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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.

REFERENCES

1. Rogers SL, Friedhoff LT: The efficacy and safety of donezepil in patients with Alzheimer's disease: results of a US multicentre, randomized, double blind, placebo-controlled trial. Dementia 1996; 7:293–303
2. World Health Organization: The ICD-10 Classification of Mental and Behavioural Disorders. Geneva, WHO, 1992
3. Folstein MF, Folstein SE, McHugh PR: Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189–198[Medline]
4. McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, Salmon DP, Lowe J, Mirra SS, Byrne EJ, Lennox G, Quinn NP, Edwardson JA, Ince PG, Bergeron C, Burns A, Miller BL, Lovestone S, Collerton D, Jansen EN, Ballard C, de Vos RA, Wilcock GK, Jellinger KA, Perry RH: Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996; 47:1113–1124[Abstract/Free Full Text]

Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by BOUMAN, W. P. Articles by PINNER, G. Search for Related Content Articles by BOUMAN, W. P. Articles by PINNER, G. Alzheimer's Disease Other Violence/Aggression

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