Skip to main content
Top
Published in: Drugs & Aging 1/2018

01-01-2018 | Systematic Review

Brain Over Bladder: A Systematic Review of Dual Cholinesterase Inhibitor and Urinary Anticholinergic Use

Authors: Laura K. Triantafylidis, Jenna S. Clemons, Emily P. Peron, John Roefaro, Kristin M. Zimmerman

Published in: Drugs & Aging | Issue 1/2018

Login to get access

Abstract

Background

Case reports have demonstrated that dual use of cholinesterase inhibitors (ChIs) and urinary anticholinergics (UAChs) in older adults may be associated with delusions, aggression, changes in cognition, and anxiety, which typically resolve on drug discontinuation. Despite opposing mechanisms of action, these drugs continue to be co-prescribed.

Objective

This systematic review evaluates cognitive and functional outcomes of dual use of ChIs and UAChs and describes its prevalence.

Patients and Methods

A literature search using terms related to ChIs and UAChs was conducted. Observational or interventional studies evaluating cognitive or functional outcomes in subjects receiving dual therapy were included for the primary aim. Articles describing prevalence of dual use were included for the secondary aim.

Results

Of 1340 unique results, five studies met the inclusion criteria for the primary aim. Four of the studies assessed cognitive outcomes—three failed to identify a significant difference in cognitive function with dual use and the fourth study observed a statistically significant improvement in cognition with dual use of high-dose donepezil and solifenacin when compared with baseline. Three studies assessed functional outcomes—one revealed a 50% greater quarterly decline in activities of daily living (p = 0.01) among dual users functioning in the top quartile, another revealed significant functional improvement in dual users, and the final study did not demonstrate a significant difference. Seventeen articles were included for the secondary aim. Prevalence of dual use ranged from 1.2 to 40.5%.

Conclusion

This systematic review revealed a high prevalence of dual use of ChIs and UAChs; however, there are mixed results for cognitive and functional outcomes. Results were limited by methodological flaws. Observational or interventional studies assessing dual users are lacking and further study of cognitive and functional risks of dual ChI and UACh use is needed.
Literature
1.
go back to reference Orme S, Morris V, Gibson W, Wagg A. Managing urinary incontinence in patients with dementia: pharmacologic treatment options and considerations. Drugs Aging. 2015;32(7):559–67.CrossRefPubMed Orme S, Morris V, Gibson W, Wagg A. Managing urinary incontinence in patients with dementia: pharmacologic treatment options and considerations. Drugs Aging. 2015;32(7):559–67.CrossRefPubMed
2.
go back to reference Averbeck MA, Ataweel W, Manu-Marin A, Madersbacher H. Management of LUTS in patients with dementia and associated disorders. Neurol Urodyn. 2017;36:245–52.CrossRef Averbeck MA, Ataweel W, Manu-Marin A, Madersbacher H. Management of LUTS in patients with dementia and associated disorders. Neurol Urodyn. 2017;36:245–52.CrossRef
3.
go back to reference Star JM. Cholinesterase inhibitor treatment and urinary incontinence in Alzheimer’s disease. J Am Geriatr Soc. 2007;55(5):800–1.CrossRef Star JM. Cholinesterase inhibitor treatment and urinary incontinence in Alzheimer’s disease. J Am Geriatr Soc. 2007;55(5):800–1.CrossRef
4.
go back to reference Hashimoto M, Imamura T, Tanimukai S, Kazui H, Mori E. Urinary incontinence: an unrecognized adverse effect with donepezil. Lancet. 2000;356:568.CrossRefPubMed Hashimoto M, Imamura T, Tanimukai S, Kazui H, Mori E. Urinary incontinence: an unrecognized adverse effect with donepezil. Lancet. 2000;356:568.CrossRefPubMed
5.
go back to reference Edwards KR, O’Connor JT. Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors. J Am Geriatr Soc. 2002;50(6):1165–6.CrossRefPubMed Edwards KR, O’Connor JT. Risk of delirium with concomitant use of tolterodine and acetylcholinesterase inhibitors. J Am Geriatr Soc. 2002;50(6):1165–6.CrossRefPubMed
6.
go back to reference Higgins JPT, Green S (eds). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011. www.handbook.cochrane.org. Accessed 10 Jan 2018. Higgins JPT, Green S (eds). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011. www.​handbook.​cochrane.​org. Accessed 10 Jan 2018.
7.
go back to reference Sink KM, Thomas J, Xu H, et al. Dual use of bladder anticholinergics and cholinesterase inhibitors: long-term functional and cognitive outcomes. J Am Geriatr Soc. 2008;56(5):847–53.CrossRefPubMedPubMedCentral Sink KM, Thomas J, Xu H, et al. Dual use of bladder anticholinergics and cholinesterase inhibitors: long-term functional and cognitive outcomes. J Am Geriatr Soc. 2008;56(5):847–53.CrossRefPubMedPubMedCentral
8.
go back to reference Isik AT, Celik T, Bozoglu E, Doruk H. Trospium and cognition in patients with late onset Alzheimer disease. J Nutr Health Aging. 2009;13(8):672–6.CrossRefPubMed Isik AT, Celik T, Bozoglu E, Doruk H. Trospium and cognition in patients with late onset Alzheimer disease. J Nutr Health Aging. 2009;13(8):672–6.CrossRefPubMed
9.
go back to reference Sakakibara R, Ogata T, Uchiyama T, et al. How to manage overactive bladder in elderly individuals with dementia? a combined use of Donepezil, a central acetylcholinesterase inhibitor, and propiverine, a peripheral muscarine receptor antagonist. J Am Geriatri Soc. 2009;57(8):1515–7.CrossRef Sakakibara R, Ogata T, Uchiyama T, et al. How to manage overactive bladder in elderly individuals with dementia? a combined use of Donepezil, a central acetylcholinesterase inhibitor, and propiverine, a peripheral muscarine receptor antagonist. J Am Geriatri Soc. 2009;57(8):1515–7.CrossRef
10.
go back to reference Boudreau DM, Yu O, Gray SL, et al. Concomitant use of cholinesterase inhibitors and anticholinergics: prevalence and outcomes. J Am Geriatr Soc. 2011;59(11):2069–76.CrossRefPubMed Boudreau DM, Yu O, Gray SL, et al. Concomitant use of cholinesterase inhibitors and anticholinergics: prevalence and outcomes. J Am Geriatr Soc. 2011;59(11):2069–76.CrossRefPubMed
11.
