Drugs & Aging

, Volume 30, Issue 3, pp 183–192 | Cite as

Benzodiazepine Use among Older Adults with Chronic Obstructive Pulmonary Disease

A Population-Based Cohort Study
  • Nicholas T. VozorisEmail author
  • Hadas D. Fischer
  • Xuesong Wang
  • Geoffrey M. Anderson
  • Chaim M. Bell
  • Andrea S. Gershon
  • Anne L. Stephenson
  • Sudeep S. Gill
  • Paula A. Rochon
Original Research Article



Patients with chronic obstructive pulmonary disease (COPD) may receive benzodiazepines for a variety of reasons, including as treatment for insomnia, as treatment for depression and anxiety, and to help relieve refractory dyspnoea. However, benzodiazepines have been linked to adverse physiological respiratory outcomes in individuals with COPD. The potential adverse respiratory effects of benzodiazepines in COPD may also be heightened in older adults given their altered pharmacokinetics that increase benzodiazepine half-life. There is minimal information on the scope and nature of benzodiazepine use in the older adult COPD population.


The purpose of this study was to describe patterns of benzodiazepine use among older adults with COPD.


A validated algorithm was applied to Ontario healthcare administrative data to identify older adults with COPD. Incident oral benzodiazepine receipt between 1 April 2004 and 31 March 2009, defined as no benzodiazepines dispensed in the year prior to incident prescription, was examined. Regression techniques were used to identify patient characteristics associated with new benzodiazepine use. Descriptive statistics were performed to describe benzodiazepine use among new users. The analysis was stratified by COPD severity defined by COPD exacerbation frequency (less severe COPD: 0 exacerbations in the year prior; more severe COPD: 1 or more exacerbations in the year prior).


Among 111,445 older adults with COPD, 35,311 (31.7 %) received a new benzodiazepine. New benzodiazepine receipt was higher among individuals with more severe COPD (adjusted odds ratio 1.43, 95 % CI 1.38–1.48). Among new benzodiazepine users, there was a relatively high frequency of receipt of long-acting agents (14.6 %), dispensations for greater than 30 days (32.6 %), second dispensations (22.0 % or 30.6 % for occurrence within 120 % or 200 % days of the index prescription, respectively), early refills (11.6 %), and benzodiazepine receipt during COPD exacerbations (9.0 %). Among individuals with more severe COPD, 35.4 % of incident use occurred during a COPD exacerbation.


Almost one-third of older individuals with COPD received a new benzodiazepine, and rates were higher among those with more severe COPD. Important safety and quality of care issues are potentially raised by the degree and pattern of benzodiazepine use in this older and respiratory-vulnerable population.


Chronic Obstructive Pulmonary Disease Chronic Obstructive Pulmonary Disease Patient Severe Chronic Obstructive Pulmonary Disease Chronic Obstructive Pulmonary Disease Exacerbation Ontario Health Insurance Plan 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study was conducted at the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred.

Conflicts of interest and funding

This study was funded by a Team Grant (OTG-88591) from the Canadian Institutes of Health Research Institute of Nutrition, Metabolism and Diabetes. The funder had no role in the study design; in the collection, analysis and interpretation of data; or in the writing of the article and the decision to submit it for publication. All authors are independent from the funders.

Author contributions

All authors had access to all the data presented. Conception and design: N.T.V., H.D.F., G.M.A., C.M.B., A.S.G., A.L.S., S.S.G. and P.A.R.; analysis and interpretation: N.T.V., H.D.F., X.W., G.M.A., C.M.B., A.S.G., A.L.S., S.S.G. and P.A.R.; and drafting the manuscript for important intellectual content: N.T.V., H.D.F., X.W., G.M.A., C.M.B., A.S.G., A.L.S., S.S.G. and P.A.R.


  1. 1.
    Cohn MA, Morris DD, Juan D. Effects of estazolam and flurazepam on cardiopulmonary function in patients with chronic obstructive pulmonary disease. Drug Saf. 1992;7:152–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Jolly E, Aguirre L, Jorge E, et al. Acute effect of lorazepam on respiratory muscles in stable patients with chronic obstructive pulmonary disease. [Article in Spanish]. Medicina (B Aires). 1996;56:472–8.Google Scholar
  3. 3.
    Murciano D, Aubier M, Palacios S, et al. Comparison of zolpidem (Z), triazolam (T), and flunitrazepam (F) effects on arterial blood gases and control of breathing in patients with severe chronic obstructive pulmonary disease (COPD). Chest. 1990;97:51S–2S.PubMedGoogle Scholar
  4. 4.
    Murciano D, Armengaud MH, Cramer PH, et al. Acute effects of zolpidem, triazolam and flunitrazepam on arterial blood gases and control of breathing in severe COPD. Eur Respir J. 1993;6:625–9.PubMedGoogle Scholar
  5. 5.
    Rudolf M, Geddes DM, Turner JA, et al. Depression of central respiratory drive by nitrazepam. Thorax. 1978;33:97–100.PubMedCrossRefGoogle Scholar
  6. 6.
    Block AJ, Dolly FR, Slayton PC. Does flurazepam ingestion affect breathing and oxygenation during sleep in patients with chronic obstructive lung disease? Am Rev Respir Dis. 1984;129:230–3.PubMedGoogle Scholar
  7. 7.
    Beaupré A, Soucy R, Phillips R, et al. Respiratory center output following zopiclone or diazepam administration in patients with pulmonary disease. Respiration. 1988;54:235–40.PubMedCrossRefGoogle Scholar
  8. 8.
    Berry RB, McCasland CR, Light RW. The effect of triazolam on the arousal response to airway occlusion during sleep in normal subjects. Am J Respir Crit Care Med. 1992;146:1256–560.CrossRefGoogle Scholar
  9. 9.
    Celli BR, ATS/ERS Task Force. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004;23:932–46.PubMedCrossRefGoogle Scholar
  10. 10.
    Greenblatt DJ, Shader RI, Harmatz JS. Implications of altered drug disposition in the elderly: studies of benzodiazepines. J Clin Pharmacol. 1989;29:866–72.PubMedCrossRefGoogle Scholar
  11. 11.
    Greenblatt DJ, Harmatz JS, Shader RI. Clinical pharmacokinetics of anxiolytics and hypnotics in the elderly. Therapeutic considerations (Part I). Clin Pharmacokinet. 1991;21:165–77.PubMedCrossRefGoogle Scholar
  12. 12.
    Tamblyn RM, McLeod PJ, Abrahamowicz M, et al. Questionable prescribing for elderly patients in Quebec. CMAJ. 1994;150:1801–9.PubMedGoogle Scholar
  13. 13.
    Tu K, Mamdani MM, Hux JE, et al. Progressive trends in the prevalence of benzodiazepine in older people in Ontario, Canada. J Am Geriatr Soc. 2001;49:1341–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Busto UE, Sproule BA, Knight K, et al. Use of prescription and nonprescription hypnotics in a Canadian elderly population. Can J Clin Pharmacol. 2001;8:213–21.PubMedGoogle Scholar
  15. 15.
    Hogan DB, Maxwell CJ, Fung TS. Prevalence and potential consequences of benzodiazepine use in senior citizens: results from the Canadian Study of Aging and Health. Can J Clin Pharmacol. 2003;10:72–7.PubMedGoogle Scholar
  16. 16.
    Halme AS, Beland SG, Preville M, Tannenbaum C. Uncovering the source of new benzodiazepine prescriptions in community-dwelling older adults. Int J Geriatr Psychiatry. 2012. doi: 10.1002/gps.3818.PubMedGoogle Scholar
  17. 17.
    Simon GE, VonKorff M, Barlow W, et al. Predictors of chronic benzodiazepine use in a health maintenance organization sample. J Clin Epidemiol. 1996;49:1067–73.PubMedCrossRefGoogle Scholar
  18. 18.
    Magrini N, Vaccheri A, Parma E, et al. Use of benzodiazepines in the Italian general population: prevalence, pattern of use and risk factors for use. Eur J Clin Pharmacol. 1996;50:19–25.PubMedCrossRefGoogle Scholar
  19. 19.
    Kirby M, Denihan A, Bruce I, et al. Benzodiazepine use among the elderly in the community. Int J Geriatr Psychiatry. 1999;14:280–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Gleason PP, Schulz R, Smith NL, et al. Correlates and prevalence of benzodiazepine use in community-dwelling elderly. J Gen Intern Med. 1998;13:243–50.PubMedCrossRefGoogle Scholar
  21. 21.
    Fourrier A, Letenneur L, Dartigues JF, et al. Benzodiazepine use in an elderly community-dwelling population. Characteristics of users and factors associated with subsequent use. Eur J Clin Pharmacol. 2001;57:419–25.PubMedCrossRefGoogle Scholar
  22. 22.
    Ohayon MM, Lader MH. Use of psychotropic medication in the general population of France, Germany, Italy, and the United Kingdom. J Clin Psychaitry. 2002;63:817–25.CrossRefGoogle Scholar
  23. 23.
    Cormick W, Olson LG, Hensley MJ, et al. Nocturnal hypoxaemia and quality of sleep in patients with chronic obstructive lung disease. Thorax. 1986;41:846–54.PubMedCrossRefGoogle Scholar
  24. 24.
    Klink ME, Quan SF. Prevalence of reported sleep disturbances in a general adult population and their relationship to obstructive airways diseases. Chest. 1987;91:540–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Klink ME, Dodge R, Quan SF. The relation of sleep complaints to respiratory symptoms in a general population. Chest. 1994;105:151–4.PubMedCrossRefGoogle Scholar
