Donepezil for treatment of cognitive dysfunction in children with Down syndrome aged 10–17

Abstract

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.

Outcome Measures for Clinical Trials in Down Syndrome

“…In particular, survey interview forms from these tests were preferred for clinical trials to reduce potential placebo effects. Further, these two scales are suitable for a wide age range, maintain good psychometric properties, and the scales have already been used in trials with people with DS (Boada et al, 2012; Kishnani et al, 2010). In addition, maladaptive domains, which are key in this population (see section on Maladaptive Behavior) can be examined with these two scales.…”

Is it possible to improve neurodevelopmental abnormalities in Down syndrome?

“…Consequently, recommendations cannot be made for DS regarding these drugs. A very recent article (Kishnani et al, 2010 ) reports the results of a clinical trial with 129 participants (children aged 10 -17 years) who received donepezil or a placebo for 10 weeks. This trial failed to demonstrate any benefi t of donepezil compared to a placebo in children and adolescents with DS.…”

A ‘cure’ for Down syndrome: what do parents want?

“…Clinical trials investigating the effects of donepezil pharmacotherapy on learning and memory have shown mixed results [2][3][4][5][6] . More recently, mouse models have provided valuable insights [7][8][9][10] into the pathogenesis underlying DS, which have led to novel targets for pharmacologic interventions [11][12][13] .…”