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Review

Anticholinergics: theoretical and clinical overview

, &
Pages 753-768 | Received 18 Dec 2015, Accepted 10 Mar 2016, Published online: 30 Mar 2016

References

  • 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):1333–1341.
  • Roe CM, Anderson MJ, Spivack B. Use of anticholinergic medications by older adults with dementia. J Am Geriatr Soc. 2002;50(5):836–842.
  • De Wilde S, Carey IM, Harris T, et al. Trends in potentially inappropriate prescribing amongst older UK primary care patients. Pharmacoepidemiol Drug Saf. 2007;16(6):658–667.
  • Peters NL. Snipping the thread of life. Antimuscarinic side effects of medications in the elderly. Arch Intern Med. 1989;149(11):2414–2420.
  • 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):321–330.
  • Carriere I, Fourrier-Reglat A, Dartigues JF, et al. Drugs with anticholinergic properties, cognitive decline, and dementia in an elderly general population: the 3-city study. Arch Intern Med. 2009;169(14):1317–1324.
  • Uusvaara J, Pitkala KH, Kautiainen H, et al. Association of anticholinergic drugs with hospitalization and mortality among older cardiovascular patients: a prospective study. Drugs Aging. 2011;28(2):131–138.
  • Gerretsen P, Pollock BG. Drugs with anticholinergic properties: a current perspective on use and safety. Expert Opin Drug Saf. 2011;10(5):751–765.
  • Tune LE, Egeli S. Acetylcholine and delirium. Dement Geriatr Cogn Disord. 1999;10(5):342–344.
  • 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(1):31.
  • 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):508–513.
  • Zarowitz BJ. Oral solid potassium chloride and anticholinergic medications: a new drug interaction for an old drug? Geriatr Nurs. 2006;27(6):329–333.
  • 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):311–320.
  • 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):1481–1486.
  • 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):455–459.
  • 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):160–165.
  • 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):173–178.
  • 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):2203–2210.
  • Hosoi M, Hori K, Konishi K, et al. Pharmacotherapy for neurocognitive disorders based on the hypothesis of endogenous appearance of anticholinergic activity. Neurodegener Dis. 2015;15(3):157–161.
  • Hori K, Konishi K, Tani M, et al. Serum anticholinergic activity: a possible peripheral marker of the anticholinergic burden in the central nervous system in Alzheimer’s disease. Dis Markers. 2014;2014:459013.
  • Hori K, Konishi K, Tani M, et al. Why does the progression of Alzheimer’s disease accelerate. Ann Psychiatry Ment Health. 2014;2(1):1006.
  • Konishi K, Hori K, Tani M, et al. Hypothesis of endogenous anticholinergic activity in Alzheimer’s disease. Neurodegener Dis. 2015;15(3):149–156.
  • Hori K, Konishi K, Akita R, et al. Proposal of endogenous anticholinergic hypothesis in Alzheimer disease. Nihon Shinkei Seishin Yakurigaku Zasshi. 2013;33(3):117–126.
  • Hori K, Hachisu M, Tomioka H, et al. Anticholinergic activity and Alzheimer’s disease. Neurodegener Dis. 2015;15(3):131–133.
  • Ahmed S, Leurent B, Sampson EL. Risk factors for incident delirium among older people in acute hospital medical units: a systematic review and meta-analysis. Age Ageing. 2014;43(3):326–333.
  • Siddiqi N, House AO, Holmes JD. Occurrence and outcome of delirium in medical in-patients: a systematic literature review. Age Ageing. 2006;35(4):350–364.
  • Salahudeen MS, Nishtala PS, Duffull SB. The influence of patient characteristics on anticholinergic events in older people. Dement Geriatr Cogn Dis Extra. 2015;5(3):530–541.
  • Tune LE. Anticholinergic effects of medication in elderly patients. J Clin Psychiatry. 2001;62 Suppl 21:11–14.
  • Kersten H, Wyller TB. Anticholinergic drug burden in older people’s brain - how well is it measured? Basic Clin Pharmacol Toxicol. 2014;114(2):151–159.
  • Parkinson L, Magin PJ, Thomson A, et al. Anticholinergic burden in older women: not seeing the wood for the trees? Med J Aust. 2015;202(2):91–94.
  • 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):781–787.
