Is it wise to explore viloxazine (a norepinephrine reuptake inhibitor) now that I've discontinued Strattera (atomoxetine) for over a year?

Viloxazine After Strattera Discontinuation

Yes, it is reasonable to explore viloxazine (Qelbree) now that you have discontinued Strattera (atomoxetine) for over a year, as viloxazine represents a distinct nonstimulant option with a different pharmacological profile and potentially superior tolerability compared to atomoxetine. 1

Key Differences Between Viloxazine and Atomoxetine

While both medications function as norepinephrine reuptake inhibitors, viloxazine has important mechanistic distinctions that make it a viable alternative:

• Viloxazine is classified as a "serotonin norepinephrine modulating agent" with moderate activity at serotonin 5-HT2C receptors (partial agonist activity), representing a dual mechanism that differs from atomoxetine's pure norepinephrine reuptake inhibition. 2, 3

• Direct comparison studies demonstrate that patients switching from atomoxetine to viloxazine experience significantly greater improvement in ADHD symptoms, with 86% reporting positive response by 2 weeks on viloxazine versus only 14% on atomoxetine. 1

• Viloxazine shows superior tolerability, with only 4% discontinuation rate due to side effects compared to 36% discontinuation rate with atomoxetine (primarily due to GI upset, irritability, and fatigue). 1

Clinical Considerations for Starting Viloxazine

Timing After Atomoxetine Discontinuation

• Your one-year gap since discontinuing Strattera is more than adequate, as atomoxetine has a half-life of approximately 5 hours (21 hours in poor CYP2D6 metabolizers), meaning complete elimination occurs within days to weeks at most. 3

• No washout period is required when switching between these medications in clinical practice, though studies have used a 5-day washout for research purposes. 1

Expected Response Timeline

• Therapeutic effects may not be observed until 2-4 weeks after initiation, though some patients show benefits as early as week 2. 4

• This represents a faster onset compared to atomoxetine, where optimal response typically requires 4-6 weeks or longer. 1

Dosing Strategy

• Start viloxazine ER at 200 mg once daily in the morning. 5

• Titrate by 200 mg increments at weekly intervals based on response and tolerability, up to a maximum of 600 mg/day. 5

• Take with or without food, though high-fat meals delay absorption by approximately 2 hours without significantly affecting overall exposure. 3

Safety Profile and Monitoring

Common Adverse Effects to Anticipate

• Gastrointestinal symptoms (nausea, vomiting, abdominal discomfort, diarrhea) are the most commonly reported side effects but occur less frequently than with atomoxetine. 5

• Other common effects include somnolence, decreased appetite, headache, and fatigue, which are generally mild and transient. 5, 6

• Cardiovascular monitoring for increased blood pressure and pulse is recommended, though clinically significant changes are uncommon. 5

Serious Risks Requiring Awareness

• Black box warning for suicidal thinking and behavior exists (through age 24 years), as viloxazine was historically used as an antidepressant, though this risk appears lower than with atomoxetine in clinical experience. 5

• Monitor for behavioral activation, agitation, hypomania, or mania, particularly in patients with comorbid mood disorders. 5

• Serotonin syndrome risk exists when combining with other serotonergic agents (SSRIs, SNRIs, MAOIs, tramadol, etc.), requiring caution with concomitant medications. 2, 5

• Viloxazine does not prolong QT interval at therapeutic doses, unlike some concerns with atomoxetine. 3

Advantages Over Your Previous Atomoxetine Trial

Efficacy Considerations

• In pediatric patients, viloxazine produced mean ADHD-RS-5 scores of 13.9 compared to 33.1 with atomoxetine (lower scores indicate better control), representing a clinically meaningful difference. 1

• In adults, viloxazine produced mean AISRS scores of 11.9 compared to 28.8 with atomoxetine, with improvements in both inattention and hyperactivity/impulsivity domains. 1

• 96% of patients in comparative studies preferred viloxazine over atomoxetine. 1

Tolerability Advantages

• Viloxazine demonstrates minimal dopamine elevation in the nucleus accumbens, resulting in negligible abuse potential and no evidence of drug dependence or withdrawal symptoms. 7, 8

• The extended-release formulation allows once-daily dosing with steady-state achieved after 2 days, providing consistent symptom control throughout the day. 4, 3

Clinical Pitfalls to Avoid

• Do not assume viloxazine will be ineffective simply because atomoxetine failed—the dual serotonergic-noradrenergic mechanism provides a distinct therapeutic approach. 2, 1

• Avoid combining viloxazine with other serotonergic medications without careful monitoring for serotonin syndrome, particularly in the first 24-48 hours after starting or dose adjustments. 2, 5

• Do not discontinue abruptly if viloxazine proves effective, as gradual tapering is recommended despite the lack of formal discontinuation syndrome data. 5

• Ensure adequate trial duration (minimum 4 weeks at therapeutic dose) before concluding lack of efficacy, as response may be delayed. 4