go back to reference Chase TN, Farlow MR, Clarence-Smith K. Donepezil Plus Solifenacin (CPC-201) treatment for Alzheimer’s disease. Neurotherapeutics. 2017;15:405–16.CrossRef Chase TN, Farlow MR, Clarence-Smith K. Donepezil Plus Solifenacin (CPC-201) treatment for Alzheimer’s disease. Neurotherapeutics. 2017;15:405–16.CrossRef
12.
go back to reference Roe CM, Anderson MJ, Spivack B. Use of anticholinergic medications by older adults with dementia. J Am Geriatr Soc. 2002;50(5):836–42.CrossRefPubMed Roe CM, Anderson MJ, Spivack B. Use of anticholinergic medications by older adults with dementia. J Am Geriatr Soc. 2002;50(5):836–42.CrossRefPubMed
13.
go back to reference Carnahan RM, Lund BC, Perry PJ, Chrischilles EA. The concurrent use of anticholinergics and cholinesterase inhibitors: rare event or common practice? J Am Geriatr Soc. 2004;52(12):2082–7.CrossRefPubMed Carnahan RM, Lund BC, Perry PJ, Chrischilles EA. The concurrent use of anticholinergics and cholinesterase inhibitors: rare event or common practice? J Am Geriatr Soc. 2004;52(12):2082–7.CrossRefPubMed
14.
go back to reference Gill SS, Mamdani M, Naglie G, et al. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Arch Intern Med. 2005;165:808–13.CrossRefPubMed Gill SS, Mamdani M, Naglie G, et al. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Arch Intern Med. 2005;165:808–13.CrossRefPubMed
15.
go back to reference Modi A, Weiner M, Craig BA, et al. Concomitant use of anticholinergics with acetylcholinesterase inhibitors in medicaid recipients with dementia and residing in nursing homes. J Am Geriatr Soc. 2009;57(7):1238–44.CrossRefPubMed Modi A, Weiner M, Craig BA, et al. Concomitant use of anticholinergics with acetylcholinesterase inhibitors in medicaid recipients with dementia and residing in nursing homes. J Am Geriatr Soc. 2009;57(7):1238–44.CrossRefPubMed
16.
go back to reference Robinson M, Rowett D, Leverton A, Mabbott V. Changes in utilisation of anticholinergic drugs after initiation of cholinesterase inhibitors. Pharmacoepidemiol Drug Saf. 2009;18:659–64.CrossRefPubMed Robinson M, Rowett D, Leverton A, Mabbott V. Changes in utilisation of anticholinergic drugs after initiation of cholinesterase inhibitors. Pharmacoepidemiol Drug Saf. 2009;18:659–64.CrossRefPubMed
17.
go back to reference Efjestad AS, Molden E, Oksengard AR. Pharmacist-initiated management of antagonistic interactions between anticholinergic drugs and acetyl cholinesterase inhibitors in individuals with dementia. J Am Geriatr Soc. 2013;61(9):1624–5.CrossRefPubMed Efjestad AS, Molden E, Oksengard AR. Pharmacist-initiated management of antagonistic interactions between anticholinergic drugs and acetyl cholinesterase inhibitors in individuals with dementia. J Am Geriatr Soc. 2013;61(9):1624–5.CrossRefPubMed
18.
go back to reference Torvinen-Kiiskinen S, Taipale H, Tanskanen A, et al. Concomitant use of acetylcholine esterase inhibitors and urinary antispasmodics among finish community-dwelling persons with Alzheimer disease. J Clin Psychopharmacol. 2014;34(6):722–7.CrossRefPubMed Torvinen-Kiiskinen S, Taipale H, Tanskanen A, et al. Concomitant use of acetylcholine esterase inhibitors and urinary antispasmodics among finish community-dwelling persons with Alzheimer disease. J Clin Psychopharmacol. 2014;34(6):722–7.CrossRefPubMed
19.
go back to reference Prescire Editorial Staff. Alzheimer’s disease in France: too many patients exposed to drug interactions involving cholinesterase inhibitors. Prescrire Int. 2014;23(150):156. Prescire Editorial Staff. Alzheimer’s disease in France: too many patients exposed to drug interactions involving cholinesterase inhibitors. Prescrire Int. 2014;23(150):156.
20.
go back to reference Escolano Pueyo A, Casajus Lagranja P, Arrieta Navarro R, et al. Concomitant use of drugs with anticholinergic effects and acetylcholinesterase inhibitors in elderly people with cognitive impairment in a nursing home. Eur J Hosp Pharm. 2016;23(1):262. Escolano Pueyo A, Casajus Lagranja P, Arrieta Navarro R, et al. Concomitant use of drugs with anticholinergic effects and acetylcholinesterase inhibitors in elderly people with cognitive impairment in a nursing home. Eur J Hosp Pharm. 2016;23(1):262.
21.