  • Lechevallier-Michel N, Molimard M, Dartigues JF, et al. Drugs with anticholinergic properties and cognitive performance in the elderly: results from the PAQUID Study. Br J Clin Pharmacol. 2005;59(2):143–151.
  • Nishtala PS, Fois RA, McLachlan AJ, et al. Anticholinergic activity of commonly prescribed medications and neuropsychiatric adverse events in older people. J Clin Pharmacol. 2009;49(10):1176–1184.
  • 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):422–429.
  • Hilmer SN, Mager DE, Simonsick EM, et al. Drug burden index score and functional decline in older people. Am J Med. 2009;122(12):1142–1149.e1-2.
  • 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.
  • Feinberg M. The problems of anticholinergic adverse effects in older patients. Drugs Aging. 1993;3(4):335–348.
  • Tune L, Carr S, Hoag E, et al. Anticholinergic effects of drugs commonly prescribed for the elderly: potential means for assessing risk of delirium. Am J Psychiatry. 1992;149(10):1393–1394.
  • Thomas C, Hestermann U, Kopitz J, et al. Serum anticholinergic activity and cerebral cholinergic dysfunction: an EEG study in frail elderly with and without delirium. BMC Neurosci. 2008;9:86.
  • de Leon J. Paying attention to pharmacokinetic and pharmacodynamic mechanisms to progress in the area of anticholinergic use in geriatric patients. Curr Drug Metab. 2011;12(7):635–646.
  • Shi S, Klotz U. Age-related changes in pharmacokinetics. Curr Drug Metab. 2011;12(7):601–610.
  • Montamat SC, Cusack BJ, Vestal RE. Management of drug therapy in the elderly. N Engl J Med. 1989;321(5):303–309.
  • Abrams P, Andersson KE, Buccafusco JJ, et al. Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder. Br J Pharmacol. 2006;148(5):565–578.
  • Mori K, Yamashita H, Nagao M, et al. Effects of anticholinergic drug withdrawal on memory, regional cerebral blood flow and extrapyramidal side effects in schizophrenic patients. Pharmacopsychiatry. 2002;35(1):6–11.
  • Cancelli I, Beltrame M, D’Anna L, et al. Drugs with anticholinergic properties: a potential risk factor for psychosis onset in Alzheimer’s disease? Expert Opin Drug Saf. 2009;8(5):549–557.
  • Whitehouse PJ, Price DL, Struble RG, et al. Alzheimer’s disease and senile dementia: loss of neurons in the basal forebrain. Science. 1982;215(4537):1237–1239.
  • Cummings JL. Cholinesterase inhibitors: a new class of psychotropic compounds. Am J Psychiatry. 2000;157(1):4–15.
  • Tsang SW, Pomakian J, Marshall GA, et al. Disrupted muscarinic M1 receptor signaling correlates with loss of protein kinase C activity and glutamatergic deficit in Alzheimer’s disease. Neurobiol Aging. 2007;28(9):1381–1387.
  • Cummings JL, Kaufer D. Neuropsychiatric aspects of Alzheimer’s disease: the cholinergic hypothesis revisited. Neurology. 1996;47(4):876–883.
  • Staskin DR, Zoltan E. Anticholinergics and central nervous system effects: are we confused? Rev Urol. 2007;9(4):191–196.
  • Adams BE, Manoguerra AS, Lilja GP, et al. Heat stroke associated with medications having anticholinergic effects. Minn Med. 1977;60(2):103–106.
  • Cassolato SF, Turnbull RS. Xerostomia: clinical aspects and treatment. Gerodontology. 2003;20(2):64–77.
  • Bostock CV, Soiza RL, Mangoni AA. Association between prescribing of antimuscarinic drugs and antimuscarinic adverse effects in older people. Expert Rev Clin Pharmacol. 2010;3(4):441–452.
  • Lieberman JA. Managing anticholinergic side effects. Prim Care Companion J Clin Psychiatry. 2004;6(suppl 2):20–23.
  • Blazer DG 2nd, Federspiel CF, Ray WA, et al. The risk of anticholinergic toxicity in the elderly: a study of prescribing practices in two populations. J Gerontol. 1983;38(1):31–35.
  • 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):1477–1483.
  • Mulsant BH, Pollock BG, Kirshner M, et al. Serum anticholinergic activity in a community-based sample of older adults: relationship with cognitive performance. Arch Gen Psychiatry. 2003;60(2):198–203.
  • Remillard AJ. A pilot project to assess the association of anticholinergic symptoms with anticholinergic serum levels in the elderly. Pharmacotherapy. 1994;14(4):482–487.
  • Chatterjee S, Palli SR, Mehta S, et al. Prevalence and predictors of anticholinergic medication use in elderly nursing home residents with dementia. Value in Health. 2010;13(3):A107–A108.
  • Wawruch M, Macugova A, Kostkova L, et al. The use of medications with anticholinergic properties and risk factors for their use in hospitalised elderly patients. Pharmacoepidemiol Drug Saf. 2012;21(2):170–176.
  • 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):257–265.
  • Tiwari P, Dwivedi S, Singh MP, et al. Basic and modern concepts on cholinergic receptor: a review. Asian Pac J Trop Dis. 2013;3(5):413–420.
  • Dharia SP The effect of anticholinergic burden on functional outcomes in patients with moderate to severe Alzheimer’s disease [VCU theses and dissertations]. Paper 2248. Richmond (VA): Virginia Commonwealth University Archives; 2010. http://scholarscompass.vcu.edu/etd/2248/?show=full
  • Gupta SK, Shah JC, Hwang SS. Pharmacokinetic and pharmacodynamic characterization of OROS® and immediate-release amitriptyline. Br J Clin Pharmacol. 1999;48(1):71–78.
  • Schmider J, Deuschle M, Schweiger U, et al. Amitriptyline metabolism in elderly depressed patients and normal controls in relation to hypothalamic-pituitary-adrenal system function. J Clin Psychopharmacol. 1995;15(4):250–258.
  • Dawling S, Lynn K, Rosser R, et al. Nortriptyline metabolism in chronic renal failure: metabolite elimination. Clin Pharmacol Ther. 1982;32(3):322–329.
  • Hrdina PD, Lapierre YD, Koranyi EK. Altered amitriptyline kinetics in a depressed patient with porto-caval anastomosis. Can J Psychiatry. 1985;30(2):111–113.
  • Farrall AJ, Wardlaw JM. Blood-brain barrier: ageing and microvascular disease - systematic review and meta-analysis. Neurobiol Aging. 2009;30(3):337–352.
  • Popescu BO, Toescu EC, Popescu LM, et al. Blood-brain barrier alterations in ageing and dementia. J Neurol Sci. 2009;283(1–2):99–106.
  • van de Waterbeemd H, Camenisch G, Folkers G, et al. Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors. J Drug Target. 1998;6(2):151–165.
  • Mehta DC, Short JL, Hilmer SN, et al. Drug access to the central nervous system in Alzheimer’s disease: preclinical and clinical insights. Pharm Res. 2015;32(3):819–839.
  • Eglen RM. Overview of muscarinic receptor subtypes. Handb Exp Pharmacol. 2012;208:3–28.
  • Volpicelli LA, Levey AI. Muscarinic acetylcholine receptor subtypes in cerebral cortex and hippocampus. Prog Brain Res. 2004;145:59–66.
  • Rang HP, Dale MM, Ritter JM, et al. Cholinergic transmission. In: Rang and Dale’s pharmacology. 6th ed. Edinburgh: Churchill Livingstone; 2007. p. 144–167.
  • Westfall TC, Westfall DP. Neurotransmission: the autonomic and somatic motor nervous systems. In: Goodman and Gilman’s the pharmacological basis of therapeutics. 11th ed. New York (NY): McGraw Hill; 2006. p. 137–181.
  • Brown JH, Taylor P. Muscarinic receptor agonists and antagonists. In: Goodman and Gilman’s the pharmacological basis of therapeutics. 11th ed. New York (NY): McGraw Hill; 2006. p. 183–216.
  • Voet D, Voet J. Biochemistry. New York (NY): John Wiley and Sons; 1995.
  • Čolović MB, Krstić DZ, Lazarević-Pašti TD, et al. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol. 2013;11(3):315–335.
  • Nilvebrant L. On the muscarinic receptors in the urinary bladder and the putative subclassification of muscarinic receptors. Acta Pharmacol Toxicol (Copenh). 1986;59 Suppl 1:1–45.
  • van Koppen CJ, Kaiser B. Regulation of muscarinic acetylcholine receptor signaling. Pharmacol Ther. 2003;98(2):197–220.
  • Zholos AV, Zholos AA, Bolton TB. G-protein-gated TRP-like cationic channel activated by muscarinic receptors: effect of potential on single-channel gating. J Gen Physiol. 2004;123(5):581–598.
  • Langmead CJ, Watson J, Reavill C. Muscarinic acetylcholine receptors as CNS drug targets. Pharmacol Ther. 2008;117(2):232–243.
  • Scarr E. Muscarinic receptors: their roles in disorders of the central nervous system and potential as therapeutic targets. CNS Neurosci Ther. 2012;18(5):369–379.
  • Wagg A. The cognitive burden of anticholinergics in the elderly – implications for the treatment of overactive bladder. Eur Urol Rev. 2012;7(1):42–49.
  • DeMaagd G, Geibig J. An overview of overactive bladder and its pharmacological management with a focus on anticholinergic drugs. P and T. 2006;31(8):462.
  • Andersson KE. Antimuscarinics for treatment of overactive bladder. Lancet Neurol. 2004;3(1):46–53.
  • Yamanishi T, Chapple CR, Yasuda K, et al. The role of M2 muscarinic receptor subtypes in mediating contraction of the pig bladder base after cyclic adenosine monophosphate elevation and/or selective M3 inactivation. J Urol. 2002;167(1):397–401.
  • Kay GG, Abou-Donia MB, Messer WS Jr, et al. Antimuscarinic drugs for overactive bladder and their potential effects on cognitive function in older patients. J Am Geriatr Soc. 2005;53(12):2195–2201.
  • Perry EK, Kilford L, Lees AJ, et al. Increased Alzheimer pathology in Parkinson’s disease related to antimuscarinic drugs. Ann Neurol. 2003;54(2):235–238.
  • Atkin PA, Veitch PC, Veitch EM, et al. The epidemiology of serious adverse drug reactions among the elderly. Drugs Aging. 1999;14(2):141–152.
  • Leon C, Gerretsen P, Uchida H, et al. Sensitivity to antipsychotic drugs in older adults. Curr Psychiatry Rep. 2010;12(1):28–33.
  • Narayan SW, Hilmer SN, Horsburgh S, et al. Anticholinergic component of the Drug Burden Index and the Anticholinergic Drug Scale as measures of anticholinergic exposure in older people in New Zealand: a population-level study. Drugs Aging. 2013;30(11):927–934.
  • 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):175–180.
  • Hilmer SN, McLachlan AJ, Le Couteur DG. Clinical pharmacology in the geriatric patient. Fundam Clin Pharmacol. 2007;21(3):217–230.
  • Sotaniemi EA, Arranto AJ, Pelkonen O, et al. Age and cytochrome P450-linked drug metabolism in humans: an analysis of 226 subjects with equal histopathologic conditions. Clin Pharmacol Ther. 1997;61(3):331–339.
  • Butler JM, Begg EJ. Free drug metabolic clearance in elderly people. Clin Pharmacokinet. 2008;47(5):297–321.
  • Mangoni AA, Jackson SHD. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2004;57(1):6–14.
  • Le Couteur DG, McLean AJ. The aging liver. Drug clearance and an oxygen diffusion barrier hypothesis. Clin Pharmacokinet. 1998;34(5):359–373.
  • Ruscin JM, Linnebur SA. Pharmacokinetics in the elderly. In The Merck manual for healthcare professionals. Kenilworth (NJ): Merck Sharp & Dohme Corp.; 2015.
  • Hilmer SN, Tran K, Rubie P, et al. Gentamicin pharmacokinetics in old age and frailty. Br J Clin Pharmacol. 2011;71(2):224–231.
  • Cho S, Lau SW, Tandon V, et al. Geriatric drug evaluation: where are we now and where should we be in the future? Arch Intern Med. 2011;171(10):937–940.
  • Ray PG, Meador KJ, Loring DW, et al. Central anticholinergic hypersensitivity in aging. J Geriatr Psychiatry Neurol. 1992;5(2):72–77.
  • Bowie MW, Slattum PW. Pharmacodynamics in older adults: a review. Am J Geriatr Pharmacother. 2007;5(3):263–303.
  • Duran CE, Azermai M, Vander Stichele RH. Systematic review of anticholinergic risk scales in older adults. Eur J Clin Pharmacol. 2013;69(7):1485–1496.
  • Tune L, Coyle JT. Serum levels of anticholinergic drugs in treatment of acute extrapyramidal side effects. Arch Gen Psychiatry. 1980;37(3):293–297.
