-475
- Cancer Statistics Annual Report.(Accessed July 21, 2011)
- Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates.Cancer. 2010; 116: 544-573
- the association between malignancy and end-stage renal disease in Taiwan.Jpn J Clin Oncol. 2011; 41: 752-757
- 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
- The use of benzodiazepines and related drugs amongst older people in Sweden: associated factors and concomitant use of other psychotropics.Int J Geriatr Psychiatry. 2009; 24: 731-738
- Mortality associated with prescription hypnotics.(Accessed July 21, 2011)
- Evidence That New Hypnotics Cause Cancer.(Accessed July 21, 2011)
- Role of human papilloma virus in the oral carcinogenesis: an Indian perspective.J Cancer Res Ther. 2009; 5: 71-77
- Hepatitis C virus-related hepatocellular carcinoma and liver cirrhosis.J BUON. 2011; 16: 277-281
- Human papillomavirus: science and technologies for the elimination of cervical cancer.Expert Opin Pharmacother. 2011; 12: 2189-2204
Article Info
Footnotes
For editorial comment, see page 417
Grant Support: This work was supported by the study projects DMR-100-076 and DMR-100-077 in our hospital, the Taiwan Department of Health Clinical Trial and Research Center and for Excellence grant DOH101-TD-B-111-004 , and the Taiwan Department of Health Cancer Research Center for Excellence grant DOH101-TD-C-111-005 .
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© 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
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Access this article on ScienceDirectLinked Article
- Insomnia, Hypnotic Drug Use, and Patient Well-being: First, Do No HarmMayo Clinic ProceedingsVol. 87Issue 5
- PreviewMost sleep clinicians know the sinking feeling associated with encountering patients who are frantic about their inability to sleep. Such patients have often taken most hypnotics that we have heard of (and some that we haven't) and visited several other practitioners for this problem. They report being fearful that their insomnia is causing problems with daytime functioning and with health. They are often able to quote recent media reports associating “poor sleep” or “sleep disorders” with bad outcomes, including death.
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- PreviewThe valuable cohort contribution by Kao et al1 associating narcotic zolpidem consumption with heightened iatrogenic malignancy risks would be considerably more compelling if accompanied by proposition of a distinct plausible pathophysiologic mechanism. The most favorably received mechanism would define associations between the physiologic effects of zolpidem that are common to other pharmacologic agents and diagnoses that effect similar intermediary stepwise events epidemiologically linked to oncogenesis.
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