Abstract
Objectives
For persons with dementia, the appropriate duration of cholinesterase inhibitor (ChEI)
use remains unclear. We examined patterns of ChEI use during nursing home (NH) transition
and the factors associated with discontinuation following admission.
Design
Population-based retrospective cohort study using linked health administrative and
Resident Assessment Instrument Minimum Dataset, version 2.0 databases.
Setting and participants
A total of 47,851 older adults (mean age = 84.8 years, standard deviation = 6.8) with
dementia newly admitted to a NH in Ontario, Canada between 2011 and 2015.
Measurements
ChEI use at admission and during the following year was identified from prescription
claims. Resident sociodemographic and health characteristics at admission, including
a 72-item frailty index, were derived from the Resident Assessment Instrument Minimum
Dataset 2.0. Additional resident and prescriber characteristics were derived from
administrative data. Discontinuation was defined as a 30+-day gap in ChEI supply.
Multivariable subdistribution hazard models were used to estimate the independent
effect of resident frailty and other factors on ChEI discontinuation.
Results
Approximately one-third (17,560) of residents with dementia were on a ChEI at admission.
Among this group, 17.7% (3110) discontinued use over follow-up. Incidence of discontinuation
was significantly higher among residents with syncope [subdistribution hazard ratio,
sHR = 2.21, 95% confidence interval, CI (1.52, 3.22)], more severe behavioral symptoms
[sHR = 1.79, 95% CI (1.57, 2.05)], cognitive impairment [sHR = 1.26, 95% CI (1.07,
1.48)], higher frailty, [sHR = 1.19, 95% CI (1.04, 1.36)], and a primary prescriber
active in the NH [sHR = 1.28, 95% CI (1.14, 1.45)]. A significantly lower incidence
was observed for older and unmarried residents and those with a longer duration of
use.
Conclusions/Implications
Less than one-fifth of residents on a ChEI at admission discontinued use during the
following year. Although some of the predictors of discontinuation align with past
research and current clinical recommendations, others were unexpected and point to
novel drivers of ChEI use. Future investigations should explore the varied reasons
underlying these associations and resident outcomes associated with ChEI discontinuation.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the American Medical Directors AssociationAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Pharmacological recommendations for the symptomatic treatment of dementia: The Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012.Alzheimer Res Ther. 2013; 5: S5
- Mental health-related drug utilization among older adults: Prevalence, trends, and costs.Am J Geriatr Psychiatry. 2005; 13: 892-900
- Ten years of cholinesterase inhibitors.Int J Geriatr Psychiatry. 2009; 24: 437-442
- Cholinesterase inhibitor use in U.S. nursing homes: Results from the National Nursing Home Survey.J Am Geriatr Soc. 2009; 57: 2269-2274
- Cholinesterase inhibitor and memantine use in newly admitted nursing home residents with dementia.J Am Geriatr Soc. 2011; 59: 1253-1259
- Patterns and determinants of dementia pharmacotherapy in a population-based cohort of home care clients.Drugs Aging. 2013; 30: 569-585
- Dementia diagnosis, treatment, and care in specialist clinics in two Scandinavian countries: A data comparison between the Swedish Dementia Registry (SveDem) and the Danish Dementia Registry.J Alzheimer Dis. 2015; 48: 229-239
- Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimers disease: A systematic review and meta-analysis.Clin Intervent Aging. 2008; 3: 211-225
- A Risk-benefit assessment of dementia medications: Systematic review of the evidence.Drugs Aging. 2015; 32: 453-467
- Long-term efficacy and toxicity of cholinesterase inhibitors in the treatment of Alzheimer disease.Can J Psychiatry. 2014; 59: 618-623
- Adverse effects of cholinesterase inhibitors in dementia, according to the pharmacovigilance databases of the United-States and Canada.PLoS One. 2015; 10: e0144337
- The tolerability and safety of cholinesterase inhibitors in the treatment of dementia.Int J Clin Pract. 2002; 56: 45-63
- Syncope and its consequences in patients with dementia receiving cholinesterase inhibitors: A population-based cohort study.Arch Intern Med. 2009; 169: 867-873
- A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs.Arch Intern Med. 2005; 165: 808-813
- Drug interactions with cholinesterase inhibitors.Drug Safety. 2007; 30: 1063-1071
- A systematic review of practice guidelines and recommendations for discontinuation of cholinesterase inhibitors in dementia.Am J Geriatr Psychiatry. 2018; 26: 134-147
- Cholinesterase inhibitor discontinuation: The buck stops here.Am J Geriatr Psychiatry. 2018; 26: 148-149
- Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia.Can Fam Phys. 2014; 60: 433
- A population-based study of cholinesterase inhibitor use for dementia.J Am Geriatr Soc. 2007; 55: 1517-1523
- Patterns of cholinesterase-inhibitor use in the nursing home setting: A retrospective analysis.Am J Geriatr Pharmacother. 2006; 4: 154-160
- Donepezil use in US nursing homes.Aging Clin Exp Res. 2004; 16: 60-67
