Atomoxetine Causes More Fatigue Than Qelbree
Based on the highest quality direct comparison study, atomoxetine causes significantly more fatigue than viloxazine ER (Qelbree), with 36% of patients discontinuing atomoxetine due to side effects including fatigue (5 patients specifically), compared to only 4% discontinuing viloxazine ER due to fatigue. 1
Direct Comparative Evidence
The most recent and relevant head-to-head study provides clear evidence:
In a 2023 prospective study of 50 patients (35 children, 15 adults) who switched from atomoxetine to viloxazine ER, fatigue was a prominent discontinuation reason for atomoxetine (5 patients) but only caused 4% of patients to discontinue viloxazine ER 1
Overall, 36% of patients discontinued atomoxetine due to adverse effects (including GI upset, irritability, fatigue, and insomnia), while only 4% discontinued viloxazine ER 1
96% of patients preferred viloxazine ER over atomoxetine, with 86% reporting positive response to viloxazine ER by 2 weeks versus only 14% on atomoxetine 1
Side Effect Profile Comparison
Atomoxetine Fatigue Profile:
Fatigue and somnolence are well-established common adverse effects of atomoxetine, particularly during initial treatment or with rapid dose escalation 2, 3
Initial somnolence is specifically listed as a prominent side effect in pediatric patients with ADHD 2
Fatigue appears in multiple guideline summaries as a significant adverse effect requiring monitoring 4, 2, 3
Viloxazine ER Fatigue Profile:
Common adverse effects include somnolence and fatigue, but at apparently lower rates than atomoxetine 5
The direct comparison study showed minimal discontinuation due to fatigue with viloxazine ER 1
Clinical Implications
For patients experiencing fatigue on atomoxetine, switching to viloxazine ER represents a superior alternative:
Viloxazine ER demonstrates faster onset of action (1-2 weeks) compared to atomoxetine (4-6 weeks), potentially reducing the duration of side effect exposure 5
The improved tolerability profile of viloxazine ER allows for better medication adherence and symptom control 1
Important Caveats
Both medications carry FDA black box warnings for suicidal ideation in children and adolescents, requiring close monitoring regardless of which agent is chosen 2, 6, 5
CYP2D6 poor metabolizers (approximately 7% of Caucasians) experience significantly higher rates of adverse effects with atomoxetine, including fatigue, due to 10-fold higher drug exposure 2, 3
Split dosing of atomoxetine (morning and evening) or evening-only administration may reduce some side effects including initial somnolence, though this does not eliminate fatigue as a concern 2, 3