Effects of Donepezil on clinical symptoms, language, and executive skills in individuals with Autism Spectrum Disorder: A systematic review

Background. This study assessed the potential efficacy of donepezil in treating autism spectrum disorder (ASD), a neurodevelopmental condition characterized by social communication difficulties and repetitive behaviors. Donepezil, primarily used to treat Alzheimer’s disease as an acetylcholinesterase inhibitor, has gained attention as a potential treatment for ASD symptoms. Methods. Following PRISMA guidelines, a systematic review was conducted to investigate the effects of donepezil on individuals with ASD. Outcome measures assessed various aspects of ASD, including language skills, executive function, behavior, and core symptoms. Nine studies were identified, including four randomized controlled trials (RCTs), three retrospective studies, one open-label trial, and one case report. Results. One RCT reported significant improvements in expressive and receptive language skills, especially in younger children. Another study combining donepezil with choline supplementation showed enhanced receptive language skills, particularly in younger participants. An open-label trial indicated improved rapid eye movement sleep patterns in autistic children treated with donepezil. Several retrospective studies reported improvements in behavioral symptoms, such as aggression and hyperactivity. However, other RCTs did not find statistically significant improvements in executive functioning. Conclusion. In general, donepezil use in ASD demonstrates promise in specific areas, notably language development and behavioral symptom management. However, the results are contradictory, requiring further research to clarify its role, optimal dosing, long-term effects, and potential side effects in individuals with ASD. Practical Implications. Donepezil can be used to improve the clinical global impression and language skills of people with ASD.