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.
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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.
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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Appendix 1: Authors
Appendix 1: Authors
|Lidia V. Gabis MD||Weinberg Child Development Center at Safra Children’s Hospital, Sheba Tel Hashomer and Sackler School of Medicine at Tel Aviv University||Author||Initiated and designed the study, examined the patients and drafted the manuscript|
|Rotem Ben-Hur PhD||Weinberg Child Development Center at Safra Children’s Hospital, Sheba Tel Hashomer and Ben Gurion University, Beer-Sheva3||Author||Participated in the design and choices of the clinical tools used, performed language and neuropsychological evaluations, conducted the statistical analysis and drafted the manuscript|
|Shahar Shefer PhD||Weinberg Child Development Center at Safra Children’s Hospital, Sheba Tel Hashomer||Author||Participated in the design and study ethics approvals, supervised the evaluations|
|Ariela Jokel PhD||Weinberg Child Development Center at Safra Children’s Hospital, Sheba Tel Hashomer||Author||Helped to design and administer the study tools|
|Dorit Ben Shalom PhD||Ben Gurion University, Beer-Sheva3||Author||Helped in design, analysis, supervision and review of the manuscript|
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Gabis, L.V., Ben-Hur, R., Shefer, S. et al. Improvement of Language in Children with Autism with Combined Donepezil and Choline Treatment. J Mol Neurosci 69, 224–234 (2019). https://doi.org/10.1007/s12031-019-01351-7