Evaluating the Effectiveness of Adding N-acetylcysteine to the Risperidone Treatment Regimen in Patients With Autism Disorders

Introduction: Autism spectrum disorder (ASD) has been defined as a group of neurodevelopmental disorders with variable degrees of behavioral and mental problems. Although there is no definite treatment for ASD, antipsychotics are among the available treatments. Recent clinical trials are evaluating the effectiveness of combination therapy of antipsychotics and other drugs, including N-acetylcysteine (NAC). However, the effectiveness of such a combination is controversial across different studies and here we add NAC to the risperidone regimen of ASD patients and evaluate their behavioral outcomes. Methods: Overall, 66 pediatric patients with the psychiatric disorder of ASD, as per the DSM-5 guidelines, were selected from patients referred to Dr. Sheikh and Ibn Sina hospitals (Mashhad City, Iran) from September 2019 to March 2020. Patients who were not receiving risperidone for at least one month were not included. The study population was divided into equal groups and followed for 10 weeks. Risperidone (0.5 to 2 mg/d) and 600 mg of NAC (one tablet per day) were administered to the case group. The control group was given a similar dose of risperidone and a placebo tablet. The Persian version of the clinical global impression (CGI) questionnaire, clinical autism rating scale (CARS), and the national drug side effect checklist were completed in every follow-up visit, and the changes in CGI and CARS scores were compared among the study groups. Results: The mean age of included patients (19 girls, 28.8%, and 47 boys, 71.2%) was 5.89±1.38 years. Among the CARS domains, significant group and time*group interaction effects were observed on fear and nervousness (P=0.002 and P=0.002, respectively), verbal communication (P<0.001 and P=0.005, respectively), non-verbal communication (P<0.001 and P=0.001, respectively), and significant time, group, and time*group interaction effects for general impression (P=0.001, P<0.001, P=0.012, respectively). There was a notable group effect for CGI total score (P=0.002). Conclusion: Adding NAC to the risperidone treatment regimen improved the management of fear and nervousness, verbal and non-verbal communication skills, as well as a general impression in pediatric patients with ASD.