Skip to main content

Use of Benzodiazepines and Association with Falls in Older People Admitted to Hospital: A Prospective Cohort Study

Drugs & Aging volume 31, pages 299–310 (2014)Cite this article

Abstract

Background

Hypnosedatives are commonly prescribed for anxiety and sleep problems. Changes in pharmacokinetics and pharmacodynamics of benzodiazepines (BZDs) during ageing may increase their potential to cause adverse outcomes.

Objective

This study aimed to investigate the use of BZDs in acute care settings and explore their association with falls.

Methods

A prospective cohort study was undertaken of patients aged over 70 years consecutively admitted to 11 acute care hospitals in Australia. Data were collected using the interRAI Acute Care assessment tool. Falls were recorded prospectively (in hospital) and retrospectively (in the 90 days prior to admission).

Results

Of 1,412 patients, 146 (10.3 %) were taking BZDs at admission and 155 (11.3 %) at discharge. Incidence rates of in-hospital fallers for users and non-users of BZDs were not statistically different [incidence rate ratio 1.03, 95 % confidence interval (CI) 0.58–1.82]. There was also no significant association between benzodiazepine use at admission and history of falls in the previous 90 days compared with non-users. However, patients on diazepam were significantly more likely to have a history of falls than all other benzodiazepine users (70.8 vs. 36.1 %; p = 0.002), particularly when compared with oxazepam users (70.8 vs. 25.0 %; p < 0.001). Adjusting for confounders, use of diazepam at admission was positively associated with a history of falls compared with all other benzodiazepine users (odds ratio 3.0; 95 % CI 1.1–8.5; p = 0.036).

Conclusions

Different BZDs may vary in their propensity to predispose to falls, with diazepam having the strongest association. The selection of particular BZDs for older patients should be carefully evaluated.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

49,54 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1

References

  1. Mugunthan K, McGuire T, Glasziou P. Minimal interventions to decrease long-term use of benzodiazepines in primary care: a systematic review and meta-analysis. Br J Gen Pract. 2011;61(590):e573–8. doi:10.3399/bjgp11X593857.

    PubMed Central  PubMed  Article  Google Scholar 

  2. Fourrier A, Letenneur L, Dartigues JF, Moore N, Begaud B. Benzodiazepine use in an elderly community-dwelling population: characteristics of users and factors associated with subsequent use. Eur J Clin Pharmacol. 2001;57(5):419–25.

    PubMed  Article  CAS  Google Scholar 

  3. Jorm AF, Grayson D, Creasey H, Waite L, Broe GA. Long-term benzodiazepine use by elderly people living in the community. Aust N Z J Public Health. 2000;24(1):7–10.

    PubMed  Article  CAS  Google Scholar 

  4. Tu K, Mamdani MM, Hux JE, Tu JB. Progressive trends in the prevalence of benzodiazepine prescribing in older people in Ontario, Canada. J Am Geriatr Soc. 2001;49(10):1341–5.

    PubMed  Article  CAS  Google Scholar 

  5. Voyer P, Preville M, Cohen D, Berbiche D, Beland SG. The prevalence of benzodiazepine dependence among community-dwelling older adult users in Quebec according to typical and atypical criteria. Can J Aging. 2010;29(2):205–13. doi:10.1017/S0714980810000115.

    PubMed  Article  Google Scholar 

  6. Smith AJ, Tett SE. How do different age groups use benzodiazepines and antidepressants? Analysis of an Australian administrative database, 2003–6. Drugs Aging. 2009;26(2):113–22. doi:10.2165/0002512-200926020-00003.

    PubMed  Article  CAS  Google Scholar 

  7. Bowie MW, Slattum PW. Pharmacodynamics in older adults: a review. Am J Geriatr Pharmacother. 2007;5(3):263–303. doi:10.1016/j.amjopharm.2007.10.001.

    PubMed  Article  CAS  Google Scholar 

  8. Cusack BJ. Pharmacokinetics in older persons. Am J Geriatr Pharmacother. 2004;2(4):274–302.

    PubMed  Article  CAS  Google Scholar 

  9. Hilmer SN, McLachlan AJ, Le Couteur DG. Clinical pharmacology in the geriatric patient. Fundam Clin Pharmacol. 2007;21(3):217–30. doi:10.1111/j.1472-8206.2007.00473.x.

