Safety and Efficacy of Donepezil in Children and Adolescents with Autism: Neuropsychological Measures

Abstract

Objective: There has been recent interest in the use of cognitive enhancing drugs, such as cholinesterase inhibitors, as a possible treatment for executive functioning (EF) deficits in autism spectrum disorder (ASD). The goal of this study was to assess the tolerability, safety, and efficacy of donepezil on EF in a sample of children and adolescents with ASD. Method: Thirty-four children and adolescents with ASD (age range 8-17 years; IQ >75) were enrolled in a 10-week, doubleblind, placebo-controlled trial of donepezil (doses of 5 and 10 mg), followed by a 10-week open label trial for placebo nonresponders. Results: The effect of donepezil treatment on EF was examined. Despite improvement on a number of EF measures, no statistically significant between-group differences were found (with gains observed for both the placebo and donepezil groups). Conclusions:The results suggest that short-term treatment with donepezil may have limited impact on cognitive functioning in ASD. Future controlled trials may need to consider a longer treatment period to detect significant gains on EF measures.

Acetylcholine Elevation Relieves Cognitive Rigidity and Social Deficiency in a Mouse Model of Autism

“…Hence, we suggest that future clinical trials with AChEIs will assess the correlation between circumscribed interests and social interference in ASD patients. Clinical studies of this correlation may also close the gap between the clear-cut results of the current study and the only tenuous clinical effects (Handen et al, 2011).…”

“…In two open-label (Buckley et al, 2011;Hardan and Handen, 2002) and one case-study (Srivastava et al, 2011), the drug was found useful in reducing overall ASD severity. Two double-blind placebo-controlled studies were conducted (Chez et al, 2003;Handen et al, 2011), showing amelioration in ASD symptoms after treatment with the drug. However, between-groups data were not analyzed (Chez et al, 2003) or were not statistically significant (Handen et al, 2011).…”

“…Two double-blind placebo-controlled studies were conducted (Chez et al, 2003;Handen et al, 2011), showing amelioration in ASD symptoms after treatment with the drug. However, between-groups data were not analyzed (Chez et al, 2003) or were not statistically significant (Handen et al, 2011). Hence, the potential therapeutic effects of Donepezil on ASD symptoms in human patients are suggestive yet not conclusive (Handen et al, 2011).…”

“…However, between-groups data were not analyzed (Chez et al, 2003) or were not statistically significant (Handen et al, 2011). Hence, the potential therapeutic effects of Donepezil on ASD symptoms in human patients are suggestive yet not conclusive (Handen et al, 2011).…”

Placebo-Controlled Pilot Trial of Mecamylamine for Treatment of Autism Spectrum Disorders

“…However, a controlled trial showed equivocal results (Handen et al 2010(Handen et al , 2011). Cholinesterase inhibitors increase the level of acetylcholine and activate both muscarinic and nAChRs.…”