Open-Label Extension Trial Supports Long-Term Use of Viloxazine ER in Children and Adolescents

Viloxazine ER (viloxazine extended-release capsules) is a selective norepinephrine transporter inhibitor and non-stimulant that is FDA-approved for the treatment of pediatric (≥6 years of age) and adult ADHD.¹ A phase 3 open-label extension (OLE) trial evaluated the long-term safety (primary endpoint) and efficacy (secondary endpoint) of viloxazine ER for children (aged 6-11 years) and adolescents (aged 12-18 years) with ADHD.²  

Trial Design and Findings 

Children and adolescents who completed previous randomized, double-blind, placebo-controlled phase 2 or 3 trials of viloxazine ER were eligible to continue in the OLE.² Of 1100 participants enrolled, 646 were children and 454 were adolescents; of these, 635 children and 445 adolescents had at least one efficacy assessment.² The mean and median exposure to viloxazine ER was 428 and 260 days, respectively.² Of note, consistent with the typical nature of OLE trials, this study was not placebo-controlled, and participants entered from lead-in trials with varied or no exposure to viloxazine ER.² 

Altogether, viloxazine ER had a favorable long-term safety profile.² Common treatment-emergent adverse events included nasopharyngitis (9.7%), somnolence (9.5%), headache (8.9%), decreased appetite (6.0%), and fatigue (5.7%).² Severe adverse events were uncommon and only reported in 3.9% of participants.² Meaningful changes in clinical laboratory evaluations, vital signs, physical examinations, or electrocardiograms were rare, and only 2 participants discontinued the trial due to adverse events in these categories (1 child experiencing tachycardia and 1 adolescent experiencing weight decrease).² Overall, adverse events led to withdrawal from the OLE trial in 8.2% of participants, and no new safety concerns were reported.²  

The secondary endpoint of the OLE was to evaluate efficacy outcomes.² Long-term viloxazine ER treatment resulted in sustained improvement in ADHD symptoms, as evaluated by the ADHD Rating Scale (ADHD-RS-IV or ADHD-RS-5), consistent with the version used in each participant’s lead-in trial.² In the OLE, change from baseline scores were consistently lower than the change score at the end of the lead-in trials,² suggesting durable ADHD symptom control with continued, long-term treatment. Hyperactivity/impulsivity and inattention symptoms of ADHD, as measured by ADHD-RS-IV/5 subscales, also improved from the double-blind trial baseline scores and remained consistently lower throughout the OLE.² Efficacy of long-term viloxazine ER treatment was also assessed with the Clinical Global Impression-Improvement (CGI-I) score.² Mean CGI-I scores improved throughout the OLE, consistent with results determined by the ADHD-RS-IV/5 scales.² 

A Safe and Effective Alternative 

The results from this OLE support the long-term safety and efficacy of viloxazine ER for the treatment of pediatric ADHD. As a non-stimulant, viloxazine ER may be advantageous in pediatric populations in which there may be concerns about access restrictions or misuse of stimulant medications. Given the chronic nature of ADHD, findings from this OLE indicate that viloxazine ER may be a promising option for sustained ADHD symptom management in appropriate patients.  

References 

1. Qelbree (viloxazine extended-release capsules) [prescribing information]. Supernus Pharmaceuticals, Inc; 2025. Accessed April 3, 2026.  https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/211964s013lbl.pdf
2. Findling RL, Katic A, Liebowitz M, et al. Viloxazine extended-release capsules in children and adolescents with attention-deficit/hyperactivity disorder: results of a long-term, phase 3, open-label extension trial. CNS Drugs. 2025;39(11):1157-1172. doi:10.1007/s40263-025-01209-0