Quelbree (Viloxazine): A Non-Stimulant Medication for ADHD
Quelbree (viloxazine extended-release) is a selective norepinephrine reuptake inhibitor FDA-approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and children 6 years of age and older. 1, 2
Mechanism of Action and Classification
- Viloxazine functions primarily by inhibiting the reuptake of norepinephrine, though its exact mechanism of action in treating ADHD is not fully understood 1, 2
- It is classified as a "serotonin norepinephrine modulating agent" with activity in both noradrenergic and serotonergic pathways 3
- Unlike stimulant medications, viloxazine has a decreased potential for substance abuse, drug dependence, and withdrawal symptoms 2
Formulation and Dosing
- Available as extended-release capsules in strengths of 100 mg, 150 mg, and 200 mg 1
- For adults with ADHD, treatment typically starts at 200 mg once daily 4
- Can be titrated by 200 mg increments at weekly intervals based on response and tolerability 4
- Maximum recommended daily dose is 600 mg/day 4
- In clinical trials, most adult patients (73%) required doses ≥400 mg/day for optimal symptom control 5
- For children aged 6-11 years, treatment typically starts at 100 mg once daily, while adolescents aged 12-17 years start at 200 mg once daily 6
Clinical Efficacy
- Phase III clinical trials have demonstrated significant efficacy in improving ADHD symptoms compared to placebo in both pediatric and adult populations 6, 7
- In adults, viloxazine showed significant improvements in the ADHD Investigator Symptom Rating Scale (AISRS) total score as early as 2 weeks after treatment initiation 7
- Long-term studies show sustained improvement in ADHD symptoms with continued use 5, 6
- Improvements were noted in both inattention and hyperactivity/impulsivity domains 7
Administration
- Capsules should be swallowed whole or contents can be sprinkled over a teaspoonful of applesauce or pudding 1
- When mixed with pudding, the mixture should be consumed within 15 minutes; when mixed with applesauce, within 2 hours 1
- Do not cut, chew, or crush the capsules 1
- Can be taken with or without food 1
Common Side Effects
- Most common adverse events (occurring in ≥5% of patients) include: 1, 5, 6
- Insomnia (14.8%)
- Fatigue (10-11.6%)
- Nausea (10.1-13.8%)
- Headache (8.9-10.7%)
- Decreased appetite (6.0-10.1%)
- Somnolence (9.5%)
- Dry mouth (9.0%)
Important Safety Considerations
- Boxed warning: Increased risk of suicidal thoughts or actions, particularly in children and adolescents 1
- May increase blood pressure and heart rate 1
- Can cause somnolence and fatigue that may impair ability to drive or operate machinery 1
- May affect weight; monitoring is recommended 1
- Not recommended during pregnancy without careful risk-benefit assessment 4, 1
- Limited data available regarding use during breastfeeding; caution is advised 4, 1
- Contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or who have discontinued MAOIs within the last 14 days 1
- Also contraindicated with alosetron, duloxetine, ramelteon, tasimelteon, tizanidine, or theophylline 1
Historical Context
- Viloxazine was originally developed in the 1970s and used as an antidepressant in Europe for approximately 30 years before being withdrawn from European markets in 2002 3
- The extended-release formulation (Quelbree) was approved by the FDA in April 2021 for pediatric ADHD and later expanded to include adults 2, 8
Place in Therapy
- Viloxazine provides a non-stimulant alternative for ADHD treatment 2
- Particularly useful for patients who:
Dosage Adjustment in Special Populations
- Dosage reduction is recommended in patients with severe renal impairment (eGFR <30 mL/min/1.73m²) 1
- No dosage adjustment needed in patients with mild to moderate renal impairment 1
Viloxazine represents an important addition to the ADHD treatment armamentarium as a non-stimulant option with demonstrated efficacy and a generally favorable safety profile.