Efficacy and Safety of SPN-812 (Extended-Release Viloxazine) in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis

Background: SPN-812 has been approved for attention-deficit/hyperactivity disorder (ADHD) treatment in children and adolescents.

Objective: We aimed to analyze the efficacy and safety of different doses of SPN-812 for ADHD pediatric patients of different ages, verify its clinical efficacy, and evaluate its safety.

Methods: Up until 30 August 2023, randomized controlled trials (RCTs) were searched in EMBASE, MEDLINE, the Cochrane Library, and clinicaltrials.gov to evaluate different doses of SPN-812 and a placebo.

Results: We pooled 1619 patients from five RCTs with a duration of 6-8 weeks. Patients (6-17 years old) in SPN-812 (100, 200, and 400 mg/d) groups were superior to the control group in all efficacy outcomes with lower attention-deficit/hyperactivity disorder rating scale-5 (ADHD-RS-5), Conners 3-parent short form composite T score (Conners 3-PS), Weiss functional impairment rating scale-parent (WFIRS-P), and increased clinical global impression-improvement (CGI-I) score (both < 0.05). At the same time, only SPN-812 300 mg/d did not show a significantly high risk of the adverse events (AEs) such as somnolence and decreased appetite ( = 0.09). There was no significant difference between placebo and SPN-812 groups (100, 200, and 400 mg/d) in serious adverse events (SAEs) such as syncope. The subgroup analyses showed that, both in children and adolescents subgroups, SPN-812 showed better efficacy than the placebo. The two age subgroups showed a significantly higher risk of AEs and an insignificant risk of SAEs than the placebo.

Conclusion: At present, SPN-812 (100, 200, and 400 mg/d) is superior to the corresponding control in efficacy measures. However, the safety problem cannot be ignored.