- Persistence with cholinesterase inhibitor therapy in a population-based cohort of patients with Alzheimer's disease.Pharmacoepidemiol Drug Safety. 2010; 19: 670-679
- Tolerability of cholinesterase inhibitors: A population-based study of persistence, adherence, and switching.Drugs Aging. 2017; 34: 221-231
- Persistence with cholinesterase inhibitor therapy for dementia.Drugs Aging. 2009; 26: 403-407
- Persistence and adherence with dementia pharmacotherapy: Relevance of patient, provider, and system factors.Can J Psychiatry. 2014; 59: 624-631
- An evaluation of data quality in Canada's Continuing Care Reporting System (CCRS): Secondary analyses of Ontario data submitted between 1996 and 2011.BMC Med Inform Dec Making. 2013; 13: 27
- Identification of physician-diagnosed Alzheimers disease and related dementias in population-based administrative data: A validation study using family physicians electronic medical records.J Alzheimer Dis. 2016; 54: 337-349
- . Ontario Public Drug Programs: Limited Use Drug Products. Ontario Ministry of Health and Long-Term Care (online).(Available at:)https://www.formulary.health.gov.on.ca/formulary/limitedUseNotes.xhtml?pcg9Id=120400018Date accessed: March 21, 2018
- New Eligibility Requirements for The Low-Income Seniors Co-Payment Drug Program. Ontario Ministry of Health and Long-Term Care (online).(Available at:)http://www.health.gov.on.ca/en/public/programs/drugs/programs/copayment/copayment.aspxDate accessed: April 12, 2018
- The prevalence and health consequences of frailty in a population-based older home care cohort: A comparison of different measures.BMC Geriatr. 2016; 16: 133
- Frailty and potentially inappropriate medication use at nursing home transition.J Am Geriatr Soc. 2017; 65: 2205-2212
- MDS cognitive performance scale.J Gerontol. 1994; 49: M174-M182
- The aggressive behavior scale: A new scale to measure aggression based on the minimum data set.J Am Geriatr Soc. 2008; 56: 2298-2303
- Practical recommendations for reporting Fine-Gray model analyses for competing risk data.Statistics Med. 2017; 36: 4391-4400
- Treatment of dementia in community-dwelling and institutionalized Medicare beneficiaries.J Am Geriatr Soc. 2007; 55: 1508-1516
- Antidementia drug use among community-dwelling individuals with Alzheimers disease in Finland: A nationwide register-based study.Int Clin Psychopharmacol. 2014; 29: 216-223
- Discontinuation of cholinesterase inhibitor treatment and determinants thereof in The Netherlands.Drugs Aging. 2010; 27: 663-675
- Cholinesterase inhibitor utilization: The impact of provincial drug policy on discontinuation.Value Health. 2016; 19: 688-696
- Predictors of long-term care placement in persons with dementia: A systematic review and meta−analysis.Int J Geriatr Psychiatry. 2016; 31: 1151-1171
- Discontinuing cholinesterase inhibitors: Results of a survey of Canadian dementia experts.Int Psychogeriatr. 2011; 23: 539-545
- How to treat the frail elderly: The challenge of multimorbidity and polypharmacy.Can Urol Assoc J. 2013; 7: S183
- Role of donepezil in the management of neuropsychiatric symptoms in Alzheimer's disease and dementia with Lewy bodies.CNS Neurosci Therapeut. 2016; 22: 159-166
- Cholinesterase inhibitor discontinuation in patients with Alzheimer's disease: A meta-analysis of randomized controlled trials.J Clin Psychiatry. 2015; 76: e1424-e1431
- A randomized placebo-controlled discontinuation study of cholinesterase inhibitors in institutionalized patients with moderate to severe Alzheimer disease.J Am Med Dir Assoc. 2016; 17: 142-147
- Product Monograph: Aricept (donepezil hydrochloride) cholinesterase inhibitor. Pfizer Canada (online).(Available at:)https://www.pfizer.ca/sites/g/files/g10037206/f/201612/ARICEPT_PM_E_177353_18Dec2014_R.pdfDate accessed: March 28, 2018
Article info
Publication history
Published online: September 24, 2018
Footnotes
This research was funded in part by the Canadian Frailty Network grant SIG2014-M1 (known previously as Technology Evaluation in the Elderly Network, TVN), supported by the Government of Canada through Networks of Centers of Excellence (NCE) Program, and also the Canadian Institutes of Health Research (CIHR) through operating grant MOP-136854. This study was also supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results and conclusions reported are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Parts of this material are based on data and information compiled and provided by the Canadian Institute for Health Information (CIHI). However, the analyses, conclusions, opinions, and statements expressed herein are those of the author, and not necessarily those of CIHI. We thank IMS Brogan Inc. for use of their Drug Information Database.
The Sunnybrook Health Sciences Center Research Ethics Board approved this study, which was conducted according to the rigorous privacy and confidentiality safeguards at ICES.
All authors meet the criteria for authorship stated in the Uniform Requirements for Manuscripts Submitted to Biomedical Journals.
The study sponsors provided the operating costs and infrastructure to support the research. No funding bodies had any role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.
The authors declare no conflicts of interest.
Identification
Copyright
© 2018 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
