Viloxazine
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Viloxazine: From Narcolepsy to Attention Deficit Hyperactivity Disorder
One-Sentence Summary
Viloxazine is listed in the knowledge graph as originally associated with narcolepsy-related indications, although in the US it is marketed as an extended-release product (Qelbree) for ADHD. The TxGNN model predicts it may be effective for attention deficit-hyperactivity disorder, with 5 clinical trials and 19 publications currently supporting this direction. Note that ADHD is already an FDA-approved use of extended-release viloxazine, so this is not a repurposing candidate in the strict sense.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Narcolepsy, narcolepsy-cataplexy syndrome, narcolepsy without cataplexy (from the knowledge graph; no approved indication text in the US licence record) |
| Predicted New Indication | Attention deficit-hyperactivity disorder |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L1 |
| US Market Status | Cancelled only |
| Number of NDAs | 1 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, viloxazine is a selective norepinephrine reuptake inhibitor with additional serotonergic modulation. This is consistent with the noradrenergic mechanism of other non-stimulant ADHD treatments such as atomoxetine.
The original narcolepsy indications and ADHD are both conditions of impaired arousal, attention and wakefulness regulation, in which noradrenergic signalling plays a role. This provides a plausible, though indirect, link between the two.
The strongest support is direct clinical evidence: a placebo-controlled, flexible-dose Phase 3 trial in adults (NCT04016779) and several long-term extension studies. Extended-release viloxazine (Qelbree) is already described in the literature as an FDA-approved nonstimulant for children, adolescents and adults with ADHD. The prediction is therefore confirmed by existing practice rather than being a new discovery.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04016779 | Phase 3 | Completed | 374 | Randomized, double-blind, placebo-controlled, flexible-dose (200–600 mg) study of SPN-812 in adults aged 18–65 with ADHD |
| NCT02736656 | Phase 3 | Active, not recruiting | 1400 | Long-term open-label extension of safety and efficacy in paediatric ADHD |
| NCT04143217 | Phase 3 | Completed | 159 | Open-label, flexible-dose long-term safety and efficacy extension in adults with ADHD |
| NCT06185985 | Phase 4 | Completed | 161 | Open-label decentralized trial of Qelbree in adults with ADHD and mood symptoms |
| NCT01107496 | Phase 1/2 | Completed | 52 | Randomized, double-blind, placebo-controlled safety and tolerability study of immediate-release viloxazine in adults with ADHD |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35615643 | 2022 | Systematic review / meta-analysis | J Cent Nerv Syst Dis | Meta-analysis of randomized trials of viloxazine ER in ADHD, following its FDA approval for ages 6–17 |
| 37166701 | 2023 | Systematic review / meta-analysis | CNS Drugs | Nonstimulant medications in adult ADHD, as monotherapy or adjunct to stimulants |
| 40203844 | 2025 | Network meta-analysis | Lancet Psychiatry | Comparative cardiovascular safety of ADHD medications across children, adolescents and adults |
| 41297970 | 2025 | Umbrella review | BMJ | Benefits and harms of ADHD interventions across the lifespan |
| 40802027 | 2025 | Phase 3 open-label extension | CNS Drugs | Long-term safety and efficacy of viloxazine ER in children and adolescents with ADHD |
| 39373844 | 2024 | Phase 3 open-label extension | CNS Drugs | Long-term safety and continued efficacy of viloxazine ER in adults with ADHD |
| 42207988 | 2026 | Phase 4 open-label trial | J Clin Psychiatry | Viloxazine ER in adults with ADHD and comorbid depression and/or anxiety symptoms |
| 37021356 | 2023 | Review | Ann Pharmacother | Efficacy and safety of viloxazine ER in school-age children and adolescents |
| 38502148 | 2024 | Review | Expert Rev Neurother | Viloxazine ER as an FDA-approved nonstimulant option for children, adolescents and adults |
| 37430151 | 2023 | Comparative study | CNS Drugs | Viloxazine ER compared with atomoxetine for ADHD |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA211964 (cancelled) | QELBREE (Supernus Pharmaceuticals) | Capsule, extended release (oral) | Not stated in the licence record |
Safety Considerations
Please refer to the package insert for safety information.
Of note, the literature compiled for this report mentions that the cardiovascular safety of ADHD medications, including haemodynamic and ECG effects, has been the subject of a recent network meta-analysis (PMID 40203844). Noradrenergic reuptake inhibition may also be associated with insomnia.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: A completed Phase 3 randomized placebo-controlled trial, several long-term extension studies and multiple meta-analyses and reviews support viloxazine in ADHD. However, this is an already established use of the extended-release product, not a true repurposing finding. The US licence record shows only a single NDA with cancelled status, and the safety label data are missing.
To proceed, the following is needed:
- FDA package insert warnings and contraindications (a blocking gap for safety screening)
- Confirmation of the current US marketing and licence status of Qelbree, given that the licence record shows “cancelled” while the literature describes it as FDA-approved
- Detailed mechanism of action data from DrugBank
- Clarification of the link between the original narcolepsy indications and ADHD, since the original indication record does not explain the relationship
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.