Deprescribing ChEI in LTC residents with progressive dementia

Contributed by: Ayah Matar, MD, CCFP, COE - View bio

Case

Mrs. Farley is an 84-year-old living in long-term care. She has a known major neurocognitive disorder secondary to Alzheimer’s Disease and has been on Donepezil 10mg daily for the past eight years. She needs cueing and assistance for most of her basic activities of daily living including washing, dressing and bathing. Her most recent Mini Mental State Examination score was 8/30. Her son would like to have her cholinesterase inhibitor (ChEI) discontinued to reduce pill burden.

Issue

What is the evidence regarding the deprescription of cholinesterase inhibitors in older patients with progressive dementia residing in nursing home?

Background

A study in 2018 showed that approximately one third of the 47,851 older adults with dementia newly admitted to a nursing home in Ontario, Canada between 2011 and 2015 were on a cholinesterase inhibitor.¹ It is important to note that ChEI use has been associated with increased risk of nausea, vomiting, weight loss, syncope and bradycardia; all of which may be cause for concern particularly in a frail elderly patient.²

Evidence

Recent evidence-based clinical practice guidelines for deprescribing cholinesterase inhibitors recommended a trial of discontinuation if cognition has significantly worsened over the past six months; no benefit was seen any time during treatment; or the individual has severe dementia.³ It is important to note that these recommendations had low or very low-quality evidence due to high risk of bias and lack of generalizability. A systematic review published in 2020 on deprescribing ChEI suggested that discontinuing it may result in worse cognitive, neuropsychiatric and functional status although not supported by high certainty evidence.⁴ Only one of the randomized controlled trials (RTC) included in this review specifically studied individuals residing in long-term care.⁵ The results of that trial suggested that ChEI discontinuation is safe and well tolerated in most patients residing in long-term care although it was limited by a small sample size (N=40).⁵ They did find, however, that the presence of hallucinations or delusions at baseline, prior to medication initiation, may predict deterioration after deprescribing. Deprescribing must be balanced with the risk of worsening cognition, neuropsychological symptoms and function which may not be regained with restarting the medication.

A potential barrier for deprescribing ChEI is the risk that patients may have behavioural and psychological symptoms re-emerge and require subsequent exposure to high-risk medications such as antipsychotics. A retrospective study from 2020 evaluated the impact of deprescribing ChEIs on subsequent aggressive behaviours and incident antipsychotic prescribing in a large, national sample of nursing home residents with severe dementia.⁶ The study found that deprescribing was not associated with a significant increase in aggressive behaviors and was associated with a reduced likelihood for receiving new prescriptions for antipsychotics.⁶

How to deprescribe 

• Donepezil should be decreased to 5mg daily for a month then discontinued.
• Galantamine should be reduced to 8mg from 16mg daily for two weeks to one month then discontinued.
• Rivastigmine should be reduced to 3mg bid from 4.5mg bid for two weeks, then 1.5mg bid for two weeks then discontinued.

A return of symptoms should prompt resumption of the prior dose. There is not good evidence for this, but this is a reverse of the initiation titration.

Recommendation

In making decisions about discontinuing ChEI in institutionalized patients residing in long-term care, clinicians should exercise caution and consider factors important to patients and their caregivers. Factors may include reduction in pill burden, side effects, cost versus potential decrease in cognition, function or increased neuropsychological symptoms.

Back to our case

Our patient resides in long-term care, requires assistance with most of her basic activities of daily living and her son requested a trial of deprescription of ChEI to reduce pill burden. A slow taper to 5mg daily for one month then discontinuation can be initiated with caution and close monitoring of possible withdrawal symptoms such as agitation, aggression, hallucinations or reduced consciousness in the first week. The taper is slow with changes made only every two to four weeks. In this case, it is recommended to re-start the previous dose immediately. In this patient’s case that would be donepezil 10mg daily.³ A follow-up should be arranged to assess for worsening cognition, function or behavioural or psychological symptoms in the first six weeks following the dose reduction or discontinuation in order to assess the success for the taper.³ As in all cases of tapering of medications, written instructions should be provided to patients describing the tapering schedule, symptoms to watch for and who to contact if symptoms or questions arise.

Reference

1. Maclagan LC, Bronskill SE, Guan J, Campitelli MA, Herrmann N, Lapane KL, Hogan DB, Amuah JE, Seitz DP, Gill SS, Maxwell CJ. Predictors of cholinesterase discontinuation during the first year after nursing home admission. Journal of the American Medical Directors Association. 2018 Nov 1;19(11):959-66.
2. Jordana O, Lanctot KL, Mazereeuw G, Herrmann N. Cholinesterase inhibitor discontinuation in patients with Alzheimer's disease: a meta-analysis of randomized controlled trials. The Journal of Clinical Psychiatry. 2015 Nov 25;76(11):2613.
3. Reeve E, Farrell B, Thompson W, Herrmann N, Sketris I, Magin P, Chenoweth L, Gorman M, Quirke L, Bethune G, Forbes F. Evidence-based clinical practice guideline for deprescribing cholinesterase inhibitors and memantine in people with dementia. Recommendations. The University of Sydney, Sydney, Australia. 2018
4. Parsons C, Lim WY, Loy C, McGuinness B, Passmore P, Ward SA, Hughes C. Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia. Cochrane Database of Systematic Reviews. 2021(2).
5. Herrmann N, O'Regan J, Ruthirakuhan M, Kiss A, Eryavec G, Williams E, Lanctot KL. A randomized placebo-controlled discontinuation study of cholinesterase inhibitors in institutionalized patients with moderate to severe Alzheimer disease. Journal of the American Medical Directors Association. 2016 Feb 1;17(2):142-7.
6. Niznik JD, Zhao X, He M, Aspinall SL, Hanlon JT, Nace D, Thorpe JM, Thorpe CT. Impact of deprescribing AChEIs on aggressive behaviors and antipsychotic prescribing. Alzheimer's & Dementia. 2020 Apr;16(4):630-40.