    Google Scholar 

  10. Sera LC, McPherson ML. Pharmacokinetics and pharmacodynamic changes associated with aging and implications for drug therapy. Clin Geriatr Med. 2012;28(2):273–86. doi:10.1016/j.cger.2012.01.007.

    PubMed  Article  Google Scholar 

  11. Hubbard RE, O’Mahony MS, Woodhouse KW. Medication prescribing in frail older people. Eur J Clin Pharmacol. 2013;. doi:10.1007/s00228-012-1387-2.

    PubMed  Google Scholar 

  12. Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev. 2009;41(2):67–76. doi:10.1080/03602530902722679.

    PubMed  Article  CAS  Google Scholar 

  13. Sotaniemi EA, Arranto AJ, Pelkonen O, Pasanen M. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther. 1997;61(3):331–9. doi:10.1016/S0009-9236(97)90166-1.

    PubMed  Article  CAS  Google Scholar 

  14. Hammerlein A, Derendorf H, Lowenthal DT. Pharmacokinetic and pharmacodynamic changes in the elderly: clinical implications. Clin Pharmacokinet. 1998;35(1):49–64.

    PubMed  Article  CAS  Google Scholar 

  15. Naranjo CA, Herrmann N, Mittmann N, Bremner KE. Recent advances in geriatric psychopharmacology. Drugs Aging. 1995;7(3):184–202.

    PubMed  Article  CAS  Google Scholar 

  16. McLean AJ, Le Couteur DG. Aging biology and geriatric clinical pharmacology. Pharmacol Rev. 2004;56(2):163–84. doi:10.1124/pr.56.2.4.

    PubMed  Article  CAS  Google Scholar 

  17. Bloch F, Thibaud M, Dugue B, Breque C, Rigaud AS, Kemoun G. Psychotropic drugs and falls in the elderly people: updated literature review and meta-analysis. J Aging Health. 2011;23(2):329–46. doi:10.1177/0898264310381277.

    PubMed  Article  Google Scholar 

  18. Chang CM, Chen MJ, Tsai CY, Ho LH, Hsieh HL, Chau YL, et al. Medical conditions and medications as risk factors of falls in the inpatient older people: a case–control study. Int J Geriatr Psychiatry. 2011;26(6):602–7. doi:10.1002/gps.2569.

    PubMed  Article  Google Scholar 

  19. Ensrud KE, Blackwell TL, Mangione CM, Bowman PJ, Whooley MA, Bauer DC, et al. Central nervous system-active medications and risk for falls in older women. J Am Geriatr Soc. 2002;50(10):1629–37.

    PubMed  Article  Google Scholar 

  20. Pariente A, Dartigues JF, Benichou J, Letenneur L, Moore N, Fourrier-Reglat A. Benzodiazepines and injurious falls in community dwelling elders. Drugs Aging. 2008;25(1):61–70.

    PubMed  Article  CAS  Google Scholar 

  21. Woolcott JC, Richardson KJ, Wiens MO, Patel B, Marin J, Khan KM, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med. 2009;169(21):1952–60. doi:10.1001/archinternmed.2009.357.

    PubMed  Article  Google Scholar 

  22. Peel NM. Epidemiology of falls in older age. Can J Aging. Epub 15 Mar 2011. doi:10.1017/S071498081000070X.

  23. Nyberg L, Gustafson Y, Janson A, Sandman PO, Eriksson S. Incidence of falls in three different types of geriatric care: a Swedish prospective study. Scand J Soc Med. 1997;25(1):8–13.

    PubMed  CAS  Google Scholar 

  24. Rubenstein LZ, Josephson KR, Robbins AS. Falls in the nursing home. Ann Intern Med. 1994;121(6):442–51.

    PubMed  Article  CAS  Google Scholar 

  25. Oliver D, Daly F, Martin FC, McMurdo ME. Risk factors and risk assessment tools for falls in hospital in-patients: a systematic review. Age Ageing. 2004;33(2):122–30. doi:10.1093/ageing/afh017.

