Viloxazine
Selective norepinephrine reuptake inhibitor (NRI) with 5HT1A partial agonism, non-stimulant ADHD agent
Viloxazine
Qelbree
Viloxazine (brand name Qelbree) is an extended-release norepinephrine reuptake inhibitor FDA-approved in 2021 for ADHD in children 6 and older, and in 2022 for adults. Originally developed as an antidepressant in Europe in the 1970s (withdrawn for commercial reasons), it was repurposed for ADHD. Like atomoxetine, viloxazine is a non-stimulant alternative that is not a controlled substance. However, viloxazine has a more complex pharmacology than atomoxetine, beyond pure NET inhibition, it has 5HT1A partial agonism and 5HT2B/5HT7 antagonism, which may underlie faster onset (1-2 weeks vs atomoxetine's 4-6 weeks) and possibly different efficacy.
Useful when stimulants are contraindicated, undesirable, or insufficient. Can be combined with stimulants.
Selective NET inhibition (Ki ~155 nM). 5HT1A partial agonism, 5HT2B antagonism, 5HT2C inverse agonism, 5HT7 antagonism. Minimal DAT activity (key differentiator from stimulants).
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Effects
Somnolence (most common), decreased appetite, headache, insomnia, fatigue, nausea, irritability. Generally good tolerability. Boxed warning: suicidal ideation in pediatric patients (class warning for SNRIs/antidepressants used in pediatric ADHD).
Pharmacodynamics
Interactions
Fluoxetine via Category:Antidepressants exp n/a/5 outcome n/a (n=1) exp 1.0/5 outcome +33.0 (n=1)
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Summary
Classes
Selective norepinephrine reuptake inhibitor (NRI) with 5HT1A partial agonism, non-stimulant ADHD agent
Common uses
ADHD in children (6+), adolescents, and adults (FDA-approved 2021 for pediatric, 2022 for adult)
Pharmacy
Starting dose
Pediatric 6-11: 100 mg PO daily, titrate weekly to max 400 mg. Adolescent 12-17: 200 mg, max 400 mg. Adult: 200 mg, max 600 mg.
Preparations
100 mg, 150 mg, 200 mg extended-release capsules (can be sprinkled on food)
US FDA Max
400 mg/d (pediatric); 600 mg/d (adult)
Pharmacology
Routes
Oral
Onset
ADHD symptom improvement reported within 1-2 weeks (faster than atomoxetine which takes 4-6 weeks)
Duration
Daily dosing
Half-life
~7 hours
Bioavailability
Adequate oral bioavailability with extended-release formulation
Pregnancy
Limited data
Legal status
Rx, not a controlled substance (no DEA scheduling)
Purported mechanism
Selective NET inhibitor (no significant DAT activity, distinguishes from amphetamine/methylphenidate). Also: 5HT1A receptor partial agonism, 5HT2B and 5HT7 receptor antagonism. The serotonergic actions may underlie better tolerability and possibly different efficacy spectrum than atomoxetine.