Viloxazine for Attention-Deficit Hyperactivity Disorder: A Systematic Review and Meta-analysis of Randomized Clinical Trials

BACKGROUND: Recently, the United States Food and Drug Administration (USFDA) approved viloxazine extended-release (ER) to manage attention-deficit hyperactivity disorder (ADHD) in pediatric patients of 6–17 years of age. OBJECTIVE: To perform a meta-analysis to determine the safety and efficacy of viloxazine ER in the management of ADHD. DATA SOURCE AND METHODS: A literature search was performed through the databases Cochrane Library, PubMed, and clinicaltrials.gov, for a period from inception to August 2021, with the keywords: viloxazine, SPN-812, ADHD, and randomized clinical trials. The randomized controlled trials published in English language that analyzed the efficacy and safety were included. The risk of bias (RoB) was assessed by RoB tool. The outcomes included in this study were the proportion of patients with a 50% reduction in ADHD-Rating Scale-5 (ADHD-RS-5 responders) and improvement in CGI-I scale and the proportion of patients with at least one adverse event, the incidence of somnolence and Serious Adverse Events (SAEs). RESULTS: This meta-analysis includes 1605 patients from five randomized clinical trials; all of the trials were at low risk of bias. Viloxazine group had more ADHD-RS-5 responders as compared to placebo; RR = 1.62; 95% CI = 1.36-1.93; P = <.00001. Significantly higher number of patients showed improved CGI-I score; RR = 1.53; 95% CI = 1.32-1.78; P = <.00001. A higher proportion of patients was observed with at least one adverse event (RR = 1.52; 95% CI = 1.24-1.85; P = <.0001), and somnolence (RR = 3.93; 95% CI = 2.11-7.31; P = <.0001) in viloxazine group. The incidence of SAEs was more in viloxazine group (RR = 2.98; 95% CI = .67-13.3; P = .15). CONCLUSIONS: Viloxazine was found to be significantly superior to placebo in both efficacy outcomes. Adverse events and somnolence were significantly more than the placebo. The incidence was SAEs was more in the viloxazine group but was not statistically significant.