Deprescribing Cholinesterase Inhibitors and Memantine in People With Dementia

A Sensitive Issue

Linda Brookes, MSc


March 06, 2018

Advantages and Disadvantages of Deprescribing

Deprescribing ChEIs/memantine can reduce the risk for ADRs and drug-drug and drug-disease interactions. It can also reduce the pill burden for patients and improve adherence to other medications, as well as reduce the medication management burden for caregivers and reduce medication costs. However, abruptly stopping these drugs may also result in a worsening in cognition and/or behavior as well as adverse drug withdrawal reactions in some individuals.

One barrier to deprescribing ChEIs/memantine is that clinicians are not sure when or how to do it, and consequently there is some fear about it.

Families and caregivers of people with dementia can feel guilty that they are "giving up" on the patient if the possibility of deprescribing is broached. One of the goals of the guideline is to encourages discussion with the patient and family members or caregivers across all points of care and to increase awareness that optimal medication management involves deprescribing as well as prescribing. "Even when these medications are being started, the discussion should include how, at some point, we are going to try stopping them," Dr Reeve said.

One barrier to deprescribing ChEIs/memantine is that clinicians are not sure when or how to do it, and consequently there is some fear about it, Dr Reeve noted. "A few of the current treatment guidelines mention stopping, but in a very vague way; and there is much less clear information on how to stop the drugs than how to start them," she explained. The new guideline aims to help clinicians identify the most suitable patients for deprescribing—those who are likely to benefit or not experience harm from withdrawal of ChEIs/memantine—and how to withdraw the drugs, what to monitor, and what to do if the symptoms return.

The State of the Evidence

The recommendations are consensus- rather than evidence-based, as a result of limited or low-quality evidence. Like earlier reviewers,[5,6] the guideline authors point to the lack of appropriate study data on ChEIs/memantine withdrawal. Dr Reeve and her colleagues identified only seven randomized controlled trials of withdrawal versus continuation of ChEIs (including six in Alzheimer disease) and none on the discontinuation of memantine. "We don't have a lot of good information outside of the initial randomized clinical treatment trials, which we know aren't really a good representation of the wider population who end up taking these drugs," Dr Reeve cautioned. From their review of the evidence available, including observational data, they concluded that despite the potential for worsened outcomes (especially in cognition) after discontinuation of these drugs in some patients, in others, the risk-benefit ratio favors discontinuation rather than continuation.


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