Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease.
OBJECTIVE
This subanalysis of a large, double-blind, placebo-controlled trial examined the prevalence of behavioral symptoms in moderate to severe Alzheimer's disease (AD), and the effect of treatment with donepezil.


METHODS
Two hundred ninety patients with moderate to severe AD (standardized Mini-Mental State Examination scores 5-17) were randomized to receive 24 weeks of once-daily doses of donepezil 5 mg/day for 28 days, and 10 mg/day thereafter per the clinician's judgment (n = 144), or placebo (n = 146). The outcome measure of interest was the 12-item Neuropsychiatric Inventory (NPI).


RESULTS
Baseline demographics were similar between the treatment groups. Least squares mean (+/- SE) baseline NPI 12-item total scores were 19.55 +/- 1.48 and 19.30 +/- 1.45, respectively. At baseline, the most common symptoms were apathy/indifference (67%), aberrant motor behavior (53%), depression/dysphoria (52%), anxiety (49%), and agitation/aggression (45%). NPI individual item change from baseline scores at Week 24 using a last observation carried forward (LOCF) analysis showed benefits with donepezil treatment compared with placebo for all items, with significant treatment differences for depression/dysphoria, anxiety, and apathy/indifference (p < .05). Symptoms present at baseline that improved significantly for donepezil- compared with placebo-treated patients at Week 24 LOCF included anxiety, apathy/indifference, and irritability/lability (p < .05). When patients who were not receiving psychoactive medications at baseline were analyzed separately, significant improvements in NPI (continued) 12-item total score were observed with donepezil compared with placebo at most visits and at Week 24 LOCF (p < .05).


CONCLUSIONS
Behavioral symptoms of the magnitude observed in this moderate to severe AD population improved with donepezil.
Gauthier
Serge
S
Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, Verdun, Quebec, Canada. serge.gauthier@mcgill.ca
Feldman
Howard
H
Hecker
Jane
J
Vellas
Bruno
B
Ames
David
D
Subbiah
Ponni
P
Whalen
Edward
E
Emir
Birol
B
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D001007:Anxiety / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D001143:Arousal / Q000187:drug effects; D003863:Depression / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008609:Mental Status Schedule; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D012920:Social Behavior Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D016896:Treatment Outcome
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil