Qelbree (viloxazine extended-release capsules) / Supernus Pharma, Knight Therap - LARVOL DELTA

Comparative cardiovascular safety of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. (PubMed, Lancet Psychiatry) - "Practitioners should monitor blood pressure and pulse in patients with ADHD treated with any pharmacological intervention, and not stimulants only. Given the short duration of available randomised controlled trials, new research providing insights on the causal effects of ADHD medications on cardiovascular parameters in the longer term should be funded."

Journal • Retrospective data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Cardiovascular • CNS Disorders • Psychiatry

Viloxazine Extended-Release Administered With Psychostimulants in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: A Phase 4, Open-Label Trial. (PubMed, J Child Adolesc Psychopharmacol) - " Combined treatment with VLX-ER and psychostimulant therapy showed acceptable safety and tolerability, with improvement in morning and evening ADHD behaviors and sleep disturbances relative to stimulant monotherapy. Timing of VLX-ER administration (morning or evening) did not appear to affect safety, drug response, or sleep improvement."

Journal • P4 data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Infectious Disease • Pain • Pediatrics • Psychiatry • Respiratory Diseases • Sleep Disorder

Supernus Announces Label Update for Non-Stimulant ADHD Treatment, Qelbree, Including New Pharmacodynamic Data and Information for Breastfeeding Women (GlobeNewswire) - "Supernus Pharmaceuticals, Inc...announced that the U.S. Food and Drug Administration (FDA) has approved an update for the label for Qelbree (viloxazine extended-release capsules) to include new pharmacodynamic data in Section 12.2. The updated label describes viloxazine’s partial agonist activity at the serotonin 5-HT2C receptor and inhibition of the norepinephrine transporter, reinforcing its multimodal pharmacodynamic profile. The mechanism of action of Qelbree, though unclear, is thought to be through inhibiting the reuptake of norepinephrine. Additionally, the updated label now includes new lactation data for breastfeeding women with attention-deficit/hyperactivity disorder (ADHD), showing that the transfer of Qelbree into breastmilk is low. Qelbree is approved for use in patients ages 6 years and older with ADHD."

FDA event • Attention Deficit Hyperactivity Disorder • CNS Disorders

Nonstimulant Medications for Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. (PubMed, Pediatr Ann) - "The recommended nonstimulant ADHD medications include alpha agonists (eg, guanfacine extended-release [ER], clonidine ER) and norepinephrine reuptake inhibitors (eg, atomoxetine, viloxazine)...[Pediatr Ann. 2025;54(1):e27-e33.]."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Mental Retardation • Pediatrics • Psychiatry

Open-label Safety and Efficacy of SPN-812 (Viloxazine Extended-release Capsule) in Adults With ADHD and Mood Symptoms (clinicaltrials.gov) - P4 | N=750 | Active, not recruiting | Sponsor: Supernus Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Response Trajectories and Temporal Trends of Viloxazine Treatment for Young People With ADHD: A Meta-Analysis. (PubMed, JAMA Netw Open) - "Future studies are warranted to assess the long-term effect of viloxazine. Viloxazine was relatively well tolerated for children and adolescents with ADHD."

Clinical • Journal • Retrospective data • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Pediatrics • Psychiatry

Pharmacological Strategies in ADHD: Focus on Pragmatic Management (AACAP 2024) - "Data on adverse effects and combination therapies were also reviewed. The literature combined with the clinical experience indicates that alterations in the use of traditional stimulants in existing and novel release forms, atomoxetine, viloxazine, alpha agonists, the use of alternative agents, and combinations of medications, can enhance a patient's ADHD response. Pharmacological strategies will be reported for those who: 1) have not responded to traditional agents; 2) manifest side effects; and 3) present with comorbidity(ies). Both empirically derived data and illustrative cases will be used in this pragmatic presentation.PPC, ADHD, PKS"

ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

An Open-Label Extension Study Assessing the Long-Term Safety and Efficacy of Viloxazine Extended-Release Capsules in Adults with Attention-Deficit/Hyperactivity Disorder. (PubMed, CNS Drugs) - P3 | "Long-term viloxazine ER use was well tolerated, with no new long-term safety findings. Improvements in ADHD symptoms and associated measures were sustained throughout trial participation. In total, 73% percent of adult participants in this long-term study used viloxazine ER doses of 400 mg or more during maintenance treatment."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Fatigue • Infectious Disease • Insomnia • Novel Coronavirus Disease • Pain • Psychiatry • Respiratory Diseases • Sleep Disorder

Attention-Deficit/Hyperactivity Disorder in Adults. (PubMed, Am Fam Physician) - "Clinical guidelines recommend a subset of amphetamine and methylphenidate stimulants as first-line pharmacotherapy, which may be more effective when combined with psychotherapy. For adults unable to take stimulants or with concurrent anxiety/depression, options include atomoxetine, viloxazine, and bupropion. To monitor for patient misuse or diversion of stimulants, physicians should consider employing controlled substance agreements and prescription drug monitoring programs."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Depression • Developmental Disorders • Mental Retardation • Mood Disorders • Psychiatry

Quantification of ADHD medication in biological fluids of pregnant and breastfeeding women with liquid chromatography: a comprehensive review. (PubMed, Front Public Health) - "This review aims (1) to compile and critically assess existing research on the transfer of ADHD medications into breast milk and the potential implications for nursing infants and (2) to provide a comprehensive overview and discussion of the literature regarding the quantification of methylphenidate, amphetamine, atomoxetine, viloxazine, guanfacine, clonidine and bupropion in the blood, urine, oral fluid, and breast milk with liquid chromatography...We illustrate the lack of methods to simultaneously monitor multiple ADHD medications as well as the lack of developed methods for breast milk. Finally, we highlight the need for continued research to refine our understanding of medication transfer into breast milk and potential risks, and to develop clinical guidelines to support mothers with ADHD in making informed choices regarding medication use during pregnancy and lactation."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Developmental Disorders • Pediatrics • Psychiatry

Treatment Preferences of Adult Patients with Attention-Deficit/Hyperactivity Disorder - A Discrete Choice Experiment. (PubMed, Patient Prefer Adherence) - "Overall preferences for treatment profiles approximating centanafadine, lisdexamfetamine, atomoxetine, and viloxazine were estimated using adjusted total utilities...Accordingly, a profile resembling that of centanafadine would be preferred by an average patient compared to key competitors due to its favorable safety profile. These findings may help improve treatment decision-making, enhance treatment satisfaction, and foster adherence."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder • Xerostomia

Open-label Study to Evaluate Long-term Safety and Efficacy of SPN-812 (Viloxazine Extended-release Capsule) (clinicaltrials.gov) - P3 | N=1400 | Active, not recruiting | Sponsor: Supernus Pharmaceuticals, Inc. | Trial completion date: Jun 2025 ➔ Sep 2026 | Trial primary completion date: Jun 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Pediatrics • Psychiatry

Development of fluorescence probe for spectrofluorimetric determination of viloxazine hydrochloride in pharmaceutical form and rat plasma; additional pharmacokinetic study. (PubMed, Luminescence) - "This method was adeptly applied in a pharmacokinetic study of viloxazine in rat plasma following a single oral dose (10 mg/kg), yielding a mean peak plasma concentration (Cmax) of 1721 ng/ml, achieved within 1.5 h. Furthermore, the environmental impact of the technique was assessed using two greenness assessment tools, revealing a notable level of eco-friendliness and sustainability."

Journal • PK/PD data • Preclinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • CNS Disorders • Genetic Disorders • Psychiatry

Efficacy and safety of monoamine reuptake inhibitors in attention deficit hyperactivity disorder: A Bayesian network meta-analysis. (PubMed, J Psychiatr Res) - "The drugs showing significant reduction on the ADHD rating scale as compared to placebo are bupropion (SMD: 0.33; 95%CrI: 0.60,-0.059), dasotraline(SMD: 0.49; 95%CrI: 0.82,-0.16), venlafaxine(SMD: 0.71; 95%CrI: 1.3,-0.15), viloxazine(SMD: 0.45; 95%CrI: 0.77,-0.12). Other drugs (centanafadine, duloxetine, edivoxetine, reboxetine, tipepidine, vortioxetine) were no better than placebo in reducing symptom severity of ADHD...Among all, duloxetine (OR:15; 95%CrI:1.8130) showed significantly more treatment-emergent adverse events than methylphenidate. In conclusion, venlafaxine, viloxazine, and bupropion are the most efficacious MRIs for ADHD symptom reduction as compared to placebo with high certainty of evidence."

Journal • Retrospective data • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Current nonstimulant medications for adults with attention-deficit/hyperactivity disorder. (PubMed, Expert Rev Neurother) - "Stimulants, including methylphenidate and amphetamines, are the first-line pharmacological treatment of ADHD in adults...Among other compounds indicated for ADHD in adults, antidepressants sharing at least a noradrenergic or dopaminergic component, including tricyclic compounds, bupropion, and viloxazine, have shown demonstratable efficacy. Evidence is also available for antihypertensives, particularly guanfacine, as well as memantine, metadoxine, and mood stabilizers, while negative findings have emerged for galantamine, antipsychotics, and cannabinoids. While according to clinical guidelines, atomoxetine may serve as the only second-line option in adults with ADHD, several other nonstimulant compounds may be effectively used in order to personalize treatment based on comorbid conditions and ADHD features. Nevertheless, further research is needed to identify and test more personalized treatment strategies for adults with ADHD."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

The role of adrenergic neurotransmitter reuptake inhibitors in the ADHD armamentarium. (PubMed, Expert Opin Pharmacother) - "The authors conducted a PubMed literature search using the following key words: 'ADHD' AND 'adrenergic reuptake inhibitors' OR 'nonstimulants' OR 'atomoxetine' OR 'Viloxazine' OR 'Dasotraline' OR 'Centanafadine' OR 'PDC-1421' OR 'Reboxetine' OR 'Edivoxetine' OR 'Bupropion' OR 'Venlafaxine' OR 'Duloxetine.' They reviewed FDA fact sheets of available medications for safety/tolerability studies and reviewed published clinical studies of these medications for treatment of ADHD. Adrenergic neurotransmitter reuptake inhibitors fit the diverse needs of children and adolescents with ADHD with 1) poor tolerability to stimulants (e.g. due to growth suppression, insomnia, rebound irritability, co-morbid depression, anxiety and tic disorders, substance abuse or diversion concerns), 2) cardiac risks, and/or 3) need for extended duration of action. Their differences in receptor..."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Depression • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder • Substance Abuse • Tic Disorders • Tourette Syndrome

Assessment of centanafadine in adults with attention-deficit/hyperactivity disorder: A matching-adjusted indirect comparison vs lisdexamfetamine dimesylate, atomoxetine hydrochloride, and viloxazine extended-release. (PubMed, J Manag Care Spec Pharm) - P3, P4 | "Safety assessment was limited to rates of adverse events reported in both trials of a given comparison. NCT03605680, NCT03605836, NCT00334880, NCT00190736, and NCT04016779."

Clinical • Journal • ADHD (Impulsive Aggression) • Anorexia • Attention Deficit Hyperactivity Disorder • CNS Disorders • Constipation • Erectile Dysfunction • Fatigue • Gastroenterology • Gastrointestinal Disorder • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder • Xerostomia

Recent advances in pharmacological management of attention-deficit/hyperactivity disorder: moving beyond stimulants. (PubMed, Expert Opin Pharmacother) - "Stimulants, such as amphetamine and methylphenidate, are available in more than two dozen formulations, but all have similar adverse effects and carry a risk of misuse and dependence...Two, including atomoxetine and viloxazine extended-release (ER), are approved by the Food and Drug Administration for the treatment of ADHD in children and adults. Two others, clonidine ER and guanfacine ER, are only approved for children and adolescents in the U.S. Several other compounds are under investigation. Drugs in Phase 3 trials include centanafadine, solriamfetol, and L-threonic acid magnesium salt...Lack of individual drug response and tolerability are reasons many stop treatment. Development of new nonstimulants may offer hope for patients who need medication alternatives."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Behavior Disorders • CNS Disorders • Mental Retardation • Psychiatry

Open-Label Study of SPN-812 Administered With Psychostimulants in Children and Adolescents With ADHD (clinicaltrials.gov) - P4 | N=96 | Completed | Sponsor: Supernus Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed | N=60 ➔ 96 | Trial primary completion date: Sep 2023 ➔ May 2023

Enrollment change • Trial completion • Trial primary completion date • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

From Consensus Statement to Pills to Pixels: New Innovations in Attention-Deficit/Hyperactivity Disorder Care. (PubMed, J Child Adolesc Psychopharmacol) - "Health care professionals should integrate these developments into clinical practice, mindful of individual patient and family needs and preferences. Future research should assess long-term outcomes, cost-effectiveness, and acceptability of these innovations."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Pediatrics • Psychiatry

Treatment Preferences of Adult Patients With Attention-Deficit/Hyperactivity Disorder in Canada: A Discrete Choice Experiment (ISPOR 2024) - "Overall preferences for treatment profiles approximating centanafadine, lisdexamfetamine, atomoxetine, and viloxazine were estimated using adjusted total utilities... While efficacy was highly valued by patients when making treatment decisions, safety attributes together had a greater relative importance than efficacy alone. Accordingly, ADHD treatments with favorable safety profiles may be preferred by patients. A better understanding of attributes of ADHD treatments valued by patients may help improve shared decision-making, enhance treatment satisfaction, and foster adherence."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder • Xerostomia

Baseline Characteristics of Pediatric and Adult Patients with ADHD Prescribed Viloxazine ER, Stimulants or Atomoxetine, in Open Claims Data (ISPOR 2024) - "OBJECTIVES: The novel non-stimulant Viloxazine ER (VLX; Qelbree®) received FDA approval for the treatment of pediatric (ages 6-17) ADHD in 2021 and adult ADHD in 2022... Across all age groups, patients filling prescriptions for novel VLX regimens tended to be younger and have more psychiatric diagnoses than those filling prescriptions for ATX regimens or stimulants. Further research is needed to determine whether the greater psychiatric complexity in patients receiving prescriptions for VLX regimens results from its recent market entry or prescription step-therapy rules; however, these demographic factors are important to consider in outcomes analyses."

Clinical • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • CNS Disorders • Depression • Genetic Disorders • Mood Disorders • Pediatrics • Psychiatry

Impact of Viloxazine Extended-Release Capsules (Qelbree®) on Select Cytochrome P450 Enzyme Activity and Evaluation of CYP2D6 Genetic Polymorphisms on Viloxazine Pharmacokinetics. (PubMed, Clin Drug Investig) - "Viloxazine ER is a strong CYP1A2 inhibitor and a weak CYP2D6 and CYP3A4 inhibitor. CYP2D6 polymorphisms did not meaningfully alter the viloxazine ER pharmacokinetic profile."

Journal • PK/PD data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry • CYP1A2

Evaluation of SPN-812 (Viloxazine Extended-release Capsule) in Preschool-age Children With ADHD (clinicaltrials.gov) - P4 | N=286 | Recruiting | Sponsor: Supernus Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting | N=160 ➔ 286

Enrollment change • Enrollment open • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Viloxazine ER Administered with Psychostimulants in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: Results of a Phase IV Safety Trial (AAPP 2024) - No abstract available

Clinical • P4 data • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry