Donepezil hydrochloride: a double-blind study in autistic children

Abstract

Recent studies in autistic brain samples have shown diminished acetylcholine and nicotinic receptor activity. We hypothesized that acetylcholinergic enhancement may pharmacologically improve some autistic characteristics. Donepezil hydrochloride, an acetylcholinesterase inhibitor, was studied previously in two open label studies which showed improvement in the expressive and receptive speech and aberrant behaviors of autistic children. We therefore undertook a double-blind placebo controlled study to confirm these findings. Forty-three patients (35 males, 8 females, average age 6.8 yrs., range 2.1–10.3 yrs), with diagnoses of Autistic Spectrum Disorders enrolled in a randomized six-week, doubleblind, placebo-controlled trial of donepezil hydrochloride, with an additional six weeks of open-label treatment. Change was evaluated by the Childhood Autistic Rating Scale, Gardner’s Expressive One-Word Picture Vocabulary Test, Revised, and Gardner’s Receptive One-Word Picture Vocabulary Test. Testing was administered at baseline, six-week, and twelveweek follow-up. Expressive and receptive speech gains, as well as decreases in severity of overall autistic behavior, were documented after 6-weeks for the treatment group. These improvements were statistically significant when compared to placebo, and were clinically meaningful as assessed over time. Donepezil hydrochloride appears to improve expressive and receptive language as well as overall autistic features, consistent with the hypothesis of acetylcholinergic enhancement. (J Pediatr Neurol 2003; 1(2): 83–88).