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Effect of Concomitant Use of Benzodiazepines and Other Drugs on the Risk of Injury in a Veterans Population

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Abstract

Background: Benzodiazepines comprise a class of drugs that when used as monotherapy are generally acknowledged to pose a risk for injury by increasing the likelihood of falls, fall-related injuries, adverse drug events and car accidents. Benzodiazepines may also be used concomitantly with other high risk medications that may further exacerbate the risk of injury. The aim of this study is to examine the occurrence of the concomitant use of benzodiazepines and other drugs and then quantify the indirect effect of these drug combinations on the likelihood of an injury-related healthcare episode.

Methods: A multivariate model was specified that included outpatient prescription data and inpatient/outpatient medical utilisation records for 13 745 patients at a Veterans Administration hospital system over a 3-year period (1999–2001). We analysed 133 872 outpatient benzodiazepine prescriptions and >1.5 million non-benzodiazepine prescriptions for the study population. Micromedex software was used to identify combinations of benzodiazepines and other drugs that are likely to result in ‘major’ interactions. We then further restricted our focus to the use of these drug combinations within a 30-day period prior to an injury-related medical event. The adjusted odds ratio on a variable characterising concomitant use of a benzodiazepine and another drug within this period was used to quantify the relative risk of injury. The principal outcome was the estimated risk of an injury-related healthcare episode within a 30-day period when taking both a benzodiazepine and another drug with a ‘major’ severity rating as defined by Micromedex. The risk of injury was adjusted for comorbidities, hospital discharges, marital status, age, mean arterial pressure and body mass index, as well as the dose of benzodiazepine (converted to diazepam equivalents) and duration of benzodiazepine treatment.

Results: Of the 1110 unique individuals who experienced an injury, 790 (71.2%) patients had used a benzodiazepine in combination with another drug. Furthermore, only 4.3% (320/7522) of the patients taking benzodiazepines who did not have concomitant drug use experienced an injury. The occurrence of this concomitant use increased the odds of an injury >2-fold in the model. Dose and duration of benzodiazepine use, as well as certain comorbidities, were also associated with an increased risk for injury, whereas being married reduced the risk.

Conclusions: This is the first large-scale study to quantify the impact of concomitant use of benzodiazepines and other drugs on the risk of injury in a population of Veterans Administration patients. It demonstrates the utility of expanding the focus of inappropriate medication usage to include analyses that link potentially inappropriate drug use with healthcare utilisation for injuries.

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References

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

    Article  PubMed  CAS  Google Scholar 

  2. Kohn LT, Corrigan JM, Donaldson MS, editors. To err is human: building a safer health system committee on quality of health care in America. Washington, DC: Institute of Medicine, 2000

    Google Scholar 

  3. Castle SC. High risk medications and falls: a practical approach to risk management. Presented at the 3rd Annual Evidence-Falls Conference; 2002 Mar 5; Tampa (FL): VA Patient Safety Center, 2002

    Google Scholar 

  4. Smith RG. Fall-contributing adverse effects of the most frequently prescribed drugs. J Am Podiatr Med Assoc 2003; 93: 42–50

    PubMed  Google Scholar 

  5. Morrissey EFR, McElnay JC, Scott M, et al. Influence of drugs, demographics and medical history on hospital readmission of elderly patients: a predictive model. Clin Drug Invest 2003; 23: 119–28

    Article  Google Scholar 

  6. Evans JG. Drugs and falls in later life [letter]. Lancet 2003; 361: 448

    Article  PubMed  Google Scholar 

  7. Rizzo JA, Friedkin R, Williams CS, et al. Health care utilization and costs in a Medicare population by fall status. Med Care 1998; 36: 1174–88

    Article  PubMed  CAS  Google Scholar 

  8. Fick DM, Waller JL, Maclean JR, et al. Potentially inappropriate medication use in a medicare managed care population: association with higher costs and utilization. J Manag Care Pharm 2001; 7: 407–13

    Google Scholar 

  9. Neutel CI. Risk of traffic accident injury after a prescription for a benzodiazepine. Ann Epidemiol 1995; 5: 239–44

    Article  PubMed  CAS  Google Scholar 

  10. Barbone F, McMahon AD, Davey PG, et al. Association of road-traffic accidents with benzodiazepine use. Lancet 1998; 24: 1331–6

