Deprescribing Cholinesterase Inhibitors and Memantine in People With Dementia

A Sensitive Issue

Linda Brookes, MSc


March 06, 2018

When and How to Deprescribe

A major challenge for clinicians is determining whether patients using these medications are still benefiting from them. "We chose not to include a specific cutoff in terms of tools like MMSE (Mini-Mental Status Examination) or ADAS-Cog (Alzheimer's Disease Assessment Scale-Cognitive) for a recommendation to deprescribe because we didn't think the evidence supported doing that. There are limitations of those kinds of tools and there is huge variability in how people respond," Dr Reeve explained. Deprescribing still requires assessment and judgment by the patient's clinician, but it must eventually be a shared decision based on discussion with the patient (if possible) and their family or caregivers, she emphasized. "We talk with them about their treatment goals—that is, what they value most. Is it cognition, quality of life, or staying independent? And we explain that as someone ages, the benefits and harms of the medication can change," she said. "We look at the patients' symptoms over the past 6 months, their present condition, and what real impact this is going to have for the remainder of their life."

The guideline stresses that deprescribing should begin as a trial discontinuation, with close periodic monitoring.

The new guideline applies to anyone18 years of age or older who has been taking ChEI/memantine for Alzheimer disease, dementia associated with Parkinson disease, Lewy body dementia, vascular dementia, or for other indications. Consideration of a trial of deprescribing is recommended in patients who have been taking the medication for more than 12 months and have shown significantly worsening cognition or function over the previous 6 months (compared with previous progress) or have not demonstrated benefit from the drug (improvement, stabilization, or decreased rate of decline during treatment), as well as in those with severe/end-stage dementia.

Deprescribing is also suggested in the following circumstances:

The guideline stresses that deprescribing should begin as a trial discontinuation, with close periodic monitoring (eg, every 4 weeks). The dose of ChEI/memantine should be tapered by halving the dose or by stepping down through available dose formulations every 4 weeks to the lowest available dose, followed by discontinuation. "If there seems to be a clear worsening of symptoms at any time up to 3 months after dose reduction or cessation, after exclusion of other causes, then the medication can be restarted," Dr Reeve said. "Based on the limited evidence available, there doesn't appear to be any long-term harm associated with a temporary dose reduction or stopping," she noted. After 3 months, any worsening is likely to be due to disease progression rather than re-emergence of symptoms.

  • The patient or family members/caregivers wish to discontinue the medication;

  • The patient refuses or is unable to take the medication;

  • Nonadherence cannot be resolved;

  • Drug-drug or drug-disease interactions make treatment risky;

  • Severe agitation/psychomotor restlessness; or

  • Non-dementia terminal illness.

Future Guideline Updates

The guideline authors point to "significant gaps in the literature," and they predict that future studies may lead to changes in the recommendations. "Even though we found quite a few studies that we were able to base our recommendations on, one of the major limitations was the wide variability in the different populations studied," Dr Reeve said. "So we would benefit from more evidence for identifying the people in whom we can stop the drugs and then follow up to be able to strengthen those recommendations and more evidence about whether tapering is the best way to go about it." The authors aim to update the guideline online as new evidence emerges. One study that is expected to come under consideration within the next 2 years is the Cholinesterase Inhibitors Discontinuation (CID) trial,[7] sponsored by the US government's Veterans Affairs Office of Research and Development. This study is comparing dose reduction followed by discontinuation versus sham discontinuation in elderly adults taking a daily dose of donepezil ≥ 10 mg or galantamine ≥ 8 mg.[7] "I think the research that is being done now and being started in deprescribing is becoming a lot more strategic, and it really is targeted towards those areas of most uncertainty," Dr Reeve commented.


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