Cognitive enhancers (cholinesterase inhibitors and memantine) are used in patients with dementia (called major neurocognitive disorder in DSM-5-TR™) of several different types. But, once they are started, they are often continued indefinitely. Yet, their potential benefits and the risk of harms can change over time (Reeve et al., 2019). Importantly, deprescribing cholinesterase inhibitors may reduce the risk of serious falls or fractures (Niznik et al., 2020).
Cholinesterase inhibitors were one of the types of medications for which clinicians said that a deprescribing guideline would be useful (Farrell et al., 2015). But, in the past, textbooks and practice guidelines provided little specific guidance regarding deprescribing cholinesterase inhibitors (Renn et al., 2018).
More recent practice guidelines have provided specific, helpful recommendations about when and how to desprescribe cholinesterase inhibitors, which will be summarized below. Recommendations for deprescribing memantine will be discussed in a separate article on this website.
In what situations is stopping cholinesterase inhibitors recommended?
The 5th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD5; Ismail et al., 2020) and an Australian practice guideline on deprescribing cholinesterase inhibitors and memantine in dementia (Reeve et al., 2019) made very similar recommendations about deprescribing cholinesterase inhibitors. Our recommendations below are based mainly on these two practice guidelines. But the text of the recommendations has been edited and emphasis in red has been added by us.
Scenario no. 1: The patient is taking a cholinesterase inhibitor for more than 12 months for Alzheimer’s disease, Parkinson’s disease dementia, Lewy body dementia, or vascular dementia.
In these patients, we should consider stopping the cholinesterase inhibitor in the following situations (Ismail et al., 2020; Reeve et al., 2019):
1. The cholinesterase inhibitor does not appear to have been significantly helpful at any time since it was started.
That is, treatment with the cholinesterase inhibitor was not associated with either improvement, stabilization, or decreased rate of decline.
Barry Rovner, MD, adds: Patients with dementia are expected to decline even while on a cholinesterase inhibitor. Nevertheless, they still might be deriving some benefit. The only way to know is to see what happens after the cholinesterase inhibitor is stopped. I’ve seen people appear worse once the medication is stopped, even though they had been gradually declining before then. So, if the decision is made to taper and discontinue a cholinesterase inhibitor, we should monitor for possible worsening soon afterward because that may suggest that the cholinesterase inhibitor had, in fact, been helpful to some extent.
2. The dementia has worsened to a significant extent—as evidenced by changes in cognition, functioning, or global assessment over the past 6 months—even though no other medical conditions or environmental factors have been present that could have contributed to the observed worsening.
3. The patient has severe or end-stage dementia.
Here, severe or end-stage dementia means any of the following: being dependent in terms of most of the basic activities of daily living, being unable to respond to the environment, or having a limited life expectancy.
4. The cholinesterase inhibitor is causing intolerable side effects.
Examples of intolerable side effects that can occur with cholinesterase inhibitors include severe nausea, vomiting, weight loss, anorexia, falls, and so on.
5. Poor adherence to the medication, which either prevents continuation of the cholinesterase inhibitor in a safe manner or does not allow assessment of its effectiveness.
Scenario no. 2
If the cholinesterase inhibitor is being given for an indication other than Alzheimer’s disease, Parkinson’s disease dementia, Lewy body dementia, or vascular dementia, it should be discontinued (Ismail et al., 2020; Reeve et al., 2019).
In what situations should we NOT stop the cholinesterase inhibitor?
Scenario no. 1
If the patient had a significant reduction in neuropsychiatric symptoms with the cholinesterase inhibitor, it should be continued even if cognitive and functional decline has occurred.
Scenario no. 2
Cholinesterase inhibitors should not be discontinued in patients with significant current psychotic symptoms, agitation, or aggression until these symptoms have stabilized (Ismail et al., 2020). An exception to this recommendation is that the symptoms worsened when the cholinesterase inhibitor was started or its dose was increased (Ismail et al., 2020).
Scenario no. 3
Vimal Aga, MD adds: The cholinesterase inhibitor should be continued as long as the patient is still receiving a specific medication that has been associated with a significant reduction in the target neuropsychiatric symptoms.
The neuropsychiatric symptoms in patients with dementia that may have been targeted and the specific medications that may have been used include:
– Aggression/agitation treated with, for example, citalopram or brexpiprazole
– Apathy treated with, for example, methylphenidate.
Here are his reasons for making this recommendation:
1. In recent clinical trials for neuropsychiatric symptoms in patients with dementia, the majority of patients were also on a cholinesterase inhibitor or memantine (Lee et al., 2023; Mintzer et al., 2021; Grossberg et al., 2020; Porsteinsson et al., 2014; Rosenberg et al., 2013).
2. There is evidence that cholinesterase inhibitors reduce the need for antipsychotic medication in patients with Alzheimer’s Disease and Parkinson’s Disease dementias. The effect sizes were small, but even a small reduction in the need for these medications may be meaningful clinically, given the risks associated with antipsychotic use in patients with dementia.
Simple and Practical Medical Education thanks (alphabetically) Vimal Aga, MD, DFAPA, and Barry Rovner, MD, for their helpful input, expert review, and final approval of this article. Drs. Aga and Rovner are both geriatric psychiatrists with extensive clinical experience.
Dr. Aga is an Adjunct Assistant Professor in the Department of Neurology at Oregon Health and Science University in Portland, Oregon, and works at Layton Center for Aging and Alzheimer’s Disease and at the Geriatric Psychiatry Program of the Oregon State Hospital in Salem, Oregon. Dr. Rovner is a Professor of Psychiatry and Neurology at Thomas Jefferson University in Philadelphia, Pennsylvania.
Related Pages
Treatments—Cognitive Enhancers—Cholinesterase Inhibitors
Alzheimer’s disease: Medications
How to choose a cholinesterase inhibitor
Switch cholinesterase inhibitors?
Medications for dementia: Alternative preparations
Donepezil (Aricept®, Aricept ODT®): Basic Information
Galantamine (Razadyne, Razadyne ER): Basic Information
Rivastigmine (Exelon®, Exelon® Patch): Basic Information
Treatments—Cognitive Enhancers—Memantine
Memantine (Namenda®, Namenda XR®): Basic Information
Mental Disorders—Major Neurocognitive Disorder (Dementia)
Neurocognitive disorders in DSM-5
Tips for interviewing patients with dementia
First, which cognitive domains are impaired and to what extent?
Montreal Cognitive Assessment (MOCA)
What is Lewy body dementia?
An introduction to Neurocognitive disorder with Lewy bodies
Resources—Practice Guidelines
Practice guidelines for Alzheimer’s disease and other dementias (DSM-5-TR™: Major neurocognitive disorder)
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References
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