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Drugs & Aging

, Volume 35, Issue 6, pp 523–538 | Cite as

Anticholinergic Drug Burden Tools/Scales and Adverse Outcomes in Different Clinical Settings: A Systematic Review of Reviews

  • Tomas J. Welsh
  • Veronika van der Wardt
  • Grace Ojo
  • Adam L. Gordon
  • John R. F. Gladman
Systematic Review

Abstract

Background

Cumulative anticholinergic exposure (anticholinergic burden) has been linked to a number of adverse outcomes. To conduct research in this area, an agreed approach to describing anticholinergic burden is needed.

Objective

This review set out to identify anticholinergic burden scales, to describe their rationale, the settings in which they have been used and the outcomes associated with them.

Methods

A search was performed using the Healthcare Databases Advanced Search of MEDLINE, EMBASE, Cochrane, CINAHL and PsycINFO from inception to October 2016 to identify systematic reviews describing anticholinergic burden scales or tools. Abstracts and titles were reviewed to determine eligibility for review with eligible articles read in full. The final selection of reviews was critically appraised using the ROBIS tool and pre-defined data were extracted; the primary data of interest were the anticholinergic burden scales or tools used.

Results

Five reviews were identified for analysis containing a total of 62 original articles. Eighteen anticholinergic burden scales or tools were identified with variation in their derivation, content and how they quantified the anticholinergic activity of medications. The Drug Burden Index was the most commonly used scale or tool in community and database studies, while the Anticholinergic Risk Scale was used more frequently in care homes and hospital settings. The association between anticholinergic burden and clinical outcomes varied by index and study. Falls and hospitalisation were consistently found to be associated with anticholinergic burden. Mortality, delirium, physical function and cognition were not consistently associated.

Conclusions

Anticholinergic burden scales vary in their rationale, use and association with outcomes. This review showed that the concept of anticholinergic burden has been variably defined and inconsistently described using a number of indices with different content and scoring. The association between adverse outcomes and anticholinergic burden varies between scores and has not been conclusively established.

Notes

Compliance with Ethical Standards

Funding

No sources of funding were used to assist in the preparation of this article.

Conflict of Interest

Tomas Welsh, Veronika Van der Wardt, Grace Ojo, Adam Gordon and John Gladman have no conflicts of interest directly relevant to the content of this review.

Supplementary material

40266_2018_549_MOESM1_ESM.docx (29 kb)
Supplementary material 1 (DOCX 28 kb)

References

  1. 1.
    Salahudeen MS, Duffull SB, Nishtala PS. Anticholinergic burden quantified by anticholinergic risk scales and adverse outcomes in older people: a systematic review. BMC Geriatr. 2015;15:31.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Cardwell K, Hughes CM, Ryan C. The association between anticholinergic medication burden and health related outcomes in the ‘oldest old’: a systematic review of the literature. Drugs Aging. 2015;32(10):835–48.CrossRefPubMedGoogle Scholar
  3. 3.
    Durán CE, Azermai M, Vander Stichele RH. Systematic review of anticholinergic risk scales in older adults. Eur J Clin Pharmacol. 2013;69(7):1485–96.CrossRefPubMedGoogle Scholar
  4. 4.
    Zimmerman KM, Salow M, Skarf LM, et al. Increasing anticholinergic burden and delirium in palliative care inpatients. Palliat Med. 2014;28(4):335–41.CrossRefPubMedGoogle Scholar
  5. 5.
    Ancelin ML, Artero S, Portet F, et al. Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study. BMJ. 2006;332(7539):455–9.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Carnahan RM, Lund BC, Perry PJ, et al. The relationship of an anticholinergic rating scale with serum anticholinergic activity in elderly nursing home residents. Psychopharmacol Bull. 2002;36(4):14–9.PubMedGoogle Scholar
  7. 7.
    Villalba-Moreno AM, Alfaro-Lara ER, Pérez-Guerrero MC, et al. Systematic review on the use of anticholinergic scales in poly pathological patients. Arch Gerontol Geriatr. 2016;62:1–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Gnjidic D, Hilmer SN, Blyth FM, 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.CrossRefPubMedGoogle Scholar
  9. 9.
    Campbell NL, Perkins AJ, Bradt P, et al. Association of anticholinergic burden with cognitive impairment and health care utilization among a diverse ambulatory older adult population. Pharmacotherapy. 2016;36(11):1123–31.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Mayer T, Haefeli WE, Seidling HM. Different methods, different results–how do available methods link a patient’s anticholinergic load with adverse outcomes? Eur J Clin Pharmacol. 2015;71(11):1299–314.CrossRefPubMedGoogle Scholar
  11. 11.
    Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Whiting P, Savović J, Higgins JP, et al. ROBIS: a new tool to assess risk of bias in systematic reviews was developed. J Clin Epidemiol. 2016;69:225–34.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Aizenberg D, Sigler M, Weizman A, et al. Anticholinergic burden and the risk of falls among elderly psychiatric inpatients: a 4-year case-control study. Int Psychogeriatr. 2002;14(3):307–10.CrossRefPubMedGoogle Scholar
  14. 14.
    Ehrt U, Broich K, Larsen JP, et al. Use of drugs with anticholinergic effect and impact on cognition in Parkinson’s disease: a cohort study. J Neurol Neurosurg Psychiatry. 2010;81(2):160–5.CrossRefPubMedGoogle Scholar
  15. 15.
    Kolanowski A, Fick DM, Campbell J, et al. A preliminary study of anticholinergic burden and relationship to a quality of life indicator, engagement in activities, in nursing home residents with dementia. J Am Med Dir Assoc. 2009;10(4):252–7.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Campbell NL, Boustani MA, Lane KA, et al. Use of anticholinergics and the risk of cognitive impairment in an African American population. Neurology. 2010;75(2):152–9.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Campbell NL, Khan BA, Farber M, et al. Improving delirium care in the intensive care unit: the design of a pragmatic study. Trials. 2011;12:139.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Fox C, Livingston G, Maidment ID, et al. The impact of anticholinergic burden in Alzheimer’s dementia-the LASER-AD study. Age Ageing. 2011;40(6):730–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Fox C, Richardson K, Maidment ID, et al. Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study. J Am Geriatr Soc. 2011;59(8):1477–83.CrossRefPubMedGoogle Scholar
  20. 20.
    Cai X, Campbell N, Khan BC, et al. Long-term anticholinergic use and the aging brain. Alzheimers Dement. 2013;9(4):377–85.CrossRefPubMedGoogle Scholar
  21. 21.
    Koyama A, Steinman M, Ensrud K, et al. Long-term cognitive and functional effects of potentially inappropriate medications in older women. J Gerontol A Biol Sci Med Sci. 2014;69(4):423–9.CrossRefPubMedGoogle Scholar
  22. 22.
    Koyama A, Steinman M, Ensrud K, et al. Ten-year trajectory of potentially inappropriate medications in very old women: importance of cognitive status. J Am Geriatr Soc. 2013;61(2):258–63.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Pasina L, Djade CD, Lucca U, et al. Association of anticholinergic burden with cognitive and functional status in a cohort of hospitalized elderly: comparison of the anticholinergic cognitive burden scale and anticholinergic risk scale: results from the REPOSI study. Drugs Aging. 2013;30(2):103–12.CrossRefPubMedGoogle Scholar
  24. 24.
    Shah RC, Janos AL, Kline JE, et al. Cognitive decline in older persons initiating anticholinergic medications. PLoS ONE. 2013;8(5):e64111.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kidd AC, Musonda P, Soiza RL, et al. The relationship between total anticholinergic burden (ACB) and early in-patient hospital mortality and length of stay in the oldest old aged 90 years and over admitted with an acute illness. Arch Gerontol Geriatr. 2014;59(1):155–61.CrossRefPubMedGoogle Scholar
  26. 26.
    Kashyap M, Belleville S, Mulsant BH, et al. Methodological challenges in determining longitudinal associations between anticholinergic drug use and incident cognitive decline. J Am Geriatr Soc. 2014;62(2):336–41.CrossRefPubMedGoogle Scholar
  27. 27.
    Mangoni AA, van Munster BC, Woodman RJ, et al. Measures of anticholinergic drug exposure, serum anticholinergic activity, and all-cause postdischarge mortality in older hospitalized patients with hip fractures. Am J Geriatr Psychiatry. 2013;21(8):785–93.CrossRefPubMedGoogle Scholar
  28. 28.
    Lanctôt KL, O’Regan J, Schwartz Y, et al. Assessing cognitive effects of anticholinergic medications in patients with coronary artery disease. Psychosomatics. 2014;55(1):61–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Sittironnarit G, Ames D, Bush AI, et al. Effects of anticholinergic drugs on cognitive function in older Australians: results from the AIBL study. Dement Geriatr Cogn Disord. 2011;31(3):173–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Carnahan RM, Lund BC, Perry PJ, et al. The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity. J Clin Pharmacol. 2006;46(12):1481–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Kersten H, Molden E, Tolo IK, et al. Cognitive effects of reducing anticholinergic drug burden in a frail elderly population: a randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2013;68(3):271–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Kersten H, Molden E, Willumsen T, et al. Higher anticholinergic drug scale (ADS) scores are associated with peripheral but not cognitive markers of cholinergic blockade: cross sectional data from 21 Norwegian nursing homes. Br J Clin Pharmacol. 2013;75(3):842–9.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Lampela P, Lavikainen P, Garcia-Horsman JA, et al. Anticholinergic drug use, serum anticholinergic activity, and adverse drug events among older people: a population-based study. Drugs Aging. 2013;30(5):321–30.CrossRefPubMedGoogle Scholar
  34. 34.
    Low LF, Anstey KJ, Sachdev P. Use of medications with anticholinergic properties and cognitive function in a young-old community sample. Int J Geriatr Psychiatry. 2009;24(6):578–84.CrossRefPubMedGoogle Scholar
  35. 35.
    Juliebø V, Bjøro K, Krogseth M, et al. Risk factors for preoperative and postoperative delirium in elderly patients with hip fracture. J Am Geriatr Soc. 2009;57(8):1354–61.CrossRefPubMedGoogle Scholar
  36. 36.
    Drag L, Wright S, Bieliauskas L. Prescribing practices of anticholinergic medications and their association with cognition in an extended care setting. J Appl Gerontol. 2012;31(2):239–59.CrossRefGoogle Scholar
  37. 37.
    Kalisch Ellett LM, Pratt NL, Ramsay EN, et al. Multiple anticholinergic medication use and risk of hospital admission for confusion or dementia. J Am Geriatr Soc. 2014;62(10):1916–22.CrossRefPubMedGoogle Scholar
  38. 38.
    Rudolph JL, Salow MJ, Angelini MC, et al. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. 2008;168(5):508–13.CrossRefPubMedGoogle Scholar
  39. 39.
    Kumpula EK, Bell JS, Soini H, et al. Anticholinergic drug use and mortality among residents of long-term care facilities: a prospective cohort study. J Clin Pharmacol. 2011;51(2):256–63.CrossRefPubMedGoogle Scholar
  40. 40.
    Lowry E, Woodman RJ, Soiza RL, et al. Associations between the anticholinergic risk scale score and physical function: potential implications for adverse outcomes in older hospitalized patients. J Am Med Dir Assoc. 2011;12(8):565–72.CrossRefPubMedGoogle Scholar
  41. 41.
    Lowry E, Woodman RJ, Soiza RL, et al. Clinical and demographic factors associated with antimuscarinic medication use in older hospitalized patients. Hosp Pract. 2011;39(1):30–6.CrossRefGoogle Scholar
  42. 42.
