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Qelbree (viloxazine ER)

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Newer (FDA 2021 pediatric, 2022 adult) non-stimulant ADHD drug from Supernus — repurposed European antidepressant (1970s–2000s as Vivalan)… | Pharmaceutical · Oral

Aliases (8)
Qelbree · viloxazine · viloxazine extended-release · viloxazine ER · SPN-812 · Vivalan · Emovit · Vicilan
TYPICAL DOSE
100 mg
ROUTE
Oral (tablet)
CYCLE
No cycling needed or recommended. Daily steady-…
STORAGE
Room temp; original container
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▸Brand options5 known
QelbreeSPN-812VivalanEmovitVicilan

StatusRx, unscheduled (US — not controlled)

▸ Overview TL;DR

Newer (FDA 2021 pediatric, 2022 adult) non-stimulant ADHD drug from Supernus — repurposed European antidepressant (1970s–2000s as Vivalan) reformulated as extended-release. Multimodal mechanism: NRI + 5-HT2C partial agonist + 5-HT2B antagonist. A-tier ADHD evidence in target populations, faster onset than atomoxetine (~1–2 weeks vs 4), but no cognitive enhancement evidence in healthy adults and a black-box warning for suicidal ideation. Skip for Dylan — he has no ADHD diagnosis, modafinil/bromantane/Adamax/Semax cover the cognitive-output use case better, and the side-effect-to-benefit ratio is wrong for non-clinical brain enhancement.

▸ Mechanism of action

Viloxazine has the most pharmacologically interesting profile of the non-stim ADHD drugs — it's not just an NRI like atomoxetine. The full picture:

Primary action — norepinephrine reuptake inhibition:

  • Blocks NET (norepinephrine transporter), increasing synaptic NE in prefrontal cortex and locus coeruleus efferents
  • Notably weaker NRI affinity than atomoxetine — meaning the NRI effect alone is not the whole story; the 5-HT receptor activity matters

Secondary action — multimodal serotonergic modulation:

  • 5-HT2C partial agonist: Activates inhibitory interneurons that normally suppress mesocortical dopamine tone; partial agonism modulates this rather than over-activating it. Net result: increased prefrontal dopamine via disinhibition, without DAT blockade.
  • 5-HT2B antagonist: Blocks pro-fibrotic, pro-anxiety serotonergic signaling. (5-HT2B agonism is the cardiac-fibrosis mechanism behind fenfluramine and pergolide withdrawals; antagonism is protective on this axis.)
  • 5-HT7 antagonist: Modulates circadian and mood-related serotonergic tone; mechanism shared with several atypical antidepressants and considered pro-cognitive in some preclinical models.

Net biochemistry: Increases prefrontal cortex NE, 5-HT, AND DA — without binding DAT directly. This is why Supernus markets it as having "amphetamine-like CNS stimulant effects without evidence of dependence." The dopamine elevation is real but indirect, ceiling-limited, and doesn't drive the same reinforcement loops as direct DA reuptake inhibition (cocaine, methylphenidate) or DA release (amphetamine).

The "old European antidepressant" backstory: Viloxazine was approved in Europe in the 1970s as Vivalan (also Emovit, Vicilan), used for depression for ~30 years. It was withdrawn in the early 2000s for commercial reasons, not safety — newer SSRIs/SNRIs displaced it. Supernus acquired the molecule, developed an extended-release formulation (SPN-812), repositioned for ADHD, ran the trials, and brought it through FDA approval. Classic pharma repurposing — the safety database was already large from decades of European antidepressant use.

Half-life: ~7 hours (parent), but the ER formulation supports once-daily dosing with extended absorption.

▸ Pharmacokinetics Approximate
t½: ~7 hours (parent)
100% 50% 0% 0 9h 18h 26h 35h t½ Peak

Approximate decay curve drawn from the half-life mention(s) in the source notes. Real PK data not yet ingested per compound.

▸Research indications1 use cases

Notably weaker NRI affinity than atomoxetine

Most effective

meaning the NRI effect alone is not the whole story; the 5-HT receptor activity matters

▸Research protocols1 protocols
GoalDoseFrequencySoloCycle
Once-daily AM dosing————

Auto-extracted from dosing notes. For full context including caveats and Dylan-specific protocols, see the Dosing protocols section.

