Efficacy and Tolerability of Viloxazine Compared to Placebo on Emotional, Behavioral, and Executive Functioning in Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) can lead to significant long-term consequences, including emotional and behavioral problems, in addition to difficulties with executive function. While stimulant medications are commonly used to treat ADHD, concerns about the risk of drug abuse have led to interest in non-stimulant options including viloxazine. This study aims to evaluate the effectiveness of viloxazine in improving emotional, behavioral, and executive function in children and adolescents with ADHD, focusing on age-related differences in treatment outcomes, symptom presentation, and medication tolerability to inform tailored approaches to treatment. Methods: This systematic review assesses the effectiveness of viloxazine in children and adolescents with ADHD. A comprehensive search of electronic databases, including Cochrane Controlled Trials Register, CINAHL, ClinicalTrials.gov, Embase, PubMed, and Scopus, was conducted for randomized controlled trials (RCTs) published by May 4, 2024. Studies were included if they reported mean changes in emotional and behavioral problems and executive function. The review was registered under PROSPERO ID CRD42022302673. Results: Viloxazine consistently improved emotional, behavioral, and executive function in children with ADHD, with similar but less consistent trends observed in adolescents. Both age groups experienced side effects such as somnolence, decreased appetite, and fatigue, necessitating careful monitoring to enhance tolerability and reduce dropout rates. Discussion: The limited number of eligible RCTs presents challenges in drawing definitive conclusions. While viloxazine shows the potential to improve ADHD symptoms and executive functioning, its acceptability and tolerability vary between children and adolescents. Further research is essential to explore the long-term safety and efficacy of viloxazine, particularly in adolescents, and to more completely understand the mechanisms of its action. Future studies should also compare viloxazine with other non-stimulant treatments to optimize ADHD management strategies.