  26. 26.
    Hill K, Geist R, Goldstein RS, et al. Anxiety and depression in end-stage COPD. Eur Resp J. 2008;31:667–77.CrossRefGoogle Scholar
  27. 27.
    Maurer J, Rebbapragada V, Borson S, et al. Anxiety and depression in COPD: current understanding, unanswered questions and research needs. Chest. 2008;134:43S–56S.PubMedCrossRefGoogle Scholar
  28. 28.
    Marciniuk D, Goodridge D, Hernandez P, Canadian Thoracic Society COPD Committee Dyspnea Expert Working Group, et al. Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: a Canadian Thoracic Society clinical practice guideline. Can Respir J. 2011;18:69–78.PubMedGoogle Scholar
  29. 29.
    Gershon AS, Wang C, Guan J, et al. Identifying individuals with physician diagnosed COPD in health administrative databases. J COPD. 2009;6:388–94.CrossRefGoogle Scholar
  30. 30.
    Levy R, O’Brien BJ, Sellors C, et al. Coding accuracy of administrative drug claims in the Ontario Drug Benefit database. Can J Pharmacol. 2003;10:67–71.Google Scholar
  31. 31.
    Donaldson GC, Seemungal TA, Bhowmik A, et al. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002;57:847–52.PubMedCrossRefGoogle Scholar
  32. 32.
    Hurst JR, Vestbo J, Anzueto A, et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010;363:1128–38.PubMedCrossRefGoogle Scholar
  33. 33.
    Connors AF Jr, Dawson NV, Thomas C, et al. Outcomes following acute exacerbation of severe chronic obstructive lung disease. The SUPPORT investigators (Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments). Am J Respir Crit Care Med. 1996;154:959–67.PubMedCrossRefGoogle Scholar
  34. 34.
    Miravitlles M, Guerrero T, Mayordomo C, et al. Factors associated with increased risk of exacerbation and hospital admission in a cohort of ambulatory COPD patients: a multiple logistic regression analysis. The EOLO Study Group. Respiration. 2000;67:495–501.PubMedCrossRefGoogle Scholar
  35. 35.
    O’Donnell DE, Hernandez P, Kaplan A, et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease—2008 update: highlights for primary care. Can Resp J. 2008;15S:1A–8A.Google Scholar
  36. 36.
    Canadian Pharmacists Association. Compendium of pharmaceuticals and specialties. Ottawa: The Canadian Drug Reference for Health Professionals. Canadian Pharmacists Association; 2008.Google Scholar
  37. 37.
    Rochon PA, Normand SL, Gomes T, et al. Antipsychotic therapy and short-term serious events in older adults with dementia. Arch Inter Med. 2008;168:1090–6.CrossRefGoogle Scholar
  38. 38.
    Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2011.
  39. 39.
    Vozoris NT, Leung RS. Sedative medication use: prevalence, risk factors, and associations with body mass index using population-level data. Sleep. 2011;34:869–74.PubMedGoogle Scholar
  40. 40.
    Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Int Med. 2009;169:1952–60.CrossRefGoogle Scholar
  41. 41.
    Glass J, Lanctôt KL, Herrmann N, et al. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005;331:1169–76.PubMedCrossRefGoogle Scholar
  42. 42.
    Barbone F, McMahon AD, Davey PG, et al. Association of road-traffic accidents with benzodiazepine use. Lancet. 1998;352:1331–6.PubMedCrossRefGoogle Scholar
  43. 43.
    The American Geriatrics Society 2012 Beers Criteria Expert Panel. American Geriatrics Society updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60:616–31.Google Scholar
  44. 44.
    Hemmelgarn B, Suissa S, Huang A, et al. Benzodiazepine use and the risk of motor vehicle crash in the elderly. JAMA. 1997;278:27–31.PubMedCrossRefGoogle Scholar
  45. 45.
    Ray WA, Griffin MR, Downey W. Benzodiazepines of long and short elimination half-life and the risk of hip fracture. JAMA. 1989;262:3303–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Bell CM, Fischer HD, Gill SS, et al. Initiation of benzodiazepines in the elderly after hospitalization. J Gen Intern Med. 2007;22:1024–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Nicholas T. Vozoris
    • 1
    • 3
    • 7
    Email author
  • Hadas D. Fischer
    • 2
  • Xuesong Wang
    • 2
  • Geoffrey M. Anderson
    • 2
    • 4
    • 5
  • Chaim M. Bell
    • 2
    • 3
    • 4
    • 8
  • Andrea S. Gershon
    • 2
    • 3
  • Anne L. Stephenson
    • 1
    • 3
    • 6
  • Sudeep S. Gill
    • 2
    • 7
  • Paula A. Rochon
    • 2
    • 3
    • 4
    • 5
  1. 1.Division of Respirology, Department of MedicineSt. Michael’s HospitalTorontoCanada
  2. 2.Institute for Clinical and Evaluative SciencesTorontoCanada
  3. 3.Department of MedicineUniversity of TorontoTorontoCanada
  4. 4.Institute of Health Policy, Management, and EvaluationUniversity of TorontoTorontoCanada
  5. 5.Women’s College Research InstituteWomen’s College HospitalTorontoCanada
  6. 6.Department of Medicine and Keenan Research Centre in the Li Ka Shing Knowledge InstituteSt. Michael’s HospitalTorontoCanada
  7. 7.Department of Medicine Queen’s UniversityKingstonCanada
  8. 8.Division of Internal Medicine, Department of MedicineMount Sinai HospitalTorontoCanada

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