go back to reference Lampela P, Taipale H, Hartikainen S. Use of cholinesterase inhibitors increases initiation of urinary anticholinergics in persons with alzheimer’s disease. Am J Geriatr Soc. 2016;64(7):1510–2.CrossRef Lampela P, Taipale H, Hartikainen S. Use of cholinesterase inhibitors increases initiation of urinary anticholinergics in persons with alzheimer’s disease. Am J Geriatr Soc. 2016;64(7):1510–2.CrossRef
22.
go back to reference Efjestad AS, Ihle-Hansen H, Hjellvik V, Salvesen H. Comedication and treatment length in users of acetylcholinesterase inhibitors. Dement Geriatr Cogn Disord Extra. 2017;7:30–40.CrossRef Efjestad AS, Ihle-Hansen H, Hjellvik V, Salvesen H. Comedication and treatment length in users of acetylcholinesterase inhibitors. Dement Geriatr Cogn Disord Extra. 2017;7:30–40.CrossRef
23.
go back to reference Reppas-Rindlisbacher CE, Fischer HD, Fung K, et al. Anticholinergic drug burden in persons with dementia taking a cholinesterase inhibitor: the effect of multiple physicians. J Am Geriatr Soc. 2016;64(3):492–500.CrossRefPubMedPubMedCentral Reppas-Rindlisbacher CE, Fischer HD, Fung K, et al. Anticholinergic drug burden in persons with dementia taking a cholinesterase inhibitor: the effect of multiple physicians. J Am Geriatr Soc. 2016;64(3):492–500.CrossRefPubMedPubMedCentral
24.
go back to reference Zarowitz BJ, Allen C, O’Shea T, et al. Challenges in the pharmacological management of nursing home residents with overactive bladder or urinary incontinence. J Am Geriatr Soc. 2015;63(11):2298–307.CrossRefPubMed Zarowitz BJ, Allen C, O’Shea T, et al. Challenges in the pharmacological management of nursing home residents with overactive bladder or urinary incontinence. J Am Geriatr Soc. 2015;63(11):2298–307.CrossRefPubMed
25.
go back to reference Ng DB, McCart M, Klein C, et al. Evaluating outcomes in patients with overactive bladder within an integrated healthcare delivery system using treatment patterns analyzer. Am Health Drug Benefits. 2016;9(6):343–53.PubMedPubMedCentral Ng DB, McCart M, Klein C, et al. Evaluating outcomes in patients with overactive bladder within an integrated healthcare delivery system using treatment patterns analyzer. Am Health Drug Benefits. 2016;9(6):343–53.PubMedPubMedCentral
26.
go back to reference Green AR, Segal J, Tian J, et al. Use of bladder antimuscarinics in older adults with impaired cognition. J Am Geriatri Soc. 2017;65(2):390–4.CrossRef Green AR, Segal J, Tian J, et al. Use of bladder antimuscarinics in older adults with impaired cognition. J Am Geriatri Soc. 2017;65(2):390–4.CrossRef
27.
go back to reference Glavind K, Chancellor M. Antimuscarinics for the treatment of overactive bladder: understanding the role of muscarinic subtype selectivity. Int Urogynecol J. 2011;22:907–17.CrossRefPubMed Glavind K, Chancellor M. Antimuscarinics for the treatment of overactive bladder: understanding the role of muscarinic subtype selectivity. Int Urogynecol J. 2011;22:907–17.CrossRefPubMed
28.
go back to reference Oelke M, Becher K, Castro-Diaz D, et al. Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international concensus validation process (LUTS-FORTA 2014). Age Aging. 2015;44:745–55.CrossRef Oelke M, Becher K, Castro-Diaz D, et al. Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international concensus validation process (LUTS-FORTA 2014). Age Aging. 2015;44:745–55.CrossRef
29.
go back to reference Siegler EL, Reidenberg M. Treatment of urinary incontinence with anticholinergics in patients taking cholinesterase inhibitors for dementia. Clin Pharmacol Ther. 2004;75(5):484–8.CrossRefPubMed Siegler EL, Reidenberg M. Treatment of urinary incontinence with anticholinergics in patients taking cholinesterase inhibitors for dementia. Clin Pharmacol Ther. 2004;75(5):484–8.CrossRefPubMed
Metadata
Title
Brain Over Bladder: A Systematic Review of Dual Cholinesterase Inhibitor and Urinary Anticholinergic Use
Authors
Laura K. Triantafylidis
Jenna S. Clemons
Emily P. Peron
John Roefaro
Kristin M. Zimmerman
Publication date
01-01-2018
Publisher
Springer International Publishing
Published in
Drugs & Aging / Issue 1/2018
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI
https://doi.org/10.1007/s40266-017-0510-6

Other articles of this Issue 1/2018

Drugs & Aging 1/2018 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.