    Koshoedo S, Soiza RL, Purkayastha R, et al. Anticholinergic drugs and functional outcomes in older patients undergoing orthopaedic rehabilitation. Am J Geriatr Pharmacother. 2012;10(4):251–7.CrossRefPubMedGoogle Scholar
  43. 43.
    Landi F, Dell’Aquila G, Collamati A, et al. Anticholinergic drug use and negative outcomes among the frail elderly population living in a nursing home. J Am Med Dir Assoc. 2014;15(11):825–9.CrossRefPubMedGoogle Scholar
  44. 44.
    Huang K, Chan F, Shih H, et al. Relationship between potentially inappropriate anticholinergic drugs (PIADs) and adverse outcomes among elderly patients in Taiwan. J Food Drug Anal. 2012;20(4):930–7.Google Scholar
  45. 45.
    Bostock CV, Soiza RL, Mangoni AA. Associations between different measures of anticholinergic drug exposure and Barthel Index in older hospitalized patients. Ther Adv Drug Saf. 2013;4(6):235–45.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Dispennette R, Elliott D, Nguyen L, et al. Drug Burden Index score and anticholinergic risk scale as predictors of readmission to the hospital. Consult Pharm. 2014;29(3):158–68.CrossRefPubMedGoogle Scholar
  47. 47.
    Teramura-Grönblad M, Muurinen S, Soini H, et al. Use of anticholinergic drugs and cholinesterase inhibitors and their association with psychological well-being among frail older adults in residential care facilities. Ann Pharmacother. 2011;45(5):596–602.CrossRefPubMedGoogle Scholar
  48. 48.
    Walter PJ, Dieter AA, Siddiqui NY, et al. Perioperative anticholinergic medications and risk of catheterization after urogynecologic surgery. Female Pelvic Med Reconstr Surg. 2014;20(3):163–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Cancelli I, Valentinis L, Merlino G, et al. Drugs with anticholinergic properties as a risk factor for psychosis in patients affected by Alzheimer’s disease. Clin Pharmacol Ther. 2008;84(1):63–8.CrossRefPubMedGoogle Scholar
  50. 50.
    Cancelli I, Gigli GL, Piani A, et al. Drugs with anticholinergic properties as a risk factor for cognitive impairment in elderly people: a population-based study. J Clin Psychopharmacol. 2008;28(6):654–9.CrossRefPubMedGoogle Scholar
  51. 51.
    Chew ML, Mulsant BH, Pollock BG, et al. Anticholinergic activity of 107 medications commonly used by older adults. J Am Geriatr Soc. 2008;56(7):1333–41.CrossRefPubMedGoogle Scholar
  52. 52.
    Jessen F, Kaduszkiewicz H, Daerr M, et al. Anticholinergic drug use and risk for dementia: target for dementia prevention. Eur Arch Psychiatry Clin Neurosci. 2010;260(Suppl. 2):S111–5.CrossRefPubMedGoogle Scholar
  53. 53.
    Han L, Agostini JV, Allore HG. Cumulative anticholinergic exposure is associated with poor memory and executive function in older men. J Am Geriatr Soc. 2008;56(12):2203–10.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Agar M, Currow D, Plummer J, et al. Changes in anticholinergic load from regular prescribed medications in palliative care as death approaches. Palliat Med. 2009;23(3):257–65.CrossRefPubMedGoogle Scholar
  55. 55.
    Yeh YC, Liu CL, Peng LN, et al. Potential benefits of reducing medication-related anticholinergic burden for demented older adults: a prospective cohort study. Geriatr Gerontol Int. 2013;13(3):694–700.CrossRefPubMedGoogle Scholar
  56. 56.
    Han L, McCusker J, Cole M, et al. Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients. Arch Intern Med. 2001;161(8):1099–105.CrossRefPubMedGoogle Scholar
  57. 57.
    Best O, Gnjidic D, Hilmer SN, et al. Investigating polypharmacy and drug burden index in hospitalised older people. Intern Med J. 2013;43(8):912–8.CrossRefPubMedGoogle Scholar
  58. 58.
    Gnjidic D, Cumming RG, Le Couteur DG, et al. Drug Burden Index and physical function in older Australian men. Br J Clin Pharmacol. 2009;68(1):97–105.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Gnjidic D, Le Couteur DG, Abernethy DR, et al. Drug burden index and Beers criteria: impact on functional outcomes in older people living in self-care retirement villages. J Clin Pharmacol. 2012;52(2):258–65.CrossRefPubMedGoogle Scholar
  60. 60.
    Gnjidic D, Le Couteur DG, Naganathan V, et al. Effects of drug burden index on cognitive function in older men. J Clin Psychopharmacol. 2012;32(2):273–7.CrossRefPubMedGoogle Scholar
  61. 61.
    Gnjidic D, Bell JS, Hilmer SN, et al. Drug Burden Index associated with function in community-dwelling older people in Finland: a cross-sectional study. Ann Med. 2012;44(5):458–67.CrossRefPubMedGoogle Scholar
  62. 62.
