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From the Memory Assessment and Research Centre (Dr. Holmes, D. Wilkinson, C. Dean, and C. Clare), University of Southampton; Department of Mental Health for the Elderly (S. Vethanayagam), St Leonards on Sea; Melbury Lodge (Dr. Olivieri), Winchester; Pepperville House (A. Langley), Littlehampton; University Hospital Lewisham (N.D. Pandita-Gunawardena), Lewisham, London; and St James Hospital (F. Hogg and J. Damms), Portsmouth, UK.
Address correspondence and reprint requests to Dr. Clive Holmes, University of Southampton, Clinical Neurosciences Research Division, Memory Assessment and Research Centre, Moorgreen Hospital, Botley Rd., Southampton, UK; e-mail: c.holmes{at}soton.ac.uk
Objective: To determine the efficacy of donepezil in the treatment of neuropsychiatric symptoms in patients with Alzheimer disease (AD) in a randomized withdrawal study.
Method: Patients with mild to moderate AD with marked neuropsychiatric symptoms at baseline (Neuropsychiatric Inventory [NPI] > 11 points) were treated openly with donepezil 5 mg daily for 6 weeks followed by 10 mg daily for a further 6 weeks. Patients were then randomized (60:40) to either placebo or 10 mg donepezil daily. All patients were assessed at 6 weeks and provided there was no marked cognitive deterioration their blinded treatment was continued for a further 6 weeks. NPI and carer distress were assessed at 6 weekly intervals throughout the study.
Results: A total of 134 patients participated. Following randomization patients who continued on donepezil 10 mg for 12 weeks had improvements in NPI compared with the placebo group (mean change –2.9 vs 3.3 points; ITT-LOCF p = 0.02) and in NPI-Distress scores (median change –2.0 vs 1.0 points; ITT-LOCF p = 0.01). During the open-label phase the total NPI and NPI-Distress scores were lower after 12 weeks treatment with open label donepezil compared with baseline (total NPI 22 points vs13 points; ITT-LOCF p < 0.0001; NPI-Distress 13.5 vs 7.9 points; ITT-LOCF p < 0.0001). In the open-label phase all domains of the NPI (with the exception of elation) were improved (all p < 0.05 after Bonferroni correction).
Conclusions: Donepezil has significant efficacy in the treatment of neuropsychiatric symptoms in patients with mild to moderate AD.
Received January 5, 2004. Accepted in final form March 23, 2004.
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