American Society of Consultant Pharmacists

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Released May 17, 2021

Don’t use anticholinergic medications concomitantly with cholinesterase inhibitors in patients with dementia.

Anticholinergics (e.g. overactive bladder medications and first-generation antihistamines) competitively inhibit binding of the neurotransmitter acetylcholine, thus reducing the effects of acetylcholine. Cholinesterase inhibitors, used in the treatment of dementia, act by blocking the enzyme acetylcholinesterase thereby inhibiting acetylcholine degradation. Therefore, pharmacologic actions of anticholinergics and cholinesterase inhibitors oppose each other. Concomitant use of anticholinergics with cholinesterase inhibitors reduces the effectiveness of antidementia drugs, the benefits of which are modest at best; concomitant use increases the risk of adverse effects of anticholinergics and may also increase the rate of functional and cognitive decline. Medications with anticholinergic properties are commonly prescribed to treat comorbidities associated with dementia and sometimes the adverse effects of cholinesterase inhibitors. Patients with dementia are sensitive to cognitive impairment induced by medications with anticholinergic properties. In general, it has been recognized that anticholinergics are known to adversely affect cognition in older patients and even more so with concomitant dementia diagnosis.


These items are provided solely for informational purposes and are not intended as a substitute for consultation with a medical professional. Patients with any specific questions about the items on this list or their individual situation should consult their physician.

How The List Was Created

(1–5)

A deprescribing task force led by chair (Manju T. Beier, Pharm D, BCGP, FASCP) was created by ASCP in November 2018. Members comprised of pharmacists practicing in academia, community and long-term care settings. The chair also invited pharmacists from international countries (Canada and Australia) where deprescribing initiatives have a strong focus and literature base. The collective experience and knowledge represent a focus on medication management, medication selection and reconciliation, and monitoring for drug-drug interactions (DDIs). The emphasis is on older adults no matter where they reside in step with ASCP’s mission.

Definition wise, deprescribing is a stepwise reduction of unnecessary or potentially inappropriate medications in concert with patient and family goals and wishes. We recognize that even with the best of intentions, many older adults are left on unnecessary and potentially dangerous or duplicative medications that might precipitate adverse events and other negative outcomes.

The task force prioritized formulation of the Choosing Wisely (CW) List, since the goals of CW intersect and overlap with deprescribing initiatives. The list was created to address general medication regimen review statements, and more importantly to address the paucity of statements that address DDIs with several incriminating medication therapeutic classes prescribed for older adults. After a review of published CW statements on www.choosingwisely.org and also a review of CW statements published by international countries, it was decided by consensus to have a strong emphasis on DDIs.

After several virtual meetings, the CW workgroup was divided into subgroups to formulate DDIs that have a strong evidence base in the literature and those that focus on CNS therapeutic classes, anticholinergic burden, heightened bleeding risk, and other pivotal pharmacokinetic and pharmacodynamic DDIs. For each statement the group formulated a rationale that was evidence-based accompanied with several recent, pertinent references. The compiled list (after several virtual meetings and email discussion) was further reduced to top ten statements with the strongest evidence base and practice trends on medication management in older adults.

The top five list was selected by consensus for initial submission.

Attached is a recently published guest editorial in ASCP’s journal that highlights the emphasis on DDIs.
Beier MT. Vigilance of Drug-Drug Interactions to Mitigate ADRs: Front and Center for Pharmacists (Guest Editorial). Sr Care Pharm 2020; 35:336-7.

(6–10)

A deprescribing task force led by chair (Manju T. Beier, Pharm D, BCGP, FASCP) was created by ASCP in November 2018. Members comprised of pharmacists practicing in academia, community and long-term care settings. The chair also invited pharmacists from international countries (Canada and Australia) where deprescribing initiatives have a strong focus and literature base. The collective experience and knowledge represent a focus on medication management, medication selection and reconciliation, and monitoring for drug-drug interactions (DDIs). The emphasis for all our statements is on older adults no matter where they reside in step with ASCP’s mission. Our first 5 CW statements were published in May 2021.

As previously addressed, the rationale for the new 2022 list (statements 6–10) includes one medication review statement in older adults with limited life expectancy, and three statements emphasizing the adverse combination of CNS medications that have a strong evidence base in the literature including tramadol’s potential for greater harm than benefit for pain relief, especially in older adults. We had previously highlighted pharmacodynamic DDIs for heightened bleeding risk, and this time our statement addresses the complexity of pharmacokinetic DDIs with Direct Oral Anticoagulants (DOACs).

Sources

Valladales-Restrepo LF, Duran-Lengua M, Machado-Alba JE. Potentially inappropriate prescriptions of anticholinergics drugs in Alzheimer’s disease patients. Geriatrics Gerontol Int 2019;19(9):913-7.

Ah Y-M, Suh Y, Jun K, Hwang S, Lee J-Y. Effect of anticholinergic burden on treatment modification, delirium and mortality in newly diagnosed dementia patients starting a cholinesterase inhibitor: A populationbased study. Basic Clin Pharmacol Toxicol 2019;124(6):741-8.

Gill S, Mamdani M, Naglie G, Streiner DL, Bronskill SE, Kopp A, et al. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Arch Intern Med 2005;165:808-13.

Boudreau DM, Yu O, Gray SL, Raebel MA, Johnson J, Larson EB. Concomitant use of cholinesterase inhibitors and anticholinergics: prevalence and outcomes. J Am Geriatr Soc 2011;59:2069-76.

Beier MT. Cholinesterase Inhibitors and Anticholinergic Drugs: Is the Pharmacologic Antagonism Myth or Reality? J Am Med Dir Assoc 2005;6(6):413-4.

Sink KM, Thomas J, Xu H, Craig B, Kritchevsky S, Sands LP. Dual use of bladder anticholinergics and cholinesterase inhibitors: Long-term functional and cognitive outcomes. J Am Geriatr Soc 2008;56:847–853.

Narayan SW, Pearson S, Litchfield M, Le Couteur DG, Buckley N, McLachlan AJ. Anticholinergic medicines use among older adults before and after initiating dementia medicines. Br J Clin Pharmacol
2019;85(9):1957-63.

Knight R, Khondoker M, Magill N, Stewart R, Landau S. A Systematic Review and Meta-Analysis of the Effectiveness of Acetylcholinesterase Inhibitors and Memantine in Treating the Cognitive Symptoms of

Dementia. Dement Geriatr Cogn Disord 2018;45(3-4):131-51.

By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am
Geriatr Soc 2019;67(4):674-694.