    PubMed  Article  Google Scholar 

  26. van der Velde N, Stricker BH, Pols HA, van der Cammen TJ. Risk of falls after withdrawal of fall-risk-increasing drugs: a prospective cohort study. Br J Clin Pharmacol. 2007;63(2):232–7. doi:10.1111/j.1365-2125.2006.02736.x.

    PubMed Central  PubMed  Article  Google Scholar 

  27. Berdot S, Bertrand M, Dartigues JF, Fourrier A, Tavernier B, Ritchie K, et al. Inappropriate medication use and risk of falls: a prospective study in a large community-dwelling elderly cohort. BMC Geriatr. 2009;9:30. doi:10.1186/1471-2318-9-30.

    PubMed Central  PubMed  Article  Google Scholar 

  28. Ray WA, Thapa PB, Gideon P. Benzodiazepines and the risk of falls in nursing home residents. J Am Geriatr Soc. 2000;48(6):682–5.

    PubMed  CAS  Google Scholar 

  29. Passaro A, Volpato S, Romagnoni F, Manzoli N, Zuliani G, Fellin R. Benzodiazepines with different half-life and falling in a hospitalized population: the GIFA study. Gruppo Italiano di Farmacovigilanza nell’Anziano. J Clin Epidemiol. 2000;53(12):1222–9 pii: S0895435600002547.

    PubMed  Article  CAS  Google Scholar 

  30. Tamblyn R, Abrahamowicz M, du Berger R, McLeod P, Bartlett G. A 5-year prospective assessment of the risk associated with individual benzodiazepines and doses in new elderly users. J Am Geriatr Soc. 2005;53(2):233–41. doi:10.1111/j.1532-5415.2005.53108.x.

    PubMed  Article  Google Scholar 

  31. Herings RM, Stricker BH, de Boer A, Bakker A, Sturmans F. Benzodiazepines and the risk of falling leading to femur fractures: dosage more important than elimination half-life. Arch Intern Med. 1995;155(16):1801–7.

    PubMed  Article  CAS  Google Scholar 

  32. Brand CA, Martin-Khan M, Wright O, Jones RN, Morris JN, Travers CM, et al. Development of quality indicators for monitoring outcomes of frail elderly hospitalised in acute care health settings: study protocol. BMC Health Serv Res. 2011;11:281. doi:10.1186/1472-6963-11-281.

    PubMed Central  PubMed  Article  Google Scholar 

  33. Lakhan P, Jones M, Wilson A, Courtney M, Hirdes J, Gray LC. A prospective cohort study of geriatric syndromes among older medical patients admitted to acute care hospitals. J Am Geriatr Soc. 2011;59(11):2001–8. doi:10.1111/j.1532-5415.2011.03663.x.

    PubMed  Article  Google Scholar 

  34. Travers C, Byrne G, Pachana N, Klein K, Gray L. Prospective observational study of dementia and delirium in the acute hospital setting. Intern Med J. 2013;43(3):262–9. doi:10.1111/j.1445-5994.2012.02962.x.

    PubMed  Article  CAS  Google Scholar 

  35. Gray LC, Berg K, Fries BE, Henrard JC, Hirdes JP, Steel K, et al. Sharing clinical information across care settings: the birth of an integrated assessment system. BMC Health Serv Res. 2009;9:71. doi:10.1186/1472-6963-9-71.

    PubMed Central  PubMed  Article  Google Scholar 

  36. Gray LC, Bernabei R, Berg K, Finne-Soveri H, Fries BE, Hirdes JP, et al. Standardizing assessment of elderly people in acute care: the interRAI Acute Care instrument. J Am Geriatr Soc. 2008;56(3):536–41. doi:10.1111/j.1532-5415.2007.01590.x.

    PubMed  Article  Google Scholar 

  37. Hirdes JP, Ljunggren G, Morris JN, Frijters DH, Finne Soveri H, Gray L, et al. Reliability of the interRAI suite of assessment instruments: a 12-country study of an integrated health information system. BMC Health Serv Res. 2008;8:277. doi:10.1186/1472-6963-8-277.

  38. Gray LC, Arino-Blasco S, Berg K, Bernabei R, Carpenter I, Finne-Soveri H, et al. interRAI Acute Care (AC) Assessment form and user’s manual. Version 9.1. Washington, DC: interRAI; 2010.

  39. Anstey KJ, von Sanden C, Luszcz MA. An 8-year prospective study of the relationship between cognitive performance and falling in very old adults. J Am Geriatr Soc. 2006;54(8):1169–76. doi:10.1111/j.1532-5415.2006.00813.x.

    PubMed  Article  Google Scholar 

  40. Gleason CE, Gangnon RE, Fischer BL, Mahoney JE. Increased risk for falling associated with subtle cognitive impairment: secondary analysis of a randomized clinical trial. Dement Geriatr Cogn Disord. 2009;27(6):557–63. doi:10.1159/000228257.

    PubMed Central  PubMed  Article  Google Scholar 

  41. Barker MJ, Greenwood KM, Jackson M, Crowe SF. Cognitive effects of long-term benzodiazepine use: a meta-analysis. CNS Drugs. 2004;18(1):37–48.

    PubMed  Article  CAS  Google Scholar 

  42. Clegg A, Young JB. Which medications to avoid in people at risk of delirium: a systematic review. Age Ageing. 2011;40(1):23–9. doi:10.1093/ageing/afq140.

    PubMed  Article  Google Scholar 

  43. Peron EP, Gray SL, Hanlon JT. Medication use and functional status decline in older adults: a narrative review. Am J Geriatr Pharmacother. 2011;9(6):378–91. doi:10.1016/j.amjopharm.2011.10.002.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  44. Payne RA, Abel GA, Simpson CR, Maxwell SR. Association between prescribing of cardiovascular and psychotropic medications and hospital admission for falls or fractures. Drugs Aging. 2013;30(4):247–54. doi:10.1007/s40266-013-0058-z.

    PubMed  Article  Google Scholar 

  45. Nurminen J, Puustinen J, Piirtola M, Vahlberg T, Kivela SL. Psychotropic drugs and the risk of fractures in old age: a prospective population-based study. BMC Public Health. 2010;10:396. doi:10.1186/1471-2458-10-396.

    PubMed Central  PubMed  Article  Google Scholar 

  46. Huang AR, Mallet L, Rochefort CM, Eguale T, Buckeridge DL, Tamblyn R. Medication-related falls in the elderly: causative factors and preventive strategies. Drugs Aging. 2012;29(5):359–76. doi:10.2165/11599460-000000000-00000.

    PubMed  Article  CAS  Google Scholar 

  47. Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Arch Intern Med. 2003;163(22):2716–24. doi:10.1001/archinte.163.22.2716.

    PubMed  Article  Google Scholar 

  48. Laroche ML, Charmes JP, Merle L. Potentially inappropriate medications in the elderly: a French consensus panel list. Eur J Clin Pharmacol. 2007;63(8):725–31. doi:10.1007/s00228-007-0324-2.

    PubMed  Article  Google Scholar 

  49. Holt S, Schmiedl S, Thurmann PA. Potentially inappropriate medications in the elderly: the PRISCUS list. Deutsches Arzteblatt Int. 2010;107(31–32):543–51. doi:10.3238/arztebl2010.0543.

    Google Scholar 

  50. Rognstad S, Brekke M, Fetveit A, Spigset O, Wyller TB, Straand J. The Norwegian General Practice (NORGEP) criteria for assessing potentially inappropriate prescriptions to elderly patients: a modified Delphi study. Scand J Prim Health Care. 2009;27(3):153–9. doi:10.1080/02813430902992215.

    PubMed Central  PubMed  Article  Google Scholar 

  51. Rhalimi M, Helou R, Jaecker P. Medication use and increased risk of falls in hospitalized elderly patients: a retrospective, case–control study. Drugs Aging. 2009;26(10):847–52. doi:10.2165/11317610-000000000-00000.

    PubMed  Article  CAS  Google Scholar 

  52. Lichtenstein MJ, Griffin MR, Cornell JE, Malcolm E, Ray WA. Risk factors for hip fractures occurring in the hospital. Am J Epidemiol. 1994;140(9):830–8.

