How should I transition a patient from atomoxetine (Strattera) to viloxazine (Qelbree)?

Switching from Strattera (Atomoxetine) to Qelbree (Viloxazine ER)

You can switch directly from atomoxetine to viloxazine ER after a brief 5-day washout period, then titrate viloxazine ER according to FDA guidelines based on age and weight.

Washout Period

• A 5-day washout period between discontinuing atomoxetine and initiating viloxazine ER is sufficient based on clinical practice data showing safe and effective transitions with this timeline 1
• Atomoxetine has a half-life that allows for relatively rapid clearance, making extended washout periods unnecessary 2

Discontinuation of Atomoxetine

• Taper atomoxetine gradually over 3-5 days rather than stopping abruptly to minimize potential discontinuation symptoms, though atomoxetine discontinuation is generally well-tolerated with low incidence of discontinuation-emergent adverse events 2
• Monitor for any return of ADHD symptoms during the washout period 1

Initiation of Viloxazine ER

Pediatric Patients (6-11 years)

• Start viloxazine ER at 100 mg once daily in the morning 3
• Titrate upward based on response and tolerability over a 12-week dose-optimization period 3
• Maximum dose is 400 mg/day for children 3
• The median modal dose in clinical trials was 300 mg/day for children 3

Adolescent Patients (12-17 years)

• Start viloxazine ER at 200 mg once daily in the morning 3
• Titrate as needed over a 12-week dose-optimization period 3
• Maximum dose is 600 mg/day for adolescents 3
• The median modal dose in clinical trials was 400 mg/day for adolescents 3

Adult Patients

• Start viloxazine ER at 200 mg once daily based on FDA approval for adult ADHD 4
• Titrate weekly by 200 mg increments based on response and tolerability 5
• Maximum dose is 600 mg/day for adults 5

Expected Timeline for Response

• 86% of patients report positive response to viloxazine ER by 2 weeks, which is significantly faster than atomoxetine where only 14% responded by 2 weeks 1
• This represents a major advantage over atomoxetine, which requires 4-6 weeks for full therapeutic effect 2, 6
• Viloxazine ER demonstrates onset of action in approximately 1-2 weeks compared to atomoxetine's 4-week timeline 6

Monitoring During the Switch

Baseline Assessment (Before Starting Viloxazine ER)

• Measure blood pressure and pulse 5
• Document current ADHD symptom severity using standardized rating scales (ADHD-RS-5 for children/adolescents or AISRS for adults) 1
• Screen for suicidal ideation using the Columbia Suicide Severity Rating Scale (C-SSRS) 3
• Record height and weight 3

Follow-Up Monitoring

• Schedule follow-up at 2 weeks to assess early response, as most patients show improvement by this timepoint 1
• Reassess at 4 weeks with repeat ADHD rating scales 1
• Monitor blood pressure, pulse, height, and weight at each visit 3
• Continue C-SSRS monitoring, particularly during the first few months, as viloxazine ER carries a black box warning for suicidal ideation similar to atomoxetine 3, 6
• Schedule visits approximately every 3 months during maintenance treatment 3

Expected Efficacy Improvements

• Patients switching from atomoxetine to viloxazine ER demonstrate significantly greater improvement in both inattention and hyperactivity/impulsivity symptoms 1
• In pediatric patients, mean ADHD-RS-5 total scores improved from 33.1 on atomoxetine to 13.9 on viloxazine ER (p < 0.00001) 1
• In adults, mean AISRS total scores improved from 28.8 on atomoxetine to 11.9 on viloxazine ER (p = 0.0009) 1
• 96% of patients preferred viloxazine ER over atomoxetine in clinical practice 1

Side Effect Profile Comparison

Common Adverse Effects with Viloxazine ER

• Somnolence (9.5%), headache (8.9%), decreased appetite (6.0%), fatigue (5.7%), and nasopharyngitis (9.7%) 3
• Most adverse events are mild or moderate in severity, with only 3.9% reporting any severe adverse event 3
• Discontinuation rate due to adverse events is only 4% with viloxazine ER compared to 36% with atomoxetine 1

