Advertisement

Current Epidemiology Reports

, Volume 6, Issue 3, pp 390–401 | Cite as

Mixed Bag “Polypharmacy”: Methodological Pitfalls and Challenges of This Exposure Definition

  • Caroline SiroisEmail author
  • Marc Simard
  • Emmanuelle Gosselin
  • Marie-Eve Gagnon
  • Barbara Roux
  • Marie-Laure Laroche
Pharmacoepidemiology (U Haug, Section Editor)
  • 18 Downloads
Part of the following topical collections:
  1. Topical Collection on Pharmacoepidemiology

Abstract

Purpose of Review

The use of multiple medications is common in older adults but is associated with negative health outcomes. However, polypharmacy is not uniformly defined, and there is scant data on how the variety of definitions and their limitations hinder the development of sound scientific knowledge. The article intends to illustrate the challenges of this exposure definition.

Recent Findings

The array of thresholds for defining polypharmacy renders comparisons between results difficult. Few studies take into account the fact that polypharmacy is a changing exposure over time. In addition, although studies tend to recognize the confounding effect of multimorbidity, residual bias remains a concern.

Summary

Current studies in polypharmacy often ignore basic epidemiological principles for defining exposure. Future research should integrate time-varying exposure and methods to better control confounding bias. This will help determine the positive/negative impacts of polypharmacy and help establish if polypharmacy conveys information beyond being a marker of health status.

Keywords

Pharmacoepidemiology Polypharmacy Definition Exposure Methodology 

Notes

Compliance with Ethical Standards

Conflict of Interest

Caroline Sirois reports grants from the Fonds de recherche du Québec-Santé and from the Centre de recherche sur les soins et les services de première ligne de l’Université Laval. Marie-Eve Gagnon receives a scholarship from the Fonds de recherche du Québec-Santé. Marc Simard, Emmanuelle Gosselin, Barbara Roux, and Marie-Laure Laroche declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Guharoy R. Polypharmacy: America’s other drug problem. Am J Health Syst Pharm. 2017;74(17):1305–6.Google Scholar
  2. 2.
    Kantor ED, Rehm CD, Haas JS, Chan AT, Giovannucci EL. Trends in prescription drug use among adults in the United States from 1999-2012. JAMA. 2015;314(17):1818–31.Google Scholar
  3. 3.
    Moriarty F, Hardy C, Bennett K, Smith SM, Fahey T. Trends and interaction of polypharmacy and potentially inappropriate prescribing in primary care over 15 years in Ireland: a repeated cross-sectional study. BMJ Open. 2015;5(9):e008656.Google Scholar
  4. 4.
    Canadian Institute for Health Information. Drug use among seniors in Canada, 2016. Ottawa, ON: CIHI; 2018.Google Scholar
  5. 5.
    Pedros C, Formiga F, Corbella X, Arnau JM. Adverse drug reactions leading to urgent hospital admission in an elderly population: prevalence and main features. Eur J Clin Pharmacol. 2016;72(2):219–26.Google Scholar
  6. 6.
    Johnell K, Klarin I. The relationship between number of drugs and potential drug-drug interactions in the elderly. Drug Saf. 2007;30(10):911–8.Google Scholar
  7. 7.
    Drumbeck S, Flynn A, Nairn M, Wilson M, Trewwek S, Mercer SW, et al. Drug-disease and drug-drug interactions: systematic examination of recommendations in 12 UK national clinical guidelines. BMJ. 2015;350:h949.Google Scholar
  8. 8.
    Blanco-Reina E, Garcia-Merino MR, Ocana-Riola R, Aguilar-Cano L, Valdllos J, Belldo-Estevez I, et al. Assessing potentially inappropriate prescribing in community-dwelling older patients using the updated version of STOPP-START criteria: a comparison of profiles and prevalences with respect to the original version. PLoS One. 2016;11(12):e0167586.Google Scholar
  9. 9.
    Payne RA, Abel GA, Avery AJ, Mercer SW, Roland MO. Is polypharmacy always hazardous? A retrospective cohort analysis using linked electronic health records from primary and secondary care. Br J Clin Pharmacol. 2014;77(6):1073–82.Google Scholar
  10. 10.
    Fried TR, O’Leary J, Towle V, Goldstein MK, Trentalange M, Martin DK. Health outcomes associated with polypharmacy in community-dwelling older adults: a systematic review. J Am Geriatr Soc. 2014;62(12):2261–72.Google Scholar
  11. 11.
    Gutierrez-Valencia M, Izquierdo M, Cesari M, Casas-Herrero A, Inzitari M, Martinez-Velilla N. The relationship between frailty and polypharmacy in older people: a systematic review. Br J Clin Pharmacol. 2018;84(7):1432–44.Google Scholar
  12. 12.
    • Sirois C, Domingues NS, Laroche ML, Zongo A, Lunghi C, Guénette L, et al.Polypharmacy definitions for multimorbid older adults need stronger foundations to guide research, clinical practice and public health: results of a scoping review. Comprehensive review of polypharmacy definitions. Google Scholar
  13. 13.
    • Masnoon N, Shakib S, Kalisch-Ellett L, Caughey GE. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17(1):230 Comprehensive review of polypharmacy definitions. Google Scholar
  14. 14.
    Hand BN, Krause JS, Simpson KN. Polypharmacy and adverse drug events among propensity score matched privately insured persons with and without spinal cord injury. Spinal Cord. 2018;56:591–7.Google Scholar
  15. 15.
    Wang R, Chen L, Fan L, Gao D, Liang Z, He J, et al. Incidence and effects of polypharmacy on clinical outcome among patients aged 80+: a five-year follow-up study. PLoS One. 2015;10(11):e014123.Google Scholar
  16. 16.
    Projetti M, Raparelli V, Olshansky B, Lip GY. Polypharmacy and major adverse events in atrial fibrillation: observations from the AFFIRM trial. Clin Res Cardiol. 2016;105(5):412–20.Google Scholar
  17. 17.
    Khezrian M, McNeil CJ, Myint PK, Murray AD. The association between polypharmacy and late life deficits in cognitive, physical and emotional capability: a cohort study. Int J Clin Parm. 2019;41:251–7.Google Scholar
  18. 18.
    Bennett A, Gnjidic D, Gillett M, Carroll P, Matthews S, Johnell K et al Prevalence and impact of fall-risk-increasing drugs, polypharmacy, and drug–drug Interactions in robust versus frail hospitalised falls patients: A prospective cohort study.Google Scholar
  19. 19.
    Maggiore RJ, Dale W, Gross CP, Feng T, Tew WP, Mohile SG, et al. Polypharmacy and potentially inappropriate medication use among older adults with cancer undergoing chemotherapy: impact on chemotherapy-related toxicity and hospitalization during treatment. J Am Geriatr Soc. 2014;62(8):1505–12.Google Scholar
  20. 20.
    Piccini JP, Hellkamps AS, Washam JB, Becker RC, Breithardt G, Berkowitz SD, et al. Polypharmacy and the efficacy and safety of rivaroxaban versus warfarin in the prevention of stroke in patients with nonvalvular atrial fibrillation. Circulation. 2016;133(4):352–60.Google Scholar
  21. 21.
    Langeard A, Pothier K, Morello R, Lelong-Boulouard V, Lescure P, Bocca ML. Polypharmacy cut-off for gait and cognitive impairments. Front Pharmacol. 2016;7:296.Google Scholar
  22. 22.
    Wimmer BC, Bell JS, Fastbom J, Wiese MD, Johnell K. Medication regimen complexity and polypharmacy as factors associated with all-cause mortality in older people: a population-based cohort study. Ann Parmacother. 2016;50(2):89–95.Google Scholar
  23. 23.
    Harstedt M, Rogmark C, Sutton R, Melander O, Fedorowski A. Polypharmacy and adverse outcomes after hip fracture surgery. J Orthop Surg Res. 2016;11(1):151.Google Scholar
  24. 24.
    Kim TW, Walley AY, Ventura AS, Patts GJ, Heeren TC, Lerner GB, et al. Polypharmacy and the risk of falls and fractures for patients with HIV infection and substance dependence. AIDS Care. 2018;30(2):150–9.Google Scholar
  25. 25.
    Moulis F, Moulis G, Balardy L, Gérard S, Sourdet S, Rougé-Bugat ME, et al. Searching for a polypharmacy threshold associated with frailty. J Am Med Dir Assoc. 2015;16(3):259–61.Google Scholar
  26. 26.
    Yuki A, Otsuka R, Tange C, Nishita Y, Tomida M, Ando F, et al. Polypharmacy is associated with frailty in Japanese community-dwelling older adults. Geriatr Gerontol Int. 2018;18:1497–500.Google Scholar
  27. 27.
    Turner JP, Jamsen KM, Shakib S, Singhal N, Prowse R, Bell JS. Polypharmacy cut-points in older people with cancer: how many medications are too many? Support Care Cancer. 2016;24(4):1831–40.Google Scholar
  28. 28.
    Kim TW, Walley AY, Heeren TC, Patts GJ, Ventura AS, Lerner GB, et al. Polypharmacy and risk of non-fatal overdose for patients with HIV infection and substance dependence. J Subst Abus Treat. 2017;81:1–10.Google Scholar
  29. 29.
    Ahmed B, Nanji K, Mujeeb R, Patel MJ. Effects of polypharmacy on adverse drug reactions among geriatric outpatients at a tertiary care hospital in Karachi: a prospective cohort study. PLoS One. 2014;9(11):e112133.Google Scholar
  30. 30.
    Park JW, Roh JL, Lee SW, Kim SB, Choi SH, Nam SY. Effect of polypharmacy and potentially inappropriate medications on treatment and posttreatment courses in elderly patients with head and neck cancer. J Cancer Res Clin Oncol. 2016;142(5):1031–40.Google Scholar
  31. 31.
    Sutaria A, Liu L, Ahmed Z. Multiple medication (polypharmacy) and chronic kidney disease in patients aged 60 and older: a pharmacoepidemiologic perspective. Ther Adv Cardiovas Dis. 2016;10(4):242–50.Google Scholar
  32. 32.
    Oyarzun-Gonzalez XA, Taylor KC, Myers SR, Muldoon SB, Baumgartner RN. Cognitive decline and polypharmacy in an elderly population. J Am Geriatr Soc. 2015;63(2):397–9.Google Scholar
  33. 33.
    Pamoukdjian F, Aparicio T, Zelek L, Boubaya M, Caillet P, François V, et al. Impaired mobility, depressed mood, cognitive impairment and polypharmacy are independently associated with disability in older cancer outpatients: the prospective physical frailty in elderly Cancer patients (PF-EC) cohort study. J Geriatr Oncol. 2017;8(3):190–5.Google Scholar
  34. 34.
    Resnick B, Galik E, Boltz M, Holmes S, Fix S, Vigne E, et al. Polypharmacy in assisted living and impact on clinical outcomes. Consult Pharm. 2018;33(6):321–30.Google Scholar
  35. 35.
    Masumoto S, Sato M, Maeno T, Ichinohe Y, Maeno T. Potentially inappropriate medications with polypharmacy increase the risk of falls in older Japanese patients: 1-year prospective cohort study. Geriatr Gerontol Int. 2018;18(7):1064–70.Google Scholar
  36. 36.
    Lim LM, McStea WW, Nor Azmi N, Abdul Aziz SA, Alwi S, Kamarulzaman A, et al. Prevalence, risk factors and health outcomes associated with polypharmacy among urban community-dwelling older adults in multiethnic Malaysia. PLoS One. 2017;12(3):e0173466.Google Scholar
  37. 37.
    Thelen JM, Lunch SG, Bruce AS, Hancock LM, Bruce JM. Polypharmacy in multiple sclerosis: relationship with fatigue, perceived cognition, and objective cognitive performance. J Psychosom Res. 2014;76(5):400–4.Google Scholar
  38. 38.
    Abe T, Tamiya N, Kitahara T, Tojuda Y. Polypharmacy as a risk factor for hospital admission among ambulance-transported old-old patients. Acute Med Surg. 2015;3(2):107–13.Google Scholar
  39. 39.
    • Franchi C, Marcucci M, Mannucci PM, Tettamanti M, Pasina L, Fortino I, et al. Changes in clinical outcomes for community-dwelling older people exposed to incident chronic polypharmacy: a comparison between 2001 and 2009. Pharmacoepidemiol Drug Saf. 2016;25(2):204–11 Incident polypharmacy is evaluated in this study.Google Scholar
  40. 40.
    Leiss W, Méan M, Limacher A, Righini M, Jaeger K, Beer HJ, et al. Polypharmacy is associated with an increased risk of bleeding in elderly patients with venous thromboembolism. J Gen Intern Med. 2015;30(1):17–24.Google Scholar
  41. 41.
    Martinez-Gomez D, Guallar-Castillon P, Higueras-Fresnillo S, Banegas JR, Sadarangani KP, Rodriguez-Artelejo F. A healthy lifestyle attenuates the effect of polypharmacy on total and cardiovascular mortality: a national prospective cohort study. Sci Rep. 2018;8(1):12615.  https://doi.org/10.1038/s41598-018-30840-9.
  42. 42.
    Schoufour JD, Oppewal A, van der Maarl HJK, Hermans H, Evenhuis HM, Hilgenkamp TIM, et al. Multimorbidity and polypharmacy are independently associated with mortality in older people with intellectual disabilities: a 5-year follow-up from the HA-ID study. Am J Intellect Dev Disabil. 2018;123(1):72–82.Google Scholar
  43. 43.
    Catapano JS, Chapman AJ, Horner LP, Lu M, Fraser DR, Fildes JJ. Pre-injury polypharmacy predicts mortality in isolated severe traumatic brain injury patients. Am J Surg. 2017;213(6):1104–8.Google Scholar
  44. 44.
    Bonaga B, Sanchez-Jurado PM, Martinez-Reig M, Ariza G, Rodriguez-Manas L, Gnjidic D, et al. Frailty, polypharmacy, and health outcomes in older adults: the frailty and dependence in Albacete study. J Am Med Dir Assoc. 2018;19(1):46–52.Google Scholar
  45. 45.
    Iurlo A, Nobili A, Latagliata R, Bucelli C, Castagnetti F, Breccia M, et al. Imatinib and polypharmacy in very old patients with chronic myeloid leukemia: effects on response rate, toxicity and outcome. Oncotarget. 2016;7(48):80083–90.Google Scholar
  46. 46.
    Lewandowski-Romps L, Schroeder HM, Berglund PA, Colpe LJ, Cox K, Hauret K, et al. Medical-encounter mental health diagnoses, non-fatal injury and polypharmacy indicators of risk for accident death in the US Army enlisted soldiers, 2004–2009. Prev Med. 2018;111:299–306.Google Scholar
  47. 47.
    Köning M, Spira D, Ilja D, Steinhagen-Thiessen E, Norman K. Polypharmacy as a risk factor for clinically relevant sarcopenia: Results from the Berlin Aging Study II. J Gerontol A Biol Sci Med Sci. 2017;73(1):117–22.Google Scholar
  48. 48.
    Okada M, Okada K, Fujii K. Influence of polypharmacy on heart rate variability in older adults at the Hiroshima atomic bomb survivors recuperation research center, Japan. PloS One. 2018;13(12):e0209081.Google Scholar
  49. 49.
    Meraya AM, Dwibedi N, Sambamoorthi U. Polypharmacy and health-related quality of life among US adults with arthritis, medical expenditure panel survey, 2010-2012. Prev Chronic Dis. 2016;13:E132.Google Scholar
  50. 50.
    Lalic S, Sluggett JK, Ilomäki J, Wimmer BC, Tan EC, Robson L, et al. Polypharmacy and medication regimen complexity as risk factors for hospitalization among residents of long-term care facilities: A prospective cohort study. J Am Med Dir Assoc. 2016;17(11):1067.e1–6.Google Scholar
  51. 51.
    Wimmer BC, Dent E, Visvanathan R, Wiese MD, Johnell K, Chapman I, et al. Polypharmacy and medication regimen complexity as factors associated with hospital discharge destination among older people: a prospective cohort study. Drugs Aging. 2014;31(8):623–30.Google Scholar
  52. 52.
    Razavi D, Lindblad M, Bexelius T, Oskarsson V, Sadr-Azodi O, Ljung R. Polypharmacy and risk of acute pancreatitis. Pharmacoepidemiol Drug Saf. 2016;25(11):1337–41.Google Scholar
  53. 53.
    Appleton SC, Abel GA, Payne RA. Cardiovascular polypharmacy is not associated with unplanned hospitalisation: evidence from a retrospective cohort study. BMC Fam Pract. 2014;15:58.Google Scholar
  54. 54.
    Gomez C, Vega-Quiroga S, Bermego-Pareja F, Medrano MJ, Louis ED, Benito-Leon J. Polyparmacy in the elderly: a marker of increased risk of mortality in a population-based prospective study (NEDICES). Gerontology. 2015;61(4):301–9.Google Scholar
  55. 55.
    Woopen H, Richter R, Ismaeel F, Chekerov R, Roots I, Siepmann T, et al. The influence of polypharmacy on grade III/IV toxicity, prior discontinuation of chemotherapy and overall survival in ovarian cancer. Gynecol Oncol. 2016;140(3):554–8.Google Scholar
  56. 56.
    Elliot K, Tooze JA, Geller R, Powell BL, Pardee TS, Ritchie E, et al. The prognostic importance of polypharmacy in older adults treated for acute myelogenous leukemia (AML). Leuk Res. 2014;38(10):1184–90.Google Scholar
  57. 57.
    Secora A, Alexander GC, Ballew SH, Coresh J, Grams ME. Kidney function, polypharmacy, and potentially inappropriate medication use in a community-based cohort of older adults. Drugs Aging. 2018;35(8):735–50.Google Scholar
  58. 58.
    Mueller C, Molokhia M, Perera G, Veronese N, Stubbs B, Shetty H, et al. Polypharmacy in people with dementia: associations with adverse health outcomes. Exp Gerontol. 2018;106:240–5.Google Scholar
  59. 59.
    Veronese N, Stubbs B, Noale M, Solmi M, Pilotto A, Vaona A, et al. Polypharmacy is associated with higher frailty risk in older people: an 8-year longitudinal cohort study. J Am Med Dir Assoc. 2017;18(7):624–8.Google Scholar
  60. 60.
    Filkova M, Carvalho J, Norton S, Scott D, Mant T, Molokhia M, et al. Polypharmacy and unplanned hospitalizations in patients with rheumatoid arthritis. J Rheumatol. 2017;44(12):1786–93.Google Scholar
  61. 61.
    Eggebrecht L, Nagler M, Göbel S, Lamparter H, Keller K, Wagner B, et al. Relevance of polypharmacy for clinical outcome in patients receiving vitamin K antagonists. J Am Geriatr Soc. 2019;67:463–70.Google Scholar
  62. 62.
    Wozniak I, Kolonko A, Chudek J, Nowak L, Farnik M, Wiecek A. Influence of polypharmacy on the quality of life in stable kidney transplant recipients. Transplant Proc. 2018;50(6):1896–9.Google Scholar
  63. 63.
    Gencer MZ, Arica S. Use of polypharmacy and herbal medication on quality of life in elderly patients at Okmeydani hospital’s polyclinics in Istanbul, Turkey. J Pak Med Assoc. 2017;67:895.Google Scholar
  64. 64.
    Justice AC, Gordon KS, Shanderson M, Edelman EJ, Argün KM, Gilbert CL, et al. Nonantiretroviral polypharmacy and adverse health outcomes among HIV-infected and uninfected individuals. AIDS. 2018;32(6):739–49.Google Scholar
  65. 65.
    Dhalwani NN, Fahami R, Sathanapally H, Seidu S, Davies MJ, Khunti K. Association between polypharmacy and falls in older adults: a longitudinal study from England. BMJ Open. 2017;7(10):e016358.Google Scholar
  66. 66.
    Pan HH, Li CY, Chen TJ, Su TP, Wang KY. Association of polypharmacy with fall-related fractures in older Taiwanese people: age- and gender-specific analyses. BMJ Open. 2014;4(3):e004428.Google Scholar
  67. 67.
    Rawle MJ, Cooper R, Kuh D, Richards M. Association between polypharmacy and cognitive and physical capability: a British birth cohort study. J Am Geriatr Soc. 2018;66(5):916–23.Google Scholar
  68. 68.
    Abe J, Umetsu R, Uranishi H, Suzuki H, Nishibata Y, Kato Y, et al. Analysis of polypharmacy effects in older patients using Japanese adverse drug event report database. PLoS One. 2017;12(12):e0190102.Google Scholar
