Objective: Traditionally, the neuropsychiatric symptoms of Alzheimer’s disease (AD) have been managed with neuroleptics or benzodiazepines, which have serious side effects. Preliminary observations suggest the possible value of cholinesterase inhibitors in the amelioration of psychotic symptoms in patients with dementia of the Alzheimer’s type, dementia with Lewy bodies and patients suffering from Parkinson’s disease.
Design: Open-label
Materials and Methods: Twelve inpatients suffering from AD with psychotic symptoms and lack of improvement of their delusions/hallucinations during perphenazine treatment (8 mg/day) for three weeks received open-label randomly 5 mg/day donepezil in addition to an ongoing 8 mg/day perphenazine treatment or 16 mg/day perphenazine. Assessments conducted at baseline and after weeks two and four, included the Mini-Mental State Examination (MMSE), the Global Deterioration Scale (GDS), Positive and Negative Symptoms Scale (PANSS), the Clinical Global Impressions scale (CGI). Frequency of extrapyramidal symptoms was measured according to the Abnormal Involuntary Movement Scale (AIMS).
Results: The donepezil-perphenazine group exhibited substantially greater and significant improvements in clinical state. At the end of the trial (4 weeks) PANSS scores revealed significant differences between the both groups (P=.006). The CGI and the MMSE scores also showed significant differences between the donepezil-perphenazine group and perphenazine group, accordingly (P=.028) and (P=.027). No significant differences were found for the GDS scores. AIMS scores showed a significant deterioration in extrapyramidal symptoms in the perphenazine group in comparison to donepezil-perphenazine group (P =.016).
Conclusion: Donepezil augmentation of neuroleptics may be appropriate for those patients for whom neuroleptics monotherapy either does not lead to symptom remission, or is associated with intolerable adverse effects. It was an open-label study and there is a need for further and greater studies with double-blind control and a long-term study design in order to define the efficacy of donepezil for patients with AD and psychotic symptoms.
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