Improvement of Language in Children with Autism with Combined Donepezil and Choline Treatment
The safety and efficacy of a novel combination treatment of AChE inhibitors and choline supplement was initiated and evaluated in children and adolescents with autism spectrum disorder (ASD). Safety and efficacy were evaluated on 60 children and adolescents with ASD during a 9-month randomized, double-blind, placebo-controlled trial comprising 12 weeks of treatment preceded by baseline evaluation, and followed by 6 months of washout, with subsequent follow-up evaluations. The primary exploratory measure was language, and secondary measures included core autism symptoms, sleep and behavior. Significant improvement was found in receptive language skills 6 months after the end of treatment as compared to placebo. The percentage of gastrointestinal disturbance reported as a side effect during treatment was higher in the treatment group as compared to placebo. The treatment effect was enhanced in the younger subgroup (younger than 10 years), occurred already at the end of the treatment phase, and was sustained at 6 months post treatment. No significant side effects were found in the younger subgroup. In the adolescent subgroup, no significant improvement was found, and irritability was reported statistically more often in the adolescent subgroup as compared to placebo. Combined treatment of donepezil hydrochloride with choline supplement demonstrates a sustainable effect on receptive language skills in children with ASD for 6 months after treatment, with a more significant effect in those under the age of 10 years.
KeywordsAutism Language Donepezil Choline Children
The authors acknowledge the following:
Solgar Inc. for donating choline supplement.
Unipharm for a discount on donepezil hydrochloride tablets.
Research assistants: Maayan Farkash and Idan Sarig.
Leora Allen for English editing.
All the families who participated in this trial.
The study was funded by local associations—the Israeli Society of Clinical Pediatrics (HIPAK) and MATERNA.
Compliance with Ethical Standards
The authors have no financial relationships relevant to this article to disclose.
Conflict of Interest
The authors declare that they have no conflict of interest.
- Blusztajn JK, Slack BE, Mellott TJ (2017) Neuroprotective actions of dietary choline. Nutrients 9Google Scholar
- Busner J, Targum SD (2007) The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont) 4(7):28–37Google Scholar
- Chez MG, Buchanan TM, Becker M, Kessler J, Aimonovitch MC, Mrazek SR (2003) Donepezil hydrochloride: a double-blind study in autistic children. J Pediatr Neurol 1(2):83–88Google Scholar
- Kaufman AS, Kaufman NL (2014) Kaufman brief intelligence test, second edition. In: Encyclopedia of special educationGoogle Scholar
- Lord C, Rutter M, Dilavore P, Risi S (2001) Autism diagnostic observation schedule, manual. Western psychological services, Los Angeles. 1–3 pGoogle Scholar
- Rimland B, Edelson SM Autism treatment evaluation checklist (ATEC) [internet]. 2018 [cited 2018 Feb 5]. Available from: https://www.autism.com/ind_atec
- Sparrow SS, Cicchetti DV, Balla DA (2005) Vineland adaptive behavior scale, second edition, survey forms manual. NCS Pearson, Inc, pp 1–78Google Scholar
- Wechsler D (2004) The Wechsler intelligence scale for children—fourth edition. The Wechsler intelligence scale for children—fourth edition. 153–190 pGoogle Scholar
- Zimmerman IL, Steiner VG, Pond RE (2002) Preschool language scale fourth edition; Examiner’s manual, Harcourt assessment, pp 2–6Google Scholar