    Article  Google Scholar 

  11. Oster G, Huse DM, Adams SF, et al. Benzodiazepine tranquilizers and the risk of accidental injury. Am J Public Health 1990; 80: 1467–70

    Article  PubMed  CAS  Google Scholar 

  12. Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis. Part I and part II. J Am Geriatr Soc 1999; 47: 30–50

    PubMed  CAS  Google Scholar 

  13. Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly: an update. Arch Intern Med 1997; 157: 1531–6

    Article  PubMed  CAS  Google Scholar 

  14. Weiner DK, Hanlon JT, Studenski SA. Effects of central nervous system polypharmacy on falls liability in community dwelling elderly. Gerontology 1998; 44: 217–21

    Article  PubMed  CAS  Google Scholar 

  15. Schwab M, Roder F, Aleker T, et al. Psychotropic drug use, falls and hip fracture in the elderly. Aging (Milano) 2000; 12: 234–9

    CAS  Google Scholar 

  16. Liu GG, Christensen DB. The continuing challenge of inappropriate prescribing in the elderly: an update of the evidence. J Am Pharm Assoc 2002; 42: 847–57

    Article  Google Scholar 

  17. Zhan C, Sangl J, Bierman AS, et al. Potentially inappropriate medication use in the community-dwelling elderly: findings from the 1996 Medical Expenditures Panel Survey. JAMA 2001; 286: 2823–9

    Article  PubMed  CAS  Google Scholar 

  18. Hanlon JT, Fillenbaum G, Kuchibhatla M, et al. Inappropriate drug use, functional status decline, and mortality among community dwelling elderly [letter]. Gerontologist 2000; 40: 37

    Google Scholar 

  19. Gandhi TK, Weingart SN, Borus J, et al. Adverse drug events in ambulatory care. N Engl J Med 2003; 348: 1556–64

    Article  PubMed  Google Scholar 

  20. Tinetti ME, Liu WL, Claus EB. Predictors and prognosis of inability to get up after falls among elderly persons. JAMA 1993; 269: 65–70

    Article  PubMed  CAS  Google Scholar 

  21. Cumming RG. Epidemiology of medication-related falls and fractures in the elderly. Drugs Aging 1998; 12: 43–53

    Article  PubMed  CAS  Google Scholar 

  22. Koski K, Luukinen H, Laippala P, et al. Physiological factors and medications as predictors of injurious falls by elderly people: a prospective population-based study. Age Ageing 1996; 25: 29–38

    Article  PubMed  CAS  Google Scholar 

  23. Neutel CI, Hirdes JP, Maxwell CJ, et al. New evidence on benzodiazepine use and falls: the time factor. Age Ageing 1996; 25: 273–8

    Article  PubMed  CAS  Google Scholar 

  24. Grad R, Tamblyn R, Holbrook AM, et al. Risk of a new benzodiazepine prescription in relation to recent hospitalization. J Am Geriatr Soc 1999; 47: 184–8

    PubMed  CAS  Google Scholar 

  25. French DD, Campbell R, Spehar A, et al. Benzodiazepines and injury: a risk adjusted model. Pharmacoepidemiol Drug Saf. Epub 2004 Apr 23 2005; 14: 17–24

    Article  Google Scholar 

  26. Tillement JP, Albengres E, Cottin D, et al. The risk of falling due to benzodiazepine administration, alone or in combination, in elderly subjects. Therapie 2001; 56: 435–40

    Article  PubMed  CAS  Google Scholar 

  27. Thomson MICROMEDEX® Health Series 1974-2004 Vol. 119 [online]. Available from URL: http://www.micromedex.com [accessed 2005 Oct 12]

  28. Megarbane B, Gueye P, Baud F. Interactions between benzodiazepines and opioids. Ann Med Interne (Paris) 2003; 154: S64–72

    Google Scholar 

  29. Maurer PM, Bartkowski RR. Drug interactions of clinical significance with opioid analgesics. Drug Saf 1993; 8: 30–48

    Article  PubMed  CAS  Google Scholar 

  30. Moreno MR, Rojas CO, Gilbert-Rahola J, et al. Drug interactions of methadone with CNS-active agents. Actas Esp Psiquiatr 1999; 27: 103–10

    Google Scholar 

  31. Aston H. Guidelines for the rational use of benzodiazepines: when and what to use. Drugs 1994; 48: 25–38

    Article  Google Scholar 

  32. Jenice GS, Sohn L, Harada ND. Living alone and outpatient care use by older veterans. J Am Geriatr Soc 2004; 52: 617–22

    Article  Google Scholar 

  33. Tinetti ME, McAvay G, Claus E. Does multiple risk factor reduction explain the reduction in fall rate in the Yale FICSIT trial? Frailty and injuries cooperative studies of intervention techniques. Am J Epidemiol 1996; 144: 389–99

    Article  PubMed  CAS  Google Scholar 

  34. Wei TS, Hu CH, Wang SH, et al. Fall characteristics, functional mobility and bone mineral density as risk factors of hip fracture in the community-dwelling ambulatory elderly. Osteoporos Int 2001; 12: 1050–5

    Article  PubMed  CAS  Google Scholar 

  35. Pope GC. Diagnostic cost group hierarchical condition category models for medicare risk adjustment. Final Report to the US Health Care Financing Administration under Contract No. 500-95-048. Waltham (MA): Health Economics Research Inc., 2000 Dec

    Google Scholar 

  36. Elixhauser A, Steiner C, Harris DR, et al. Comorbidity measures for use with administrative data. Med Care 1998; 36: 8–27

    Article  PubMed  CAS  Google Scholar 

  37. Johnston JA, Wagner DP, Timmons S, et al. Impact of different measures of comorbid disease on predicted mortality of intensive care unit patients. Med Care 2002; 40: 929–40

    Article  PubMed  Google Scholar 

  38. Stukenborg GJ, Wagner DP, Connors AF. Comparison of the performance of two comorbidity measures, with and without information from prior hospitalizations. Med Care 2001; 39: 727–39

    Article  PubMed  CAS  Google Scholar 

  39. Fick DM, Cooper JW, Wade WE, et al. Updating the Beers criteria for potentially inappropriate medication use in older adults. Arch Intern Med 2003; 163: 2716–24

    Article  PubMed  Google Scholar 

  40. SAS Language: reference, version 8. Cary (NC): SAS Institute, 2001

  41. Eto F, Saotome I, Furuichi T, et al. Effects of long-term use of benzodiazepine on gait and standing balance in the elderly. Ann N Y Acad Sci 1998; 860: 543–5

    Article  PubMed  CAS  Google Scholar 

  42. Abarca J, Malone DC, Armstrong EP, et al. Concordance of severity ratings provided in four drug interaction compendia. J Am Pharm Assoc 2004; 128: 131–4

    Google Scholar 

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Acknowledgements

The research reported here was supported by the Department of Veterans Affairs, Veterans Health Administration (VHA), VISN-8. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. VISN-8 Measurement and Evaluation Team, James A. Haley Hospital, 13000 Bruce B. Downs Boulevard (118M), Tampa, Florida, 33612, USA

    Dustin D. French

  2. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

    Thomas N. Chirikos

  3. Suncoast Center for Patient Safety, University of South Florida, Tampa, Florida, USA

    Andrea Spehar

  4. VISN-8 Patient Safety Center, James A. Haley Hospital, Tampa, Florida, USA

    Andrea Spehar, Robert Campbell & Tatjana Bulat

  5. VISN-8 Pharmacy Benefit Management, James A. Haley Hospital, Tampa, Florida, USA

    Heidi Means

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  1. Dustin D. French
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  2. Thomas N. Chirikos
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  3. Andrea Spehar
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  4. Robert Campbell
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  5. Heidi Means
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  6. Tatjana Bulat
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Correspondence to Dustin D. French.

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French, D.D., Chirikos, T.N., Spehar, A. et al. Effect of Concomitant Use of Benzodiazepines and Other Drugs on the Risk of Injury in a Veterans Population. Drug-Safety 28, 1141–1150 (2005). https://doi.org/10.2165/00002018-200528120-00008

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