#417 Deprescribing Cholinesterase Inhibitors: Good or bad idea?
CLINICAL QUESTION
What are the effects of deprescribing cholinesterase inhibitors?
BOTTOM LINE
Benefits of cholinesterase inhibitors are unclear, especially when dementia progresses. In patients with moderate-severe Alzheimer’s dementia, deprescribing cholinesterase inhibitors, on average, worsens cognition by 1-2 points on the Mini-Mental-State-Examination (MMSE). Randomized Controlled Trials (RCT) have not assessed the proportion of patients with clinically meaningful worsening of cognition or neuropsychiatric symptoms.
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EVIDENCE
- Results statistically significant unless indicated.
- MMSE (1-30, high=better),1,2 clinically meaningful difference: 1.4-2.
- Neuropsychiatric inventory (NPI) (1-144, low=better),2clinically meaningful difference: 8.
- Severe dementia, participants already on anticholinesterase inhibitors (mostly >2 years):
- Participants with MMSE~9:
- 146 participants, randomized to placebo (with taper) or continuation donepezil for 52 weeks.2
- MMSE: Baseline ~9, changed to ~3.5 (placebo) versus ~5.5 (donepezil).
- NPI: Not statistically different.
- 40 participants, randomized to placebo (with taper) or continuation donepezil/galantamine for 8 weeks.3
- MMSE: Not statistically different.
- 146 participants, randomized to placebo (with taper) or continuation donepezil for 52 weeks.2
- MMSE~1:
- 65 participants, randomized to placebo or continuation donepezil/memantine (no taper) for 12 weeks.4
- Cognitive examination (1-25, higher=better): Donepezil/memantine 0.9 better.
- NPI: Not statistically different.
- 65 participants, randomized to placebo or continuation donepezil/memantine (no taper) for 12 weeks.4
- Participants with MMSE~9:
- Moderate dementia:
- MMSE~19-21:
- 202 participants tolerating donepezil but without benefits after 12 weeks, randomized to placebo (no taper) or continuation for another 12 weeks.5
- MMSE: Baseline ~19, changed to ~19.5 (placebo) versus ~20.5 (donepezil).
- NPI: Donepezil 3.2 better.
- 96 participants tolerating donepezil after 12 weeks, randomized to placebo (no taper) or continuing donepezil for 12 weeks.1
- MMSE: Baseline 21, changed to ~19 (placebo) versus ~21 (donepezil).
- NPI: Donepezil 6.2 better.
- 202 participants tolerating donepezil but without benefits after 12 weeks, randomized to placebo (no taper) or continuation for another 12 weeks.5
- MMSE~19-21:
- Overall adverse events: No difference.6
- Systematic review including two RCTs with galantamine: Similar. 6
- Limitations: Poor adherence; industry funding; 1,5 unclear if scale changes reflect return to baseline (as if medication never started) versus clinical worsening; limited functional assessment data.6
CONTEXT
- Patients with adverse effects should stop cholinesterase-inhibitors.6,7
- Long-term use is controversial due to short duration/limitations of RCTs. 6,7
- Guideline: Consider stopping in those without benefits through shared decision-making with individuals/caregivers.7
- Possible severe withdrawal reactions in case reports (agitation, hallucinations).
- Tapering recommended, example: Halve dose every four weeks.
- Monitor, consider re-initiation if worsening of condition.
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