Deprescribing Cholinesterase Inhibitors and Memantine in People With Dementia

A Sensitive Issue

Linda Brookes, MSc

Disclosures

March 06, 2018

Finally, Guidance on Cholinesterase Inhibitor and Memantine Deprescribing

The latest clinical practice guideline from the Deprescribing Guidelines for the Elderly Project, based at the Bruyère Research Institute, Ottawa, Canada, focuses on the discontinuation of cholinesterase inhibitors and memantine, drugs approved for use in Alzheimer disease.[1] This guideline, which was developed jointly with the University of Sydney and the National Health and Medical Research Council (NHMRC) Cognitive Decline Partnership Centre, Sydney, Australia, is the first anywhere to be dedicated solely to the discontinuation of these drugs and the first to involve consumers in its development. Like the previous guidelines in the Bruyère series, it is accompanied by a summary deprescribing algorithm.[2] Its recommendations follow international criteria and are applicable to clinical practice worldwide.

Medscape spoke with the guideline's lead author, Emily Reeve, PhD, NHMRC-Australian Research Council Dementia Research Fellow, University of Sydney, and Dalhousie University, Halifax, Nova Scotia, Canada, to learn about the unique challenges involved in the preparation of this guideline and its recommendations.

As many as one third of cholinesterase inhibitor prescriptions are inappropriate.

Although there is no known cure for Alzheimer disease, current treatment guidelines generally recommend a cholinesterase inhibitor (ChEI)—for example, donepezil, rivastigmine, or galantamine—as the first-line treatment in mild-to-moderate disease. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, may be used in later stages.[3] Donepezil is also approved for use in severe Alzheimer disease in the United States and Canada, and can be given in addition to memantine or, in the United States, as a fixed-dose combination with memantine. These drugs have all been shown to delay or slow worsening of symptoms to some degree, but their effectiveness varies from person to person.

As many as one third of ChEI prescriptions are inappropriate, according to studies discussed in the guideline.[1] in addition, up to 80% of patients taking ChEIs have been reported to experience adverse drug-related effects (ADRs).[4] In clinical trials, most ADRs (principally gastrointestinal) were reported to be transient, occurring at the start of treatment, but more serious ADRs have been reported in practice. "Although severe side effects are rare, cardiovascular effects, like slowing heart rate and life-threatening dermatologic conditions, have been reported with these drugs," Dr Reeve noted.

One third of ChEI ADRs may be due to drug-drug interactions. People with dementia are likely to be taking five to 10 regular medications, and 9% to 45% of ChEI/memantine users are also prescribed a medication that could reduce its efficacy or result in a drug-drug interaction.

A particular concern is the prescription of anticholinergics to treat urinary incontinence, a potential side effect of ChEIs, Dr Reeve noted. "Since the two drug classes have opposite mechanisms of action, combinations like this need to be carefully considered in the individual," she commented.

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