  • Tune LE, Damlouji NF, Holland A, et al. Association of postoperative delirium with raised serum levels of anticholinergic drugs. Lancet. 1981;2(8248):651–653.
  • Tollefson GD, Montague-Clouse J, Lancaster SP. The relationship of serum anticholinergic activity to mental status performance in an elderly nursing home population. J Neuropsychiatry Clin Neurosci. 1991;3(3):314–319.
  • Carnahan RM, Lund BC, Perry PJ, et al. A critical appraisal of the utility of the serum anticholinergic activity assay in research and clinical practice. Psychopharmacol Bull. 2002;36(2):24–39.
  • Starr JM, Farrall AJ, Armitage P, et al. Blood-brain barrier permeability in Alzheimer’s disease: a case-control MRI study. Psychiatry Res. 2009;171(3):232–241.
  • 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):1481–1486.
  • Vinogradov S, Fisher M, Warm H, et al. The cognitive cost of anticholinergic burden: decreased response to cognitive training in schizophrenia. Am J Psychiatry. 2009;166(9):1055–1062.
  • Brecht S, Reiff J, Vock U, et al. Serum anticholinergic activity in patients following cardiac surgery and healthy individuals following amitriptyline application. Methods Find Exp Clin Pharmacol. 2007;29(3):223–230.
  • Cox EA, Kwatra SG, Shetty S, et al. Flaws in the serum anticholinergic activity assay: implications for the study of delirium. J Am Geriatr Soc. 2009;57(9):1707–1708.
  • Plaschke K, Thomas C, Engelhardt R, et al. Significant correlation between plasma and CSF anticholinergic activity in presurgical patients. Neurosci Lett. 2007;417(1):16–20.
  • Collamati A, Martone AM, Poscia A, et al. Anticholinergic drugs and negative outcomes in the older population: from biological plausibility to clinical evidence. Aging Clin Exp Res. 2016;28(1):25–35.
  • Mangoni AA, Munster BCV, 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):785–793.
  • Boustani M, Baker MS, Campbell N, et al. Impact and recognition of cognitive impairment among hospitalized elders. J Hosp Med. 2010;5(2):69–75.
  • 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):173–178.
  • Salahudeen MS, Duffull SB, Nishtala PS. Impact of anticholinergic discontinuation on cognitive outcomes in older people: a systematic review. Drugs Aging. 2014;31(3):185–192.
  • Kouladjian L, Gnjidic D, Chen TF, et al. Development, validation and evaluation of an electronic pharmacological tool: the Drug Burden Index Calculator©. Res Social Adm Pharm. 2015; pii: S1551-7411(15)00260-0. [Epub ahead of print]
  • Kouladjian L, Gnjidic D, Chen TF, et al. Drug Burden Index in older adults: theoretical and practical issues. Clin Interv Aging. 2014;9:1503–1515.
  • Nishtala PS, McLachlan AJ, Bell JS, et al. Determinants of antipsychotic medication use among older people living in aged care homes in Australia. Int J Geriatr Psychiatry. 2010;25(5):449–457.
  • 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):336–341.
  • 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):654–659.
  • 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):103–112.
  • Ruxton K, Woodman RJ, Mangoni AA. Drugs with anticholinergic effects and cognitive impairment, falls and all-cause mortality in older adults: a systematic review and meta-analysis. Br J Clin Pharmacol. 2015;80(2):209–220.
  • Boustani M, Schubert C, Sennour Y. The challenge of supporting care for dementia in primary care. Clin Interv Aging. 2007;2(4):631–636.
  • Mintzer J, Burns A. Anticholinergic side-effects of drugs in elderly people. J R Soc Med. 2000;93(9):457–462.
  • Best O, Gnjidic D, Hilmer SN, et al. Investigating polypharmacy and drug burden index in hospitalised older people. Intern Med J. 2013;43(8):912–918.
  • Margallo-Lana M, Swann A, O’Brien J, et al. Prevalence and pharmacological management of behavioural and psychological symptoms amongst dementia sufferers living in care environments. Int J Geriatr Psychiatry. 2001;16(1):39–44.
  • Angelini A, Bendini C, Neviani F, et al. Behavioral and psychological symptoms of dementia (BPSD) in elderly demented subjects: is the long lasting use of atypical antipsychotic drugs useful and safe? Arch Gerontol Geriatr. 2007;44 Suppl 1:35–43.
