What is the role of Qelbree (viloxazine) in treating attention deficit hyperactivity disorder (ADHD) in children and adults?

Qelbree (Viloxazine Extended-Release) for ADHD Treatment

Qelbree is an FDA-approved, non-stimulant selective norepinephrine reuptake inhibitor indicated for treating ADHD in both children (≥6 years) and adults, offering a valuable alternative when stimulants are contraindicated, poorly tolerated, or ineffective. 1

FDA-Approved Indications and Patient Population

• Qelbree is approved for ADHD treatment in adults and pediatric patients 6 years and older 1
• The medication represents the first novel non-stimulant ADHD treatment approved for adults in the past two decades 2
• It functions as a selective norepinephrine reuptake inhibitor with additional modulatory effects on the serotonergic system 3, 2

Dosing Algorithms by Age Group

Pediatric Patients (6-11 years):

• Start at 100 mg once daily in the morning 1
• Titrate in 100 mg weekly increments based on response and tolerability 1
• Maximum dose: 400 mg/day 1
• Median maintenance dose in long-term studies: 300 mg/day 4

Adolescents (12-17 years):

• Start at 200 mg once daily in the morning 1
• After 1 week, may increase by 200 mg to maximum 400 mg/day 1
• Median maintenance dose in long-term studies: 400 mg/day 4

Adults:

• Start at 200 mg once daily in the morning 1
• Titrate in 200 mg weekly increments 1
• Maximum dose: 600 mg/day 1
• In long-term studies, 73% of adults used doses ≥400 mg/day, with 36% requiring 600 mg/day 5

Timeline for Therapeutic Response

• Therapeutic effects may not be observed until 2-4 weeks after initiation 6
• However, significant improvements in ADHD symptoms were demonstrated as early as week 2 in adult trials 7
• Continued improvement occurs over subsequent months with sustained long-term benefit 5, 4

Efficacy Evidence

Adult Population:

• In the pivotal Phase III trial, viloxazine ER demonstrated statistically significant improvement in ADHD symptoms (AISRS total score) compared to placebo at week 6 (p=0.0040) 7
• Significant improvements were also seen in inattention, hyperactivity/impulsivity, executive function (BRIEF-A), and overall clinical severity (CGI-S, p=0.0023) 7
• Long-term open-label extension showed sustained efficacy with mean AISRS improvement of -18.2 points maintained over 265 days of treatment 5

Pediatric Population:

• Long-term safety trial (N=1100) demonstrated sustained ADHD symptom improvement with mean ADHD-RS changes of -24.3 at Month 3, -26.1 at Month 12, and -22.4 at last visit 4
• The medication showed relatively rapid onset with sustained symptom improvement and clinical benefit in ADHD-associated functional and social impairments 3

Critical Safety Warnings and Monitoring

Black Box Warning:

• Higher rates of suicidal thoughts and behavior were reported in ADHD patients treated with Qelbree versus placebo 1
• Closely monitor all patients for clinical worsening and emergence of suicidal thoughts and behaviors 1
• Screen patients for personal or family history of suicide, bipolar disorder, and depression before initiating treatment 1

Cardiovascular Monitoring:

• Assess heart rate and blood pressure prior to initiation, following dose increases, and periodically during therapy 1

Common Adverse Events:

Adults (≥5% incidence): 7, 5

• Insomnia (13.8-14.8%)
• Fatigue (10.1-11.6%)
• Nausea (10.1-13.8%)
• Decreased appetite (10.1%)
• Dry mouth (9.0%)
• Headache (9.0-10.7%)

Pediatric patients (≥5% incidence): 4

• Nasopharyngitis (9.7%)
• Somnolence (9.5%)
• Headache (8.9%)
• Decreased appetite (6.0%)
• Fatigue (5.7%)

Discontinuation Rates:

• Adults: 9.0% discontinued due to adverse events in acute trials, 17.6% in long-term extension 7, 5
• Pediatrics: 8.2% discontinued due to adverse events in long-term extension 4
• Most adverse events were mild to moderate in severity 5, 4

Special Population Considerations

Pregnancy:

• Viloxazine should be discontinued when pregnancy is recognized due to limited safety data 6
• Alternative agents are preferred during pregnancy 6

Renal Impairment:

• Severe renal impairment (eGFR <30 mL/min/1.73m²): Start at 100 mg once daily, titrate in 50-100 mg weekly increments to maximum 200 mg/day 1
• Mild to moderate renal impairment: No dosage adjustment required 1

Limited Adult Data Caveat:

• While FDA-approved for adults, viloxazine has more extensive efficacy data in pediatric populations compared to adults 6

Administration Considerations

• Administer once daily in the morning for optimal symptom control throughout the day 8, 6, 1
• May be taken with or without food 1
• Capsules should be swallowed whole, or opened and sprinkled over pudding/applesauce (consume within 15 minutes for pudding, 2 hours for applesauce) 1
• Do not cut, crush, or chew capsules 1

Role in Treatment Algorithm

When to Consider Qelbree:

First-line non-stimulant option when: 9, 3, 2

• Stimulants are contraindicated (e.g., cardiovascular disease, substance use disorder history)
• Patient preference for non-stimulant medication
• Comorbid anxiety where stimulants may worsen symptoms
• Concerns about stimulant abuse potential

Augmentation strategy:

• Consider adding a stimulant (methylphenidate or amphetamine) for residual ADHD symptoms in patients already on Qelbree, with careful monitoring for irritability, insomnia, feeding difficulty, and cardiovascular effects 8
• Stimulants show larger effect sizes than non-stimulants for ADHD core symptoms 8

Context Within ADHD Treatment Landscape:

• Stimulants (methylphenidate and amphetamine) remain first-line pharmacotherapy for ADHD with the strongest evidence base 9
• Qelbree provides an important non-stimulant alternative with a different mechanism of action (norepinephrine reuptake inhibition) 1, 3
• The medication addresses a clinical need for effective non-stimulant options, particularly given that current treatments may be suboptimal with low response rates and tolerability issues 3

Long-Term Treatment Considerations

• Periodically reevaluate the long-term use of Qelbree and adjust dosage as needed, as pharmacological treatment of ADHD may be needed for extended periods 1
• Long-term safety data up to 72 months in pediatrics and extended follow-up in adults support sustained use 5, 4
• No new long-term safety concerns emerged in extension studies 5, 4