Stopping acetylcholinesterase inhibitor or memantine therapy

If the criteria for stopping an acetylcholinesterase inhibitor or memantine are not met, but deprescribing is considered, seek specialist advice (eg geriatrician, psychiatrist, neurologist).
If a criterion for stopping an acetylcholinesterase inhibitor or memantine is met, engage in shared decision making with the patient or their substitute decision-maker. Discuss:
  • the process of stopping the drug (described below)—highlight this process is a trial and therapy can be resumed if required
  • the potential benefits and harms of continuing the drug versus stopping it
  • any fears and concerns of the patient or their substitute decision-maker about stopping the drug.

If stopping an acetylcholinesterase inhibitor or memantine, make a plan with the patient or their substitute decision-maker, the patient’s significant other(s) or carer(s), and other relevant healthcare professionals. The plan should set out an approach to monitoring, dosage adjustment and indicators for resuming the drug.

It is preferable to avoid abruptly stopping therapy—instead, slowly reduce the dosage and regularly assess the patient during the process to:

  • reduce the risk of severe withdrawal reactions (eg agitation, aggression, hallucinations, impaired consciousness)
  • reduce the impact of cognitive, functional and behavioural or psychological symptoms if they reoccur (these changes can be irreversible)
  • determine the minimum effective dosage if the drug cannot be stopped.

Halve the dosage every 4 weeks until the lowest dose possible is used for 4 weeks, then stop. If available formulations do not allow the dose to be halved, step down through available formulations. Adjust the speed of dosage reduction depending on the reason for stopping the drug (eg stop therapy immediately if the drug has caused a severe adverse effect) and patient response.

During dosage reduction, assess cognition, function, and behavioural and psychological symptoms at a minimum of every 4 weeks—more frequent monitoring may be required depending on the situation. Between assessments, the patient and/or their significant other(s) and/or carer(s) should watch for signs of deterioration and seek medical advice if symptoms worsen. If the patient deteriorates during dosage reduction or after the drug has been stopped, before attributing their symptoms to drug withdrawal, consider alternative causes (eg delirium).

If a severe withdrawal reaction (ie worsening agitation, aggression, hallucinations, reduced consciousness) occurs within a week of dosage reduction or stopping therapy, immediately resume therapy at the previous minimum effective dosage.

If cognition, function, or behavioural and psychological symptoms worsen after more than a week, but less than 6 weeks after dosage reduction or stopping therapy, it is likely symptoms that were previously treated by the drug are re-emerging. Consider resuming therapy at the previous minimum effective dose.

If cognition, function, or behavioural and psychological symptoms worsen after more than 6 weeks, but less than 3 months after dosage reduction or stopping therapy, this may due to be symptom re-emergence or natural dementia progression. Beyond 3 months, symptom worsening is usually due to dementia progression.