▸Quality indicators4 checks
✓
FDA-approved manufacturer
NDC code on the bottle matches FDA registration. Generic OK; backyard not OK.
✓
Brand vs generic listed
Pharmacy fills should disclose substitution. AB-rated generics are bioequivalent.
✓
Tamper-evident packaging
Pharmacy seal intact, lot number + expiry visible on the bottle and the box.
!
Schedule labeling correct
C-II / C-IV warnings on label match the medication; report any mismatch to the pharmacist.
▸ What to expect Generic
  1. 1
    Day 1
    PK-driven acute peak per administration. Verify dose tolerated.
  2. 2
    Week 1
    Steady-state reached for most daily-dosed pharma.
  3. 3
    Week 2-4
    Therapeutic effect established; titration window if needed.
  4. 4
    Long-term
    Periodic monitoring per drug class (labs, BP, ECG as applicable).
▸ Side effects + safety

  • Common (>10% in pediatric trials):

    • Somnolence — 16% (vs 4% placebo) — the dominant complaint; can be activity-limiting
    • Decreased appetite (~7–8%)
    • Headache
    • Fatigue
    • Nausea
    • Vomiting
    • Insomnia (paradoxically — somnolence in some, insomnia in others)
    • Irritability

  • Less common (1–10%):

    • Increased blood pressure + heart rate (modest, but real — class effect of NRIs)
    • Constipation
    • Decreased libido
    • Diaphoresis
    • Dry mouth
    • Lethargy / sluggish cognition
    • Nasopharyngitis (likely incidental, but listed at ~10% in long-term extension)

  • Rare-serious (<1% but worth knowing):

    • Suicidal ideation/behavior — FDA BLACK BOX WARNING (all ages): 0.9% incidence in pediatric trials (n=1019) vs 0.4% placebo; 1.6% in adult trials (n=189) vs 0% placebo. The signal is small in absolute terms but statistically real. Most concerning: this is one of the few ADHD medications with a black-box specifically for suicidal ideation, and the warning applies to all ages — not just <25yo as with general antidepressants.
    • Mania/hypomania activation in undiagnosed bipolar — class-typical for NE-pushing agents
    • Hypertensive episodes — monitor BP/HR in cardiovascular-risk patients
    • Hepatic enzyme elevation — case-level reports; LiverTox classifies as low-grade hepatotoxicity risk
    • Serotonin syndrome if combined with other serotonergic agents at high doses (theoretical but plausible given multimodal 5-HT activity)

  • Specific watch periods:

    • First 4 weeks: Suicidal-ideation watch (highest risk during initiation)
    • First 8 weeks: Mood activation (mania, agitation, severe insomnia)
    • Ongoing: BP/HR monitoring; hepatic check at 6–8 weeks if any abdominal symptoms
▸Interactions8 compounds
  • modafinil:Synergistic
    Mechanistically complementary — modafinil pushes orexin/histamine/glutamate wake systems with mild DA effect; viloxazine adds NE reuptake inhibition + indire…
  • caffeine:Synergistic
    Likely safe co-administration. No documented interaction. Caffeine's adenosine-mediated wake-pushing is mechanistically distinct from viloxazine's NE/5-HT.
  • L-tyrosine, L-theanine, magnesium, NAC, citicoline, fish oil, PS (V4 core):Synergistic
    Stack-safe. No PK/PD conflicts with viloxazine.
  • MAOIs (selegiline at non-selective doses ≥10 mg, phenelzine, tranylcypromine):Avoid
    Risk of hypertensive crisis from combined NE elevation + multimodal 5-HT. 14-day washout in either direction is the standard. Low-dose MAO-B-selective selegi…
  • Other strong NRIs (atomoxetine, reboxetine):Avoid
    Redundant + additive cardiovascular load.
  • Other strong serotonergics (high-dose SSRIs, SNRIs, MDMA, certain triptans, tramadol):Avoid
    Theoretical serotonin syndrome risk via the 5-HT receptor multimodal activity — clinically the risk seems low but the mechanism warrants caution.
  • CYP1A2 substrates (theophylline, clozapine, tizanidine, ramelteon):Avoid
    Viloxazine is a strong CYP1A2 inhibitor — substantially increases exposure of these substrates. Multiple drug-interaction warnings in the FDA label.
  • CYP2D6 substratesAvoid
    (some opioids, beta-blockers, antiarrhythmics): Viloxazine is a weak CYP2D6 inhibitor — modest but real interaction surface.
▸References31 sources

Viloxazine - Wikipedia

broad overview, European antidepressant history, mechanism summary

en.wikipedia.orgView →

Viloxazine: Pediatric First Approval - PubMed (Markham 2021)

2021

primary pediatric approval review

pubmed.ncbi.nlm.nih.govView →

Viloxazine: Pediatric First Approval - PMC (Markham 2021)

2021

full text version of approval review

pmc.ncbi.nlm.nih.govView →

Supernus Announces FDA Approval of Qelbree™ (SPN-812) for ADHD

2021

primary corporate approval announcement (April 2021)

ir.supernus.comView →

Supernus Announces Label Update for Qelbree® (Pharmacodynamic Data + Breastfeeding)

2024

2024 label update with multimodal pharmacology details

ir.supernus.comView →
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