Atomoxetine Side Effects That May Improve

• Gastrointestinal upset, irritability, and fatigue are significantly more common with atomoxetine and often lead to discontinuation 1
• Six patients discontinued atomoxetine for GI upset, six for irritability, and five for fatigue in one comparative study 1
• Viloxazine ER appears better tolerated overall with fewer discontinuations 1

Mechanism of Action Differences

• Viloxazine ER is classified as a "serotonin norepinephrine modulating agent" with moderate activity at serotonin 5-HT2C receptors, representing a dual mechanism that differs from atomoxetine's pure norepinephrine reuptake inhibition 5
• This dual mechanism may explain the superior efficacy and faster onset compared to atomoxetine 4
• The serotonergic component may be particularly beneficial for patients with comorbid depression 4

Critical Safety Considerations

Serotonin Syndrome Risk

• Exercise caution when combining viloxazine ER with other serotonergic agents due to the risk of serotonin syndrome, particularly in the first 24-48 hours after starting or during dose adjustments 5
• If the patient is on any SSRIs or other serotonergic medications, monitor closely for signs of serotonin syndrome (agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, tremor) 5

Suicidal Ideation Monitoring

• Both atomoxetine and viloxazine ER carry black box warnings for suicidal ideation, so continue vigilant monitoring during the transition 3, 6
• The risk appears similar between the two medications, so switching does not eliminate this concern 5
• Use systematic C-SSRS screening at each visit, especially during the first few months 3

Cardiovascular Monitoring

• Monitor blood pressure and pulse at each visit, as both medications can cause modest increases in cardiovascular parameters 5, 3
• Viloxazine ER may cause increased blood pressure and increased pulse 5

Common Pitfalls to Avoid

• Do not assume viloxazine ER will take 4-6 weeks to work like atomoxetine—most patients respond within 2 weeks, so you can assess efficacy much earlier 1, 6
• Do not use an extended washout period beyond 5 days—this unnecessarily prolongs the time patients are without effective ADHD treatment 1
• Do not start at subtherapeutic doses—use the FDA-recommended starting doses of 100 mg for children or 200 mg for adolescents/adults 3
• Do not overlook the need for continued suicidal ideation monitoring—the black box warning applies to viloxazine ER just as it did to atomoxetine 3, 6

Special Populations

Patients with Comorbid Depression

• Viloxazine ER may be particularly beneficial for patients with comorbid depression due to its serotonergic modulation, as it was originally developed as an antidepressant 4
• This represents a potential advantage over atomoxetine, which despite initial development as an antidepressant, does not have evidence supporting efficacy for comorbid depression 5

Patients Who Failed Atomoxetine

• 85% of patients who switched from atomoxetine to viloxazine ER were able to taper off concurrent psychostimulants after stabilization on viloxazine ER, suggesting superior efficacy 1
• This makes viloxazine ER an excellent option for patients who had inadequate response to atomoxetine and required stimulant augmentation 1

Patients with Substance Use Concerns

• Both atomoxetine and viloxazine ER are non-controlled substances with no abuse potential, making them appropriate for patients with substance use history 5, 2
• The switch maintains this safety advantage while potentially improving efficacy 1

Long-Term Maintenance

• Viloxazine ER demonstrates sustained efficacy over long-term treatment with continued improvement beyond the initial response 3
• Mean ADHD-RS-IV/5 total score changes from baseline were -24.3 at Month 3, -26.1 at Month 12, and -22.4 at last study visit in long-term trials 3
• Median exposure in long-term studies was 260 days, with some patients treated for up to 1896 days (over 5 years) 3
• No new safety concerns emerged during long-term treatment, supporting the durability of the safety profile 3