A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer's disease--pilot study.
BACKGROUND
Donepezil Hydrochloride (Aricept) is a selective anticholinesterase inhibitor developed for the treatment of Alzheimer's disease (AD). This study investigated the safety and efficacy of the drug to treat Down syndrome (DS) adults with mild to moderate AD.


METHODS
This was a 24-week, double blind, placebo controlled, parallel-group trial. Patients were randomized to receive placebo or donepezil (5 mg per day during the first four weeks, and then 10 mg per day thereafter). Primary efficacy was measured using the Dementia Scale for Mentally Retarded Persons (DMR), and secondary efficacy was measured using the Severe Impairment Battery (SIB), Neuropsychiatric Inventory (NPI) and by the Adaptive Behavior Scale (ABS).


RESULTS
A total of 30 DS patients with AD entered the study of which 27 were included in the subsequent data analysis. The donepezil group had non-statistically significant reduction in deterioration in DMR, SIB, and ABS mean scores relative to the placebo group. However NPI scores showed less improvement in the donepezil group when compared to the placebo group. Fifty percent of subjects in the donepezil group showed improvement in mean DMR scores at the end point compared to baseline, when compared to 31% on placebo. There were no life threatening adverse effects associated with treating adults with DS with donepezil. A number of side-effects did occur including diarrhoea, insomnia, fatigue, and nausea.


CONCLUSIONS
Donepezil Hydrochloride administered once a day appears to be generally well tolerated and safe in DS adults who have AD. There is some possible efficacy in the treatment of symptoms of mild to moderate Alzheimer's disease in this population, although the sample size of this study was too small for statistical significance. It is recommended that donepezil, with the appropriate precautions, should be considered for the treatment of AD in adults with DS as deemed by a specialist.
Prasher
Vee P
VP
Monyhull Hospital, Monyhull Hall Road, Kings Norton, Birmingham, B30 3QB, UK. vprasher@compuserve.com
Huxley
Adam
A
Haque
M S
MS
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015897:Comorbidity; D000077265:Donepezil; D004311:Double-Blind Method; D004314:Down Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil