At what point is it appropriate to discontinue Alzheimer's disease medications, such as Cholinesterase inhibitors (e.g., Donepezil), and do they require a taper, with consideration of potential worsening of dementia or Alzheimer's disease symptoms after discontinuation?

From the Guidelines

Discontinuation of Alzheimer's medications should be considered when there is a clinically meaningful worsening of dementia, no clinically meaningful benefit, severe or end-stage dementia, intolerable side effects, or poor medication adherence, as recommended by the 5th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 1. When deciding to discontinue Alzheimer's medications, it is essential to consider the patient's preferences, prior expressed wishes, and collaboration with family or substitute decision makers. The decision to discontinue should be based on individualized assessment, taking into account the patient's response to treatment, disease progression, and quality of life.

Considerations for Discontinuation

• Clinically meaningful worsening of dementia, as reflected in changes in cognition, functioning, or global assessment over the past 6 months, in the absence of other medical conditions or environmental factors that may have contributed to the decline 1.
• No clinically meaningful benefit observed at any time during treatment, such as improvement, stabilization, or decreased rate of decline 1.
• Severe or end-stage dementia, characterized by dependence in most basic activities of daily living, inability to respond to environment, or limited life expectancy 1.
• Development of intolerable side effects, such as severe nausea, vomiting, weight loss, anorexia, falls, confusion, dizziness, or other significant adverse effects 1.
• Poor medication adherence, which precludes safe ongoing use of the medication or inability to assess the effectiveness of the medication 1.

Tapering and Discontinuation

• Deprescribing of cholinesterase inhibitors (ChEIs) or memantine should occur gradually, with treatment reinitiated if the individual shows clinically meaningful worsening of cognition, functioning, neuropsychiatric symptoms, or global assessment that appears to be related to cessation of therapy 1.
• Dose reduction during deprescribing should follow general guidelines, with a reduction of dose by 50% every 4 weeks until the initial starting dose is obtained, and then the cognitive enhancer could be discontinued after 4 weeks of treatment on the recommended starting dose 1.

Special Considerations

• Cholinesterase inhibitors should not be discontinued in individuals who currently have clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms have stabilized, unless these symptoms appear to have been worsened by the initiation of a ChEI or an increase in ChEI dose 1.
• Individuals who have had a clinically meaningful reduction in neuropsychiatric symptoms with cognitive enhancers should continue to be treated with the cognitive enhancer, even if there is evidence of cognitive and functional decline 1.
• Cholinesterase inhibitors and memantine should be deprescribed for individuals with mild cognitive impairment 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Discontinuing Alzheimer's Medication

• The decision to stop therapy should involve the resident, family, caregivers, and providers 2
• Therapy is generally discontinued if these agents prove to be ineffective or are not tolerated 2
• All medications should be continuously evaluated for clinical efficacy and, when appropriate, discontinued if the primary benefit is no longer being achieved 3

Tapering Alzheimer's Medication

• There is no clear evidence on the need for tapering Alzheimer's medication, but antipsychotic medications, which are sometimes used off-label to treat behavioral symptoms of Alzheimer's disease, may require a taper when discontinuing 4
• Gradual withdrawal schedules were used in some studies of antipsychotic withdrawal in people with dementia 4

Dementia or Alzheimer's Worsening After Stopping Medication

• The effectiveness of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer's disease has been shown to stabilize or slow decline in cognition, function, behavior, and global change 5
• Withdrawal of antipsychotic agents in older people with dementia did not lead to significant deterioration in behavior in most studies, but people with more severe baseline neuropsychiatric symptoms may be at risk of behavioral deterioration after withdrawal 4
• Discontinuation of antipsychotic medication may lead to an increased risk of relapse in people whose agitation or psychosis had previously responded well to antipsychotic treatment 4