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

Abstract

BACKGROUND

Acetylcholinesterase inhibitors such as donepezil are frequently discontinued in older adults with dementia when adverse events emerge, when perceived benefit declines, or during transitions to institutional care. Abrupt discontinuation may be followed by cognitive or behavioural deterioration, although the clinical phenotype and causal mechanisms remain incompletely defined.

CASE SUMMARY

An 89-year-old woman with a 10-year history of Alzheimer disease had received donepezil 10 mg/day for more than 5 years. Two weeks before nursing-home admission, reduced spontaneous speech and functional decline were already noted, with Hasegawa Dementia Scale-Revised declining from 16/30 to 8/30. Donepezil was abruptly stopped on day 0 at admission. Forty-eight hours later, she developed acute agitation, verbal aggression, insomnia and new gait instability, with a positive confusion assessment method assessment on day 2-3. Infection, major metabolic disturbance and acute structural cerebrovascular disease were not identified. Donepezil 5 mg/day was restarted on day 7, while as-needed quetiapine 12.5 mg was also used during the early post-rechallenge period. Agitation and verbal aggression decreased within 5 days, quetiapine was discontinued, sleep normalized by day 12, and by day 21 she was eating independently and adapting to the facility. The clinical interpretation remained provisional because several alternative or contributing explanations could not be fully excluded.

CONCLUSION

The temporal sequence and improvement after donepezil rechallenge are compatible with suspected donepezil withdrawal, but the diagnosis remains provisional and causality is uncertain. Natural dementia progression, nursing-home relocation, occult pain, unrecorded over-the-counter drugs or supplements, non-convulsive seizures, and concomitant quetiapine are alternative or contributing explanations. The 48-hour onset does not imply complete drug elimination because donepezil has a long elimination half-life; rather, it is compatible with an early clinical response to a falling drug exposure, although this mechanism cannot be demonstrated in the present case. Abrupt discontinuation should therefore be approached cautiously and monitored clinically.

Keywords: Donepezil; Withdrawal syndrome; Delirium; Behavioral and psychological symptoms of dementia; Nursing-home admission; Older adults; Case report

Core Tip: Abrupt discontinuation of long-term donepezil was followed 48 hours later by agitation, insomnia and gait instability in an 89-year-old woman who had taken 10 mg/day for more than five years. Symptoms improved after rechallenge with 5 mg/day, but interpretation is limited by pre-existing cognitive decline, nursing-home relocation, concomitant quetiapine and other unmeasured factors. The case illustrates why suspected withdrawal may be considered in the differential diagnosis without assuming that all post-discontinuation deterioration is drug-related.