Donepezil Treatment of Psychotic Symptoms in Dementia Patients

Criteria for inclusion into the study will be: 1) DSM-IV diagnosis of Dementia of the Alzheimer type with psychotic symptoms such as hallucinations and delusions, aggression/agitation, irritability, and disinhibition that called for the administration of antipsychotic drugs; 2) duration of psychotic symptoms at least 2 weeks before beginning of treatment; 3) lack of improvement of psychotic symptoms (less than 25% on Positive and Negative Symptoms Scale (PANSS) during perphenazine treatment (8 mg/day) for at least three weeks; 4) drug regimen for physical disease of all patients was unchanged for at least three months before the study. Exclusion criteria include: 1) a vascular dementia; 2) concurrent Axis I DSM-IV diagnoses (delirium, schizophrenia, delusional disorders, and affective disorders) 3) significant medical illness (cardiovascular, liver, renal, endocrinal, vitamin B12 or folic acid deficiency, and neurological illnesses); 4) drug or/and alcohol addiction. The study design will be a double blind group study, lasting for 9 weeks. Complete physical and laboratory examinations will be performed on all inpatients. Subjects will be randomized in a 1:1 fashion to receive treatment with 4 mg of perphenazine or 5 mg of donepezil or placebo in addition to the perphenazine treatment (8 mg/day) that they have received for the past 3 weeks (baseline). According to mental state (improvement less than 20% on PANSS scores), perphenazine dose will be elevated by 4 mg/day to maximum 16 mg/day in the first group, and donepezil dose will be increased by 5 mg/day to maximum 10 mg/day in the second group) and placebo will be elevated up to 2 capsules/day in the third group. All preparations will be administered in identical capsules made by a professional pharmacist, and supplied in individual number-coded packages. Assessments for psychotic symptoms will be done using PANSS and CGI at baseline and repeated weekly. Assessments for extrapyramidal side effects will be done using AIMS at baseline and repeated every week. In addition, both at the beginning and at the end of the study, all patients will be assessed with MMSE and GDS. Complete blood profiles, and urine analysis will be performed at screening and at week 9. References 1. Evans DA. Estimated prevalence of Alzheimer's disease in the United States. Milbank Q 1990;68:267-89. 2. Schneider LS. Pharmacologic management of psychosis in dementia. J Clin Psychiatry 1999;60(Suppl 8):54-60. 3. Tariot PN. Treatment of agitation in dementia. J Clin Psychiatry 1999;60(Suppl 8):11-20. 4. Levy ML, Cummings JL, Kahn-Rose R. Neuropsychiatric symptoms and cholinergic therapy for Alzheimer's disease. Gerontology 1999;45(Suppl 1):15-22. 5. Casey DE. Side effect profiles of new antipsychotic agents. J Clin Psychiatry 1996;57(Suppl 11):40-5. 6. Zayas EM, Grossberg GT. The treatment of psychosis in late life. J Clin Psychiatry 1998;59(Suppl 1):5-10. 7. 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