    PubMed  CAS  Google Scholar 

  53. Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: I. Psychotropic drugs. J Am Geriatr Soc. 1999;47(1):30–9.

    PubMed  CAS  Google Scholar 

  54. Lee JS, Kwok T, Leung PC, Woo J. Medical illnesses are more important than medications as risk factors of falls in older community dwellers? A cross-sectional study. Age Ageing. 2006;35(3):246–51. doi:10.1093/ageing/afj056.

    PubMed  Article  Google Scholar 

  55. de Rekeneire N, Visser M, Peila R, Nevitt MC, Cauley JA, Tylavsky FA, et al. Is a fall just a fall: correlates of falling in healthy older persons. The Health, Aging and Body Composition Study. J Am Geriatr Soc. 2003;51(6):841–6.

    PubMed  Article  Google Scholar 

  56. Ebly EM, Hogan DB, Fung TS. Potential adverse outcomes of psychotropic and narcotic drug use in Canadian seniors. J Clin Epidemiol. 1997;50(7):857–63.

    PubMed  Article  CAS  Google Scholar 

  57. Frels C, Williams P, Narayanan S, Gariballa SE. Iatrogenic causes of falls in hospitalised elderly patients: a case–control study. Postgrad Med J. 2002;78(922):487–9.

    PubMed Central  PubMed  Article  CAS  Google Scholar 

  58. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med. 1995;332(12):767–73. doi:10.1056/NEJM199503233321202.

    PubMed  Article  CAS  Google Scholar 

  59. McLachlan AJ, Pont LG. Drug metabolism in older people: a key consideration in achieving optimal outcomes with medicines. J Gerontol A Biol Sci Med Sci. 2012;67(2):175–80. doi:10.1093/gerona/glr118.

    PubMed  Article  CAS  Google Scholar 

  60. Rowland A, Miners JO, Mackenzie PI. The UDP-glucuronosyltransferases: their role in drug metabolism and detoxification. Int J Biochem Cell Biol. 2013;45(6):1121–32. doi:10.1016/j.biocel.2013.02.019.

    PubMed  Article  CAS  Google Scholar 

  61. Peel N. Validating recall of falls by older people. Accid Anal Prev. 2000;32(3):371–2. doi:10.1016/S0001-4575(99)00066-4.

    PubMed  Article  CAS  Google Scholar 

Download references

Acknowledgments

The preparation of this manuscript was funded by the Princess Alexandra Hospital Private Practice Trust Fund Research Support Grants scheme, and MID-FRAIL-HEALTH-F2-2012-278803, PRVOUK P40/faf/2013

Anna Ballokova, Nancye M. Peel, Daniela Fialova, Ian A. Scott, Leonard C. Gray and Ruth E. Hubbard have no conflicts of interest that are directly relevant to the content of this manuscript.

Author information

Affiliations

  1. Department of Geriatrics and Gerontology, 1st Faculty of Medicine, Charles University in Prague, Londýnská 15, 128 08, Prague, Czech Republic

    Anna Ballokova & Daniela Fialova

  2. Centre for Research in Geriatric Medicine, School of Medicine, University of Queensland, Brisbane, QLD, Australia

    Nancye M. Peel, Leonard C. Gray & Ruth E. Hubbard

  3. Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Prague, Czech Republic

    Daniela Fialova

  4. School of Medicine, The University of Queensland, Brisbane, QLD, Australia

    Ian A. Scott

  5. Department of Internal Medicine and Clinical Epidemiology, Princess Alexandra Hospital, Brisbane, QLD, Australia

    Ian A. Scott

Authors
  1. Anna Ballokova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nancye M. Peel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniela Fialova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ian A. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Leonard C. Gray
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ruth E. Hubbard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna Ballokova.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ballokova, A., Peel, N.M., Fialova, D. et al. Use of Benzodiazepines and Association with Falls in Older People Admitted to Hospital: A Prospective Cohort Study. Drugs Aging 31, 299–310 (2014). https://doi.org/10.1007/s40266-014-0159-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-014-0159-3

Keywords

  • Oxazepam
  • Comprehensive Geriatric Assessment
  • Temazepam
  • Acute Care Setting
  • Cognitive Performance Scale