  • Azermai M. Dealing with behavioral and psychological symptoms of dementia: a general overview. Psychol Res Behav Manag. 2015;8:181–185.
  • Declercq T, Petrovic M, Azermai M, et al. Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and psychological symptoms in older people with dementia. Cochrane Database Syst Rev. 2013;3:Cd007726.
  • Azermai M, Petrovic M, Engelborghs S, et al. The effects of abrupt antipsychotic discontinuation in cognitively impaired older persons: a pilot study. Aging Ment Health. 2013;17(1):125–132.
  • Ballard C, Hanney ML, Theodoulou M, et al. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Lancet Neurol. 2009;8(2):151–157.
  • Landi F, Russo A, Liperoti R, et al. Anticholinergic drugs and physical function among frail elderly population. Clin Pharmacol Ther. 2007;81(2):235–241.
  • 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):1584–1591.
  • 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):251–257.
  • Boyle N, Naganathan V, Cumming RG. Medication and falls: risk and optimization. Clin Geriatr Med. 2010;26(4):583–605.
  • Golden AG, Ma Q, Nair V, et al. Risk for fractures with centrally acting muscle relaxants: an analysis of a national Medicare Advantage claims database. Ann Pharmacother. 2010;44(9):1369–1375.
  • 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):307–310.
  • 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):875–880.
  • Nebes RD, Pollock BG, Halligan EM, et al. Serum anticholinergic activity and motor performance in elderly persons. J Gerontol A Biol Sci Med Sci. 2007;62A(1):83–85.
  • Huang AR, Mallet L, Rochefort CM, et al. Medication-related falls in the elderly: causative factors and preventive strategies. Drugs Aging. 2012;29(5):359–376.
  • 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):753–758.
  • Salahudeen MS, Hilmer SN, Nishtala PS. Comparison of anticholinergic risk scales and associations with adverse health outcomes in older people. J Am Geriatr Soc. 2015;63(1):85–90.
  • 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.
  • 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):565–572.
  • 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):155–161.
  • Lonnroos E, Gnjidic D, Hilmer SN, et al. Drug Burden Index and hospitalization among community-dwelling older people. Drugs Aging. 2012;29(5):395–404.
  • 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):256–263.
  • Panula J, Puustinen J, Jaatinen P, et al. Effects of potent anticholinergics, sedatives and antipsychotics on postoperative mortality in elderly patients with hip fracture: a retrospective, population-based study. Drugs Aging. 2009;26(11):963–971.
  • Ogino S, Miyamoto S, Tenjin T, et al. Effects of discontinuation of long-term biperiden use on cognitive function and quality of life in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(1):78–83.
  • Baker LA, Cheng LY, Amara IB. The withdrawal of benztropine mesylate in chronic schizophrenic patients. Br J Psychiatry. 1983;143:584–590.
  • Huizer-Pajkos A, Kane AE, Howlett SE, et al. Adverse geriatric outcomes secondary to polypharmacy in a mouse model: the influence of aging. J Gerontol A Biol Sci Med Sci. 2015;pii: glv046. [Epub ahead of print].
  • Bell JS, Mezrani C, Blacker N, et al. Anticholinergic and sedative medicines - prescribing considerations for people with dementia. Aust Fam Physician. 2012;41(1–2):45–49.
  • Cancelli I, Beltrame M, Gigli GL, et al. Drugs with anticholinergic properties: cognitive and neuropsychiatric side-effects in elderly patients. Neurol Sci. 2009;30(2):87–92.
  • Pharmaceutical Society of Australia. Australian medicines handbook [Internet]. Adelaide: Australian Medicines Handbook; 2015 January [cited 2015 Nov 24]. Available from: http://amhonline.amh.net.au/
  • By the American Geriatrics Society Beers Criteria Update Expert P. American Geriatrics Society 2015 updated beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227–2246.
  • Hanlon JT, Semla TP, Schmader KE. Alternative medications for medications in the use of high-risk medications in the elderly and potentially harmful drug–disease interactions in the elderly quality measures. J Am Geriatr Soc. 2015;63(12):e8–e18.
  • Tomida K, Takahashi N, Saito S, et al. Relationship of psychopathological symptoms and cognitive function to subjective quality of life in patients with chronic schizophrenia. Psychiatry Clin Neurosci. 2010;64(1):62–69.

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