What is the difference between Strattera (atomoxetine) and Qelbree (viloxazine) in the treatment of Attention Deficit Hyperactivity Disorder (ADHD)?

Strattera vs. Qelbree: Key Differences for ADHD Treatment

Both Strattera (atomoxetine) and Qelbree (viloxazine ER) are nonstimulant medications for ADHD that work primarily through norepinephrine modulation, but Strattera has a substantially larger evidence base spanning two decades while Qelbree is the first novel nonstimulant approved in over 20 years with limited adult efficacy data. 1, 2

Mechanism of Action

Strattera (Atomoxetine):

• Selective norepinephrine reuptake inhibitor (NRI) with high affinity and selectivity for norepinephrine transporters 3
• Preferentially binds to areas with high distribution of noradrenergic neurons, particularly the fronto-cortical subsystem 3
• Effect size approximately 0.7 compared to stimulants at 1.0 1

Qelbree (Viloxazine ER):

• Serotonin-norepinephrine modulating agent (SNMA) - functions as a norepinephrine reuptake inhibitor with additional serotonergic pathway activity 2, 4
• Originally used as an antidepressant outside the U.S. for decades 5
• Elevates dopamine levels in the nucleus accumbens considerably less than traditional stimulants 2

Dosing and Administration

Strattera:

• Available in capsules: 10,18,25,40,60,80, or 100 mg, plus oral solution (4 mg/ml) 1
• Weight-based titration with maximum dose of 1.4 mg/kg/day or 100 mg/day, whichever is lower 1
• Can be administered once daily or split into two evenly divided doses 3

Qelbree:

• Starting dose: 200 mg once daily 1
• Titrate by 200 mg increments at weekly intervals based on response and tolerability 1
• Maximum daily dose: 600 mg/day 1
• Once-daily extended-release formulation addresses the multiple daily dosing limitation of the original viloxazine 5

Metabolism and Drug Interactions

Strattera:

• Primarily metabolized through CYP2D6 pathway 1
• Critical consideration: Approximately 7% of the population are poor CYP2D6 metabolizers with significantly higher plasma levels, longer half-lives, and increased adverse effects 1, 3
• Selective serotonin reuptake inhibitors (SSRIs) can elevate serum atomoxetine levels 1
• CYP2D6 inhibitors like paroxetine cause pharmacokinetic changes similar to poor metabolizers 3

Qelbree:

• Metabolized by CYP enzymes, particularly CYP1A2 4
• Special consideration needed when co-administering with antiepileptic drugs, as they inhibit CYP1A2 4
• Requires close monitoring in individuals with liver or cardiovascular disease 4

Evidence Base and Efficacy

Strattera:

• Extensive evidence base with approval in multiple countries for children, adolescents, and adults 1
• Significantly more effective than placebo and standard current therapy 3
• Does not differ significantly from or is noninferior to immediate-release methylphenidate 3
• However, significantly less effective than extended-release methylphenidate (OROS) and extended-release mixed amphetamine salts 3
• Demonstrated long-term efficacy with single morning dose effective into evening, no symptom rebound upon discontinuation 3

Qelbree:

• Limited data available on efficacy, safety, and tolerability for ADHD treatment in adults 1
• Effect size appears less than observed for stimulants, though direct comparisons have not been made 5
• First nonstimulant approved for ADHD in more than a decade 5
• Approved in the U.S. for children and adolescents aged 6 and older; not currently available in Canada 1

Safety Profile and Adverse Effects

Strattera:

• FDA black box warning for suicidal ideation in children and adolescents - requires close monitoring especially during first few months of treatment or dose changes 1, 6
• Most common adverse effects: nausea, vomiting, fatigue, decreased appetite, abdominal pain, somnolence 1
• Additional warnings for cardiovascular disease, psychotic/manic symptoms, aggressive behavior, effects on growth, and priapism 1
• Rare but serious: hepatitis (three cases in postmarketing data deemed probably related to atomoxetine) 3
• Initial loss in expected height and weight eventually returns to normal long-term 3
• Negligible risk of abuse or misuse; not a controlled substance 3

Qelbree:

• No published studies on safety in pregnancy or breastfeeding 1
• Requires close monitoring in patients with personal or family history of bipolar disorder 4
• Decreased chance of substance abuse, drug dependence, and withdrawal symptoms compared to stimulants 2
• Relatively safe profile based on decades of use as antidepressant outside the U.S. 4

Clinical Decision-Making Algorithm

Choose Strattera when:

• Patient has complex psychiatric comorbidities (schizoaffective disorder, psychosis risk) - lower risk of exacerbating psychotic symptoms 6
• Extensive evidence base needed for confidence in treatment decisions 1, 3
• Patient is an adult requiring well-established efficacy data 1
• Co-morbid anxiety or tics present 3
• Risk of substance abuse is a concern 3
• Caveat: Check CYP2D6 metabolizer status if available; poor metabolizers require dose adjustment and closer monitoring 1, 3

Choose Qelbree when:

• Strattera has failed or was not tolerated 2, 5
• Patient cannot tolerate stimulants or has contraindications 2
• Serotonergic modulation may provide additional benefit (co-morbid depression, anxiety) 2, 4
• Once-daily dosing adherence is critical 5
• Caveat: Alternative agents are preferred in adults due to limited efficacy data 1

Important Clinical Pitfalls

For Strattera:

• Failure to monitor for suicidal ideation in pediatric patients, particularly in first months of treatment 1, 6
• Not accounting for drug interactions with SSRIs or CYP2D6 inhibitors 1, 3
• Missing poor CYP2D6 metabolizers who require lower doses 1, 3

For Qelbree:

• Using as first-line in adults without discussing limited efficacy data 1
• Missing drug interactions with antiepileptics that inhibit CYP1A2 4
• Inadequate monitoring in patients with liver or cardiovascular disease 4
• Prescribing without risk-benefit discussion acknowledging lack of pregnancy/breastfeeding safety data 1

Both medications should be tapered rather than abruptly discontinued, and neither should be used as first-line before considering stimulants, which have superior efficacy (effect size ~1.0 vs ~0.7 for nonstimulants). 1, 3, 5