  69. 69.
    Park HY, Park JW, Song HJ, Sohn HS, Kwon JW. The association between polypharmacy and dementia: a nested case-control study based on a 12-year longitudinal cohort database in South Korea. PLoS One. 2017;12(1):e0169463.Google Scholar
  70. 70.
    Herr M, Sirven N, Grondin H, Pichetti S, Sermet C. Frailty, polypharmacy and potentially inappropriate medications in old people: findings in a representative sample of the French population. Eur J Clin Pharmacol. 2017;73(9):1165–72.Google Scholar
  71. 71.
    Saum KU, Schöttker B, Meid AD, Holleczek B, Haefeli WE, Hauer K, et al. Is polypharmacy associated with frailty in older people? Results from the ESTHER cohort study. J Am Geriatr Soc. 2017;65(2):e27–32.Google Scholar
  72. 72.
    Park HY, Sohn HS, Kwon JW. The association between polypharmacy and hip fracture in osteoporotic women: a nested case–control study in South Korea. Clin Drug Investig. 2019;39:63–71.Google Scholar
  73. 73.
    Lu WH, Wen YW, Chen LK, Hsiao FY. Effect of polypharmacy, potentially inappropriate medications and anticholinergic burden on clinical outcomes: a retrospective cohort study. CMAJ. 2015;187:E130–7.Google Scholar
  74. 74.
    Poudel A, Peel NM, Nissen LM, Mitchell CA, Gray LC, Hubbard RE. Adverse outcomes in relation to polypharmacy in robust and frail older hospital patients. J Am Med Dir Assoc. 2016;17(8):767.e9–767.e13.Google Scholar
  75. 75.
    Schöttker B, Saum KU, Muhlack DC, Hoppe LK, Holleczek B, Brenner H. Polypharmacy and mortality: new insights from a large cohort of older adults by detection of effect modification by multi-morbidity and comprehensive correction of confounding by indication. Eur J Clin Pharmacol. 2017;73(8):1041–8.Google Scholar
  76. 76.
    Herr M, Robine JM, Pinot J, Arvieu JJ, Ankri J. Polypharmacy and frailty: prevalence, relationship, and impact on mortality in a French sample of 2350 old people. Pharmacoepidemiol Drug Saf. 2015;24:637–46.Google Scholar
  77. 77.
    Park HY, Park JW, Sohn HS, Kwon JW. Association of parkinsonism or Parkinson disease with polypharmacy in the year preceding diagnosis: a nested case-control study in South Korea. Drug Saf. 2017;40(11):1109–18.Google Scholar
  78. 78.
    Vetrano DL, Villani ER, Grande G, Giovanni S, Cipriani MC, Manes-Gravina E, et al. Association of polypharmacy with 1-year trajectories of cognitive and physical function in nursing home residents: results from a multicenter European study. J Am Med Dir Assoc. 2018;19(8):710–3.Google Scholar
  79. 79.
    George C, Verghese J. Polypharmacy and gait performance in community-dwelling older adults. J Am Geriatr Soc. 2017;65(9):2082–7.Google Scholar
  80. 80.
    Moorey HC, Zaidman S, Jackson TA. Delirium is not associated with anticholinergic burden or polypharmacy in older patients on admission to an acute hospital: an observational case control study. BMC Geriatr. 2016;16(1):162.Google Scholar
  81. 81.
    Rosted E, Schultz M, Sanders S. Frailty and polypharmacy in elderly patients are associated with a high readmission risk. Dan Med J. 2016;63(9):A5274.Google Scholar
  82. 82.
    Diez-Manglano J, Gimenez-Lopez M, Garces-Horna V, Sevil-Puras M, Castellar-Otin E, Gonzalez-Garcia P, et al. Excessive polypharmacy and survival in polypathological patients. Eur J Clin Pharmacol. 2015;71(6):733–9.Google Scholar
  83. 83.
    Gnjidic D, Hilmer SN, Blyth FM, Naganathan V, Waite L, Seibel MJ, et al. Polypharmacy cutoff and outcomes: five or more medicines were used to identify community-dwelling older men at risk of different adverse outcomes. J Clin Epidemiol. 2012;65(9):989–95.Google Scholar
  84. 84.
    Greenland S. Analysis of polytomous exposures and outcomes. In: Rothman K, Greenland S, Lash TL, editors. Modern epidemiology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008.Google Scholar
  85. 85.
    • Wastesson JW, Morin L, Laroche ML, Johnell K. How chronic is polypharmacy in old age? A longitudinal nationwide cohort study. J Am Geriatr Soc. 2019;67(3):455–62 Demonstration that polypharmacy is not a constant exposure.Google Scholar
  86. 86.
    von Buedingen F, Hammer MS, Meid AD, Müller WE, Gerlach FM, Muth C. Changes in prescribed medicines in older patients with multimorbidity and polypharmacy in general practice. BMC Fam Pract. 2018;19(1):131.  https://doi.org/10.1186/s12875-018-0825-3.
  87. 87.
    Wang YJ, Chiang SC, Lee PC, Chen YC, Chou LF, Chou YC, et al. Is excessive polypharmacy a transient or persistent phenomenon? A nationwide cohort study in Taiwan. Front Pharmacol. 2018;9:120.Google Scholar
  88. 88.
    Monégat M, Sermet C, Perronnin M, Rococo E. Polypharmacy : Definitions, measurements and stakes involved. Review of the literature and measurement tests. Questions d’économie de la santé, no 2014, December 2014. Available at: http://www.irdes.fr/english/issues-in-health-economics/204-polypharmacy- definitions-measurement-and-stakes-involved.pdf.
  89. 89.
    • Chiapella LC, Montemarani Menna J, Mamprin ME. Assessment of polypharmacy in elderly patients by using data from dispensed medications in community pharmacies: analysis of results by using different methods of estimation. Int J Clin Pharm. 2018;40(5):987–90 Illustration that exposure definition influences polypharmacy.Google Scholar
  90. 90.
    Sirois C, Lunghi C, Laroche ML, Maheux A, Frini A. The delicate choice of optimal basic therapy for multimorbid older adults: a cross-sectional survey. Res Social Adm Pharm. 2019;15:761–6.Google Scholar
  91. 91.
    Duerden M, Avery T, Payne R. Polypharmacy and medicines optimisation. Making it safe and sound. The King’s Fund. 2013.Google Scholar
  92. 92.
    Patterson SM, Cadogan CA, Kerse N, Cardwell CR, Bradely MC, Ryan C, et al. Interventions to improve the appropriate use of polypharmacy for older people. Cochrane Database Syst Rev. 2018;9:CD008165.Google Scholar
  93. 93.
    Burt J, Elmore N, Campbell SM, Rodgers S, Avery AJ, Payne RA. Developing a measure of polypharmacy appropriateness in primary care: systematic review and expert consensus study. BMC Med. 2018;16:91.  https://doi.org/10.1186/s12916-018-1078-7.
  94. 94.
    Holmes HM, Hayley DC, Alexander GC, Sachs GA. Reconsidering medication appropriateness for patients late in life. Arch Intern Med. 2006;166(6):605–9.Google Scholar
  95. 95.
    Kadam UT, Roberts I, White S, Bednall R, Khunti K, Nilsson PM, et al. Conceptualizing multiple drug use in patients with comorbidity and multimorbidity: proposal for standard definitions beyond the term polypharmacy. J Clin Epidemiol. 2019;106:98–107.Google Scholar
  96. 96.
    Nobili A, Marengoni A, Tettamanti M, Salerno F, Pasina L, Franchi C, et al. Association between clusters of diseases and polypharmacy in hospitalized elderly patients: results from the REPOSI study. Eur J Intern Med. 2011;22(6):597–602.Google Scholar
  97. 97.
    Haefeli WE, Meid AD. Pill-count and the arithmetic of risk: evidence that polypharmacy is a health status marker rather than a predictive surrogate for the risk of adverse drug events. Int J Clin Pharmacol Ther. 2018;56(12):572–6.Google Scholar
  98. 98.
    •• Wastesson JW, Morin L, Tan ECK, Johnell K. An update on the clinical consequences of polypharmacy in older adults: a narrative review. Expert Opin Drug Saf. 2018;17(12):1185–96 The study evaluates recent outcomes associated with polypharmacy and highlights some challenges that have to be addressed regarding polypharmacy.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Caroline Sirois
    • 1
    • 2
    • 3
    • 4
    Email author
  • Marc Simard
    • 4
  • Emmanuelle Gosselin
    • 1
    • 2
    • 3
  • Marie-Eve Gagnon
    • 1
    • 2
    • 3
  • Barbara Roux
    • 5
    • 6
  • Marie-Laure Laroche
    • 5
    • 6
  1. 1.Department of Social and Preventive MedicineLaval UniversityQuebecCanada
  2. 2.Centre of Excellence on Aging of QuebecCIUSSS-CNQuebecCanada
  3. 3.Centre de recherche sur les soins et les services de première ligne de l’Université LavalQuebecCanada
  4. 4.Institut national de santé publique du QuébecQuebecCanada
  5. 5.Centre of Pharmacovigilance and PharmacoepidemiologyUniversity Hospital of LimogesLimogesFrance
  6. 6.INSERM UMR 1248, Faculty of MedicineUniversity of LimogesLimogesFrance

Personalised recommendations