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Background Agitation is a common and distressing symptom in patients with Alzheimer's disease. Cholinesterase inhibitors improve cognitive outcomes in such patients, but the benefits of these drugs for behavioral disturbances are unclear.
Methods We randomly assigned 272 patients with Alzheimer's disease who had clinically significant agitation and no response to a brief psychosocial treatment program to receive 10 mg of donepezil per day (128 patients) or placebo (131 patients) for 12 weeks. The primary outcome was a change in the score on the Cohen–Mansfield Agitation Inventory (CMAI) (on a scale of 29 to 203, with higher scores indicating more agitation) at 12 weeks.
Results There was no significant difference between the effects of donepezil and those of placebo on the basis of the change in CMAI scores from baseline to 12 weeks (estimated mean difference in change [the value for donepezil minus that for placebo], –0.06; 95% confidence interval [CI], –4.35 to 4.22). Twenty-two of 108 patients (20.4%) in the placebo group and 22 of 113 (19.5%) in the donepezil group had a reduction of 30% or greater in the CMAI score (the value for donepezil minus that for placebo, –0.9 percentage point; 95% CI, –11.4 to 9.6). There were also no significant differences between the placebo and donepezil groups in scores for the Neuropsychiatric Inventory, the Neuropsychiatric Inventory Caregiver Distress Scale, or the Clinician's Global Impression of Change.
Conclusions In this 12-week trial, donepezil was not more effective than placebo in treating agitation in patients with Alzheimer's disease. (ClinicalTrials.gov number, NCT00142324
[ClinicalTrials.gov]
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Source Information
From the Medical Research Council (MRC) Neurogeneration Research Centre, Institute of Psychiatry, King's College London, London (R.J.H.); the Centre for Statistics in Medicine, Wolfson College, Oxford (E.J.); the Wolfson Centre for Age Related Disease, King's College London, London (C.G.B.); the Queen Elizabeth Psychiatric Hospital, Birmingham (P.B.); the Institute of Psychiatry, King's College London, London (R.G.B., M.K.); Victoria Hospital, Swindon (R.B.); the Division of Psychiatry, Manchester University, Manchester (A.S.B.); the Memory Assessment and Research Centre, University of Southampton, Southampton (C.H.); the Department of Psychiatry, University of Oxford, Oxford (R.J.); the MRC Biostatistics Unit, University of Cambridge Institute of Public Health, Cambridge (T.J.); the Department of Health Sciences, University of Leicester, Leicester (J.L.); the Institute for Ageing and Health, Newcastle University, Newcastle (J.T.O.); the Nuffield Department of Medicine, John Radcliffe Hospital, Oxford (G.W.); the Kent Institute of Medicine and Health, University of Kent, Canterbury (C.K.); the Research Institute for the Care of the Elderly, Bath (R.W.J.); and the Section of Old Age Psychiatry, Institute of Psychiatry, King's College London, London (J.D., M.R.) — all in the United Kingdom.
Address reprint requests to Prof. Howard at the Medical Research Council Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London, DeCrespigny Park, London SE5 8AF, United Kingdom, or at robert.howard{at}iop.kcl.ac.uk.
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