Elbeltagi YM, Abd Rab El Rasool AO, Elkashlan AM, Al-Beltagi M. Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges. World J Clin Pediatr 2026; 15(2): 117274 [DOI: 10.5409/wjcp.v15.i2.117274]
Corresponding Author of This Article
Mohammed Al-Beltagi, MD, PhD, Professor, Senior Researcher, Department of Pediatrics, Faculty of Medicine, Tanta University, 1 Hassan Radwan Street, Tanta 31511, Algharbia, Egypt. mohamed.elbeltagi@med.tanta.edu.eg
Research Domain of This Article
Pediatrics
Article-Type of This Article
Systematic Reviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Jun 9, 2026 (publication date) through May 16, 2026
Times Cited of This Article
Times Cited (0)
Journal Information of This Article
Publication Name
World Journal of Clinical Pediatrics
ISSN
2219-2808
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Elbeltagi YM, Abd Rab El Rasool AO, Elkashlan AM, Al-Beltagi M. Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges. World J Clin Pediatr 2026; 15(2): 117274 [DOI: 10.5409/wjcp.v15.i2.117274]
World J Clin Pediatr. Jun 9, 2026; 15(2): 117274 Published online Jun 9, 2026. doi: 10.5409/wjcp.v15.i2.117274
Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges
Yousif M Elbeltagi, Ahmed Osama Abd Rab El Rasool, Ahmed Mohammed Elkashlan, Mohammed Al-Beltagi
Yousif M Elbeltagi, Department of Medicine, The Royal College of Surgeons in Ireland - Bahrain, Busaiteen 15503, Muharraq, Bahrain
Ahmed Osama Abd Rab El Rasool, Department of Neuropsychiatry, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
Ahmed Mohammed Elkashlan, Department of Medicine, Faculty of Medicine, Tanta University, Tanta 31511, Algharbia, Egypt
Mohammed Al-Beltagi, Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Algharbia, Egypt
Mohammed Al-Beltagi, Department of Paediatrics, University Hospital, Arabian Gulf University, Manama 26671, Bahrain
Co-first authors: Yousif M Elbeltagi and Ahmed Osama Abd Rab El Rasool.
Author contributions: Elbeltagi YM contributed to the conceptualization of the study, executed the literature search, performed the formal analysis (including the meta-analytic calculations), and participated in writing the original draft of the manuscript; Elbeltagi YM and Elkashlan AM contributed to the data curation; Abd Rab El Rasool AO contributed to the methodology, assisted with data extraction and qualitative synthesis, and critically reviewed and edited sections of the manuscript, particularly those related to neuropsychiatry; Elkashlan AM contributed to validation of the extracted clinical data, participated in the writing of the original draft (specifically the sections on pharmacological agents); Elkashlan AM and Al-Beltagi M critically reviewed the final manuscript; Al-Beltagi M served as the senior author, providing conceptualization and overall supervision of the project, contributed significantly to the methodology design, provided critical intellectual revision, wrote, and edited the final manuscript, and is responsible for the final approval of the submitted version. All authors have read and agreed to the published version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Mohammed Al-Beltagi, MD, PhD, Professor, Senior Researcher, Department of Pediatrics, Faculty of Medicine, Tanta University, 1 Hassan Radwan Street, Tanta 31511, Algharbia, Egypt. mohamed.elbeltagi@med.tanta.edu.eg
Received: December 3, 2025 Revised: December 13, 2025 Accepted: February 24, 2026 Published online: June 9, 2026 Processing time: 161 Days and 12.6 Hours
Abstract
BACKGROUND
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition associated with debilitating comorbidities [e.g., aggression, irritability, gastrointestinal (GI) issues]. Medical management primarily targets these symptoms, as no drug is Food and Drug Administration-approved for core social-communication deficits.
AIM
To synthesize the efficacy and safety of five major pharmacological classes and evaluate the emerging evidence for biomarker-driven (precision medicine) interventions in pediatric ASD.
METHODS
Following PRISMA guidelines, we systematically reviewed randomized controlled trials (RCTs) for five classes: Atypical antipsychotics, stimulants, selective serotonin reuptake inhibitors, metabolic/nutritional, and microbiota-gut-brain axis agents. Quantitative meta-analysis for antipsychotics (n = 5 RCTs pooled) used the random-effects model, reporting I2 to quantify heterogeneity.
RESULTS
Atypical antipsychotics are the only drugs with robust, established efficacy for severe irritability: Pooled analysis for risperidone (n = 3 RCTs) showed a significant mean difference of approximately -11.0 on Aberrant Behavior Checklist-Irritability subscale (I2 approximately 72%). Risperidone carries a greater metabolic burden (e.g., weight gain) than aripiprazole. Stimulants and selective serotonin reuptake inhibitors, respectively. Emerging therapies demonstrate targeted potential: Microbiota transfer therapy significantly improved GI and behavioral symptoms in cohorts with GI disease. Similarly, the efficacy of High-dose folinic acid was concentrated in the subgroup with folate receptor-α autoantibodies.
CONCLUSION
The management of ASD demands a shift to a precision medicine model, as the efficacy of interventions is highly variable and concentrated in specific patient subgroups. Future research must prioritize the validation of biological biomarkers (metabolic, genetic, neurophysiological) to reliably predict treatment response, guiding the selection of targeted therapies, and addressing current evidence gaps.
Core Tip: The core finding of this systematic review is that the medical management of autism spectrum disorder is primarily focused on controlling debilitating comorbid symptoms (e.g., aggression, gastrointestinal distress) rather than improving core social deficits, for which no medication is approved. The field is rapidly transitioning from a broad, empirical treatment approach to one of precision medicine. This shift is driven by evidence that highly targeted interventions, such as microbiota transfer therapy for children with gastrointestinal abnormalities.
