What is the use and dosage of Viloxazine (a selective norepinephrine reuptake inhibitor) for treating depression and Attention Deficit Hyperactivity Disorder (ADHD)?

Viloxazine Use and Dosage for ADHD and Depression

Viloxazine (Qelbree) is FDA-approved as a selective norepinephrine reuptake inhibitor for the treatment of ADHD in adults and pediatric patients 6 years and older, but is not currently approved for depression despite its historical use as an antidepressant. 1

Mechanism of Action

• Viloxazine functions primarily as a selective norepinephrine reuptake inhibitor, though it also increases serotonin levels in the prefrontal cortex and exhibits moderate activity at noradrenergic and dopaminergic systems 2
• It is classified as a serotonin norepinephrine modulating agent with serotonin modulating activity considered "an important (if not the predominant) component of its mechanism of action" 2

Historical Context

• Originally developed in the 1970s and used as an antidepressant outside the United States until withdrawn from markets in 2002 2
• Recently repurposed and approved by the FDA in 2021 specifically for ADHD treatment, not for depression 1, 3

Dosage for ADHD

Pediatric Patients (6-11 years):

• Starting dose: 100 mg once daily 1
• Titration: May increase in 100 mg weekly increments 1
• Maximum recommended dose: 400 mg once daily 1

Adolescents (12-17 years):

• Starting dose: 200 mg once daily 1
• Titration: May increase after 1 week by 200 mg 1
• Maximum recommended dose: 400 mg once daily 1

Adults:

• Starting dose: 200 mg once daily 1
• Titration: May increase in 200 mg weekly increments 1
• Maximum recommended dose: 600 mg once daily 1

Administration

• Recommended to be taken once daily in the morning for optimal symptom control 4
• Capsules may be swallowed whole or opened and contents sprinkled onto applesauce or pudding 1
• Morning administration is preferred for non-stimulant ADHD medications like viloxazine 4

Special Populations

Severe Renal Impairment:

• Starting dose: 100 mg once daily 1
• Titration: Increase in weekly increments of 50-100 mg 1
• Maximum recommended dose: 200 mg once daily 1

Pregnancy and Breastfeeding:

• No published information on viloxazine's safety during pregnancy or breastfeeding 2
• Alternative agents are preferable in these populations 2, 4

Efficacy and Clinical Considerations

• Viloxazine ER has demonstrated favorable efficacy and tolerability in clinical trials for ADHD 2
• Effect size is less than observed for stimulants, though direct comparisons have not been conducted 5
• Treatment effects are not usually observed until 2-4 weeks after initiation 4
• May be beneficial for patients with comorbid depression 6

Important Warnings and Adverse Effects

• Boxed warning for suicidal thoughts and behaviors, requiring close monitoring 1
• Most common adverse reactions in pediatric patients (≥5% and at least twice placebo rate): somnolence, decreased appetite, fatigue, nausea, vomiting, insomnia, and irritability 1
• Most common adverse reactions in adults: insomnia, headache, somnolence, fatigue, nausea, decreased appetite, dry mouth, and constipation 1
• Can cause blood pressure and heart rate increases; assessment recommended prior to treatment, following dosage increases, and periodically during therapy 1

Use for Depression

• Despite its historical use as an antidepressant, viloxazine is not currently FDA-approved for depression treatment 2
• No current dosing guidelines exist for depression as its use has been repurposed specifically for ADHD 3

Combination Therapy

• Can be used as add-on therapy with psychostimulants when monotherapy provides inadequate response 7
• Combination therapy has shown acceptable safety and tolerability with improvements in ADHD behaviors 7