Journal of Molecular Neuroscience

, Volume 69, Issue 2, pp 224–234 | Cite as

Improvement of Language in Children with Autism with Combined Donepezil and Choline Treatment

  • Lidia V. GabisEmail author
  • Rotem Ben-Hur
  • Shahar Shefer
  • Ariela Jokel
  • Dorit Ben Shalom


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.


Autism 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

Financial Disclosure

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.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.The Weinberg Child Development Center at Safra Children’s Hospital, Sheba Tel HashomerRamat GanIsrael
  2. 2.Sackler School of Medicine at Tel Aviv UniversityTel Aviv-YafoIsrael
  3. 3.Ben Gurion University of the NegevBe’er ShevaIsrael

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