title: Preliminary study of the safety and efficacy of donepezil hydrochloride in children with Down syndrome: a clinical report series.
abstract: There is growing evidence to support the use of early central cholinergic enhancement to improve cognitive functioning in individuals with Down syndrome (DS). This report summarizes preliminary safety and cognitive efficacy data for seven children (8-13 years) with DS who participated in a 22-week, open-label trial of donepezil hydrochloride. Donepezil was dosed once daily at 2.5 mg and, based on tolerability, increased to 5 mg/day. Safety assessments were conducted at Week 1 (baseline), Week 8 (2.5 mg donepezil), Week 16 (5 mg) and Week 22 (after the donepezil had been discontinued). Measures of cognitive function were administered at each visit, encompassing the following domains: memory; attention; mood; and adaptive functioning. Donepezil was well tolerated at the 2.5 and 5 mg doses. The side effects were mild, transient, and consistent with the adverse events noted with cholinesterase inhibitors. Some children showed improvement on measures of memory (NEPSY Memory for Names and Narrative Memory) and sustained attention to tasks (Conners' Parent Rating Scales), although increased irritability and/or assertiveness were noted in some patients. Overall, this clinical report series adds to our initial findings of language gains in children with DS treated with donepezil. It also supports the need for larger, double-blind studies of the safety and efficacy of donepezil and other cholinesterase inhibitors for children with DS.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA. spiri001@mc.duke.edu
authors.forename: Gail A
authors.initials: GA
authors.lastname: Spiridigliozzi
authors.forename: James H
authors.initials: JH
authors.lastname: Heller
authors.forename: Blythe G
authors.initials: BG
authors.lastname: Crissman
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Sullivan-Saarela
authors.forename: Rebecca
authors.initials: R
authors.lastname: Eells
authors.forename: Deborah
authors.initials: D
authors.lastname: Dawson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Li
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
mesh_terms: D000293:Adolescent; D002648:Child; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D000077265:Donepezil; D004314:Down Syndrome / Q000175:diagnosis / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil