METHODS: Case report.
RESULTS: The authors report a case of a manic episode with psychotic features associated with the up-titration of donepezil in a patient with Alzheimer\'s disease and a distant history of major depression but without a preexisting bipolar disorder.
CONCLUSIONS: Pathophysiology of donepezil-induced mania appears to contradict the traditional cholinergic-adrenergic hypothesis. Donepezil-associated mania should be suspected after donepezil initiation/dose up-titration when correlated to new onset of mania. Donepezil should be used more cautiously in patients with current or previous mood episodes or in those who are otherwise at high risk for manic episodes (e.g., cerebrovascular disease). Although this requires further investigation in different patient populations, there may be subtypes of older patients with neurocognitive disorders who are particularly vulnerable to activation effects of cholinesterase inhibitors.