Affiliations: Autism and Epilepsy Services of Illinois, S.C., S.C.;
Lake Bluff, Illinois, U.S.A.
Note: [] Correspondence: Michael G. Chez, M.D. Director, Autism and
Epilepsy Services of Illinois, S.C. 40 East Scranton P.O. Box 280 Lake Bluff,
Illinois 60044, U.S.A. Tel: (847) 735-0300; fax: (847) 735-0400; E-mail:
mchezmd@sbcglobal.net
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).