    Gnjidic D, Hilmer SN, Hartikainen S, et al. Impact of high risk drug use on hospitalization and mortality in older people with and without Alzheimer’s disease: a national population cohort study. PLoS ONE. 2014;9(1):e83224.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Wilson NM, Hilmer SN, March LM, et al. Associations between drug burden index and physical function in older people in residential aged care facilities. Age Ageing. 2010;39(4):503–7.CrossRefPubMedGoogle Scholar
  64. 64.
    Wilson NM, Hilmer SN, March LM, et al. Associations between drug burden index and falls in older people in residential aged care. J Am Geriatr Soc. 2011;59(5):875–80.CrossRefPubMedGoogle Scholar
  65. 65.
    Wilson NM, Hilmer SN, March LM, et al. Associations between drug burden index and mortality in older people in residential aged care facilities. Drugs Aging. 2012;29(2):157–65.CrossRefPubMedGoogle Scholar
  66. 66.
    Cao YJ, Mager DE, Simonsick EM, et al. Physical and cognitive performance and burden of anticholinergics, sedatives, and ACE inhibitors in older women. Clin Pharmacol Ther. 2008;83(3):422–9.CrossRefPubMedGoogle Scholar
  67. 67.
    Hilmer SN, Mager DE, Simonsick EM, et al. A drug burden index to define the functional burden of medications in older people. Arch Intern Med. 2007;167(8):781–7.CrossRefPubMedGoogle Scholar
  68. 68.
    Lowry E, Woodman RJ, Soiza RL, et al. Drug burden index, physical function, and adverse outcomes in older hospitalized patients. J Clin Pharmacol. 2012;52(10):1584–91.CrossRefPubMedGoogle Scholar
  69. 69.
    Lönnroos E, Gnjidic D, Hilmer SN, et al. Drug Burden Index and hospitalization among community-dwelling older people. Drugs Aging. 2012;29(5):395–404.CrossRefPubMedGoogle Scholar
  70. 70.
    Dauphinot V, Faure R, Omrani S, et al. Exposure to anticholinergic and sedative drugs, risk of falls, and mortality: an elderly inpatient, multicenter cohort. J Clin Psychopharmacol. 2014;34(5):565–70.CrossRefPubMedGoogle Scholar
  71. 71.
    Nishtala PS, Narayan SW, Wang T, et al. Associations of drug burden index with falls, general practitioner visits, and mortality in older people. Pharmacoepidemiol Drug Saf. 2014;23(7):753–8.CrossRefPubMedGoogle Scholar
  72. 72.
    Bosboom PR, Alfonso H, Almeida OP, et al. Use of potentially harmful medications and health-related quality of life among people with dementia living in residential aged care facilities. Dement Geriatr Cogn Dis Extra. 2012;2(1):361–71.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Minzenberg MJ, Poole JH, Benton C, et al. Association of anticholinergic load with impairment of complex attention and memory in schizophrenia. Am J Psychiatry. 2004;161(1):116–24.CrossRefPubMedGoogle Scholar
  74. 74.
    Whalley LJ, Sharma S, Fox HC, et al. Anticholinergic drugs in late life: adverse effects on cognition but not on progress to dementia. J Alzheimers Dis. 2012;30(2):253–61.CrossRefPubMedGoogle Scholar
  75. 75.
    Boustani M, Campbell N, Munger S, et al. Impact of anticholinergics on the aging brain: a review and practical application. Aging Health. 2008;4(3):311–20.CrossRefGoogle Scholar
  76. 76.
    Summers WK. A clinical method of estimating risk of drug induced delirium. Life Sci. 1978;22(17):1511–6.CrossRefPubMedGoogle Scholar
  77. 77.
    Mosby. Mosby’s drug consult for health professions. C.V. Mosby Publishing Co, Missouri; 2004.Google Scholar
  78. 78.
    Physicians’ desk reference. 58th ed. Montvale (NJ): Thomson PDR; 2016.Google Scholar
  79. 79.
    Gnjidic D, Hilmer SN, Blyth FM, et al. High-risk prescribing and incidence of frailty among older community-dwelling men. Clin Pharmacol Ther. 2012;91(3):521–8.CrossRefPubMedGoogle Scholar
  80. 80.
    Klamer TT, Wauters M, Azermai M, et al. A novel scale linking potency and dosage to estimate anticholinergic exposure in older adults: the Muscarinic Acetylcholinergic Receptor Antagonist Exposure Scale. Basic Clin Pharmacol Toxicol. 2017;120(6):582–90.CrossRefPubMedGoogle Scholar
  81. 81.
    Kouladjian L, Gnjidic D, Chen T, et al. DBI Calculator©. The Drug Burden Index Calculator  2016 [cited 2016 08 Nov 2016]; 1:[The Drug Burden Index Calculator]. Available from: https://drugburdenindex.com/Account/Login?ReturnUrl=%2f.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Research Institute for the Care of Older People (RICE)Royal United HospitalBathUK
  2. 2.Royal United Hospital Bath NHS Foundation TrustBathUK
  3. 3.University of NottinghamNottinghamUK
  4. 4.Derby Teaching Hospitals NHS Foundation TrustDerbyUK
  5. 5.Collaboration for Leadership in Applied Health Research and Care (CLAHRC) East MidlandsLeicesterUK
  6. 6.University of BristolBristolUK
  7. 7.NIHR Nottingham Biomedical Research CentreNottinghamUK

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