Suspected donepezil withdrawal syndrome in an older woman with Alzheimer disease of abrupt cessation: A case report

Table 1 Day-by-day clinical timeline from the pre-admission decline through 12-week follow-up

Day	Location	Donepezil/other medication	CAM/cognition	Key symptoms or events	Interpretation
-14 to -1	Home	Donepezil 10 mg/day; amlodipine 5 mg/day	HDS-R 16/30 previously; 8/30 at pre-admission review	Reduced spontaneous speech, withdrawal and increased prompting for ADLs	Pre-existing cognitive/functional decline
0	Nursing-home admission	Donepezil 10 mg/day stopped abruptly; amlodipine continued	No acute CAM assessment documented	Major environmental transition	Start of medication exposure change
1	Nursing home/home	No donepezil	Not documented	No detailed standardized assessment available	Early post-discontinuation period
2	Home	No donepezil	CAM-positive syndrome recognized over day 2-3	Acute agitation, verbal aggression, refusal to sit for meals, insomnia, new gait instability	48-hour temporal association
3	Emergency department	No donepezil	CAM positive; distractible, disorganized thinking	CT and routine laboratory work-up unremarkable; diagnosed clinically as delirium	Major infection/metabolic/structural causes not identified
4-6	Home	No donepezil	Not standardized	Persistent agitation and sleeplessness	Ongoing symptoms before rechallenge
7	Nursing-home review	Donepezil 5 mg/day restarted; quetiapine 125 mg PRN added	No standardized severity scale	Withdrawal suspected; quetiapine used almost daily during first week	Rechallenge, but confounded by rescue medication
8-11	Nursing home	Donepezil 5 mg/day; PRN quetiapine	Not standardized	Agitation and verbal aggression progressively decreased	Improvement during combined rechallenge/adaptation period
12	Nursing home	Donepezil 5 mg/day; quetiapine discontinued	Not standardized	Sleeping through the night	Early clinical improvement
21	Nursing home	Donepezil 5 mg/day	Not standardized	Eating independently and adapting to facility	Functional recovery
84	Nursing home	Donepezil 5 mg/day	No recurrence reported	12-week follow-up without recurrence	Longer-term follow-up

Days are grouped when separate daily documentation was unavailable, to avoid implying precision that was not supported by the retrospective record. CAM: Confusion assessment method; HDS-R: Hasegawa Dementia Scale-Revised; CT: Computed tomography; ADLs: Activities of Daily Living; PRN: Pro re nata.