Donepezil for treatment of cognitive dysfunction in children with Down syndrome aged 10-17.
The objective of this 10-week, randomized, double-blind, placebo-controlled multicenter study was to assess the efficacy and safety of donepezil for the treatment of cognitive dysfunction exhibited by children with Down syndrome (DS). Intervention comprised donepezil (2.5-10 mg/day) in children (aged 10-17 years) with DS of mild-to-moderate severity. The primary measures were the Vineland-II Adaptive Behavior Scales (VABS-II) Parent/Caregiver Rating Form (PCRF) the sum of nine subdomain standardized scores and standard safety measures. Secondary measures included the VABS-II/PCRF scores on the following domains and their respective individual subdomains: Communication (receptive, expressive, and written); Daily Living Skills (personal, domestic, and community); Socialization (interpersonal relationships, play and leisure time, and coping skills), and scores on the Test of Verbal Expression and Reasoning, a subject-performance-based measure of expressive language. At baseline, 129 participants were assigned treatment with donepezil or placebo. During the double-blind phase, VABS II/PCRF sum of the nine subdomain standardized scores, called v-scores, improved significantly from baseline in both groups (P < 0.0001), with no significant between-group differences. This trial failed to demonstrate any benefit for donepezil versus placebo in children and adolescents with DS, although donepezil appeared to be well tolerated.
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA. kishn001@mc.duke.edu
Priya S
PS
Kishnani
James H
JH
Heller
Gail A
GA
Spiridigliozzi
Ira
I
Lott
Luis
L
Escobar
Sharon
S
Richardson
Richard
R
Zhang
Thomas
T
McRae
D000293:Adolescent; D001519:Behavior / Q000187:drug effects; D017028:Caregivers / Q000523:psychology; D002648:Child; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology; D003967:Diarrhea / Q000139:chemically induced; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004314:Down Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007858:Learning / Q000187:drug effects; D008297:Male; D009483:Neuropsychological Tests; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D014839:Vomiting / Q000139:chemically induced
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil