Donepezil in Parkinson's disease dementia: a randomized, double-blind efficacy and safety study.
Parkinson's disease dementia (PDD) is associated with cholinergic deficits. This report presents an efficacy and safety study of the acetylcholinesterase inhibitor donepezil hydrochloride in PDD. PDD patients (n = 550) were randomized to donepezil (5 or 10 mg) or placebo for 24 weeks. Coprimary end points were the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+; global function). Secondary end points measured executive function, attention, activities of daily living (ADLs), and behavioral symptoms. Safety and tolerability were assessed. ADAS-cog mean changes from baseline to week 24 (end point) were not significant for donepezil in the intent-to-treat population by the predefined statistical model (difference from placebo: -1.45, P = .050, for 5 mg; -1.45, P = .076, for 10 mg). Alternative ADAS-cog analysis, removing the treatment-by-country interaction term from the model, revealed significant, dose-dependent benefit with donepezil (difference from placebo: -2.08, P = .002, for 5 mg; -3.31, P < .001, for 10 mg). The 10-mg group, but not the 5-mg group, had significantly better CIBIC+ scores compared with placebo (3.7 vs 3.9, P = .113, for 5 mg; 3.6 vs 3.9, P = .040, for 10 mg). Secondary end points-Mini-Mental State Exam; Delis-Kaplan Executive Function System; Brief Test of Attention, representing cognitive functions particularly relevant to PDD-showed significant benefit for both donepezil doses (P ≤ .007). There were no significant differences in ADLs or behavior. Adverse events were more common with donepezil but mostly mild/moderate in severity. Although the study did not achieve its predefined primary end points, it presents evidence suggesting that donepezil can improve cognition, executive function, and global status in PDD. Tolerability was consistent with the known safety profile of donepezil. © 2012 Movement Disorder Society.
Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), UMR-S975, France. bruno.dubois@psl.aphp.fr
Bruno
B
Dubois
Eduardo
E
Tolosa
Regina
R
Katzenschlager
Murat
M
Emre
Andrew J
AJ
Lees
Günther
G
Schumann
Emmanuelle
E
Pourcher
Julian
J
Gray
Gail
G
Thomas
Jina
J
Swartz
Timothy
T
Hsu
Margaret L
ML
Moline
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003704:Dementia / Q000150:complications / Q000188:drug therapy*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy*; D010880:Piperidines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil