Violent Behavior Associated With Donepezil
To the editor: We report a case of violent behavior following the commencement of donepezil, the first recently introduced reversible cholinesterase inhibitor in this country. The indication for donepezil is symptomatic treatment of mild or moderate dementia in Alzheimer"s disease. Donepezil is thought to work by increasing the availability of intrasynaptic acetylcholine in the brains of patients with Alzheimer"s disease (1).
Mr. A, a 76-year-old man with a 2-year history of cognitive impairment, was clinically diagnosed as suffering from Alzheimer"s disease according to ICD-10 (2). His Mini-Mental State score (3) was 17 of 30. There was no history of violence or behavioral disturbances, and no psychotic phenomena were elicited. Apart from an unstable bladder requiring prescription of oxybutinin, 3 mg t.i.d. for the past 5 years, Mr. A’s medical history was unremarkable. A physical examination and routine laboratory investigations showed no abnormalities, apart from an intermittent parkinsonian tremor of his left hand. This raised the possibility of a diagnosis of dementia with Lewy bodies (4), although no other features were present. Mr. A was started on a regimen of donepezil, 5.0 mg daily.
Five days later, Mr. A became very paranoid, believing that his wife had been stealing his money. He beat his wife and held her hostage in their house with a knife until their daughter intervened. Mr. A agreed to hospital admission, avoiding compulsory detention.
Physical and laboratory investigations were repeated, including a computerized tomography scan of the brain showing no abnormalities apart from generalized atrophy. Mr. A was started on a regimen of haloperidol, 0.5 mg b.i.d., while his donepezil and oxybutinin were discontinued. His paranoid ideation resolved within a few days and did not reoccur, despite withdrawal of haloperidol.
Although a causal relationship between this violent incident and donepezil cannot be proven, a temporal relationship between the commencement of donepezil and the occurrence of behavioral disturbance in Mr. A, a patient with no previous history of violence, warrants caution with the prescription of this drug. The manufacturer reports that 5% of patients taking donepezil have developed agitation, although only 1% with physical aggression (personal communication). We suggest the need for close specialist monitoring of this recently licensed drug.
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