If you've subscribed to the PDF of Cafer's Psychopharmacology, now's the time to re-download for bonus content. Qelbree is a strong CYP1A2 inHibitor with several listings and visualizations throughout the book.
Viloxazine (Qelbree)
❖ Norepinephrine reuptake inhibitor (NRI)
❖ Serotonin norepinephrine modulating agent (SNMA)
FDA-approved for:
❖ ADHD (ages 6–17)
Used off-label for:
❖ Depression
❖ Narcolepsy / cataplexy
❖ Excessive daytime sleepiness
❖ Alcohol use disorder
❖ Enuresis (bedwetting)
Viloxazine (Qelbree) is a “non-stimulant” ADHD treatment approved for children in 2021. It was available in Europe from 1976–2002 as an antidepressant until withdrawn from market for business reasons. It costs about $300 monthly.
Viloxazine is a norepinephrine reuptake inhibitor (NRI) according to the label, which makes no mention of serotonin. Unofficially viloxazine is considered a serotonin-norepinephrine modulating agent (SNMA). In addition to blocking norepinephrine reuptake, viloxazine acts as a 5-HT2B antagonist and 5-HT2C agonist. Animal studies suggest that these serotonergic effects can suppress hyperactive behavior. Considering that viloxazine is only a moderate strength inhibitor of norepinephrine reuptake, it is possible that its serotonergic effects may be more important than its noradrenergic effect.
Viloxazine is commonly compared to atomoxetine (Strattera), another NRI. Both medications are approved solely for ADHD but reside in our Modern Antidepressants chapter based on mechanism of action. Atomoxetine is a stronger NRI that does not act at 5-HT2B or 5-HT2C receptors.
Viloxazine is contraindicated with MAOIs due to potential hypertensive effects. The label, again, makes no mention of serotonin or any possibility of serotonin syndrome. Viloxazine certainly does not act as a serotonin reuptake inhibitor (unlike atomoxetine which does have weak SRI activity).
Viloxazine can suppress appetite, likely by two mechanisms. All NRIs are expected to decrease appetite. Activation of 5-HT2C receptors is the principal mechanism of the weight loss medication lorcaserin (Belviq) —”I’d like 2C my feet”. However, only 7% of children taking viloxazine reported loss of appetite.
Viloxazine can cause increase heart rate and diastolic blood pressure, observed in about 20% of patients. Other side effects may include somnolence (16%), fatigue (6%), nausea (5%), vomiting (4%), insomnia (4%), and irritability (3%).
The label has the standard boxed warning of suicidal thoughts and behaviors. Noradrenergic drugs such as viloxazine could theoretically induce a manic episode in patients with bipolar disorder.
Viloxazine does not cause anticholinergic effects or QT prolongation. Unlike with atomoxetine, there is no known risk of hepatotoxicity with viloxazine.
Prior to release of viloxazine, fluvoxamine (Luvox) was the only strong 1A2 inHibitor that we had to contend with. Viloxazine is a strong 1A2 inHibitor but not a “fluffer” inHibitor like fluvoxamine because viloxazine’s weak inhibitory effect on other CYP enzymes (2D6, 3A4) is not expected to be clinically significant.
Viloxazine is eliminated renally. Half-life is 7 hours with Qelbree, which is an extended-release capsule. If it were immediate-release, half-life would only be 2–3 hours. Serum levels of viloxazine are 40–50% higher in children age 6–11 compared to age 12–17.
Designing the mascot was challenging, given similarities in name with the antidepressant vilazodone (Viibryd) or the antipsychotic loxapine. The mascot is not ideal because viloxazine is not a nasal spray, but the mnemonic was field-tested as effective for recollection of the generic name if “lock” is inserted as the second syllable of “Vi-zine”. Visine is popular brand of eye drops containing a vasoconstrictor to treat bloodshot eyes—”God’s gift to stoners”, although this has nothing to do with Qelbree.
Dynamic interactions:
❖ Hypertensive effects
❖ Serotonergic
❖ Appetite suppression
Kinetic interactions:
❖ 1A2 inHibitor (strong)
➤ Contraindicated with sensitive 1A2 substrates:
– duloxetine (Cymbalta)
– ramelteon (Rozerem)
– tasimelteon (Hetlioz)
– tizanidine (Zanaflex)
– theophylline
➤ Adjust dose of clozapine (1A2 substrate) if coadministered with viloxazine
Dosing: Start 100 mg QD for ages 6–11 and 200 mg QD for ages 12–17. May titrate in increments of 100 mg weekly depending on response and tolerability. FDA maximum is 400 mg QD for all ages. May be taken with or without food. May open capsules and sprinkle on applesauce. Dose at half strength if severe renal impairment (eGFR < 30).