Viloxazine Adverse Effects and Clinical Considerations

Common Side Effects

Gastrointestinal symptoms, including nausea, vomiting, abdominal discomfort, and diarrhea, are the most commonly reported side effects, according to the American Academy of Child and Adolescent Psychiatry 1
Other common adverse effects include diaphoresis, dry mouth, dizziness, headache, tremor, insomnia, somnolence, decreased appetite, and weight loss, as reported by the American Academy of Child and Adolescent Psychiatry 1
Cardiovascular effects may include increased blood pressure and increased pulse, as noted by the American Academy of Child and Adolescent Psychiatry 1
Fatigue and somnolence have been reported with moderate strength of evidence, according to the American Academy of Child and Adolescent Psychiatry 2

Suicidal thinking and behavior (through age 24 years) is a potential risk, as with other antidepressants, as reported by the American Academy of Child and Adolescent Psychiatry 1
Other uncommon but potentially serious adverse effects include behavioral activation/agitation, hypomania, mania, sexual dysfunction, seizures, abnormal bleeding, and serotonin syndrome, according to the American Academy of Child and Adolescent Psychiatry 1

Viloxazine has been classified as a "serotonin norepinephrine modulating agent" with serotonin modulation potentially being an important component of its therapeutic effect 3, 4
Originally developed in the 1970s, viloxazine was used as an antidepressant in Europe for approximately 30 years, and was withdrawn from European markets in 2002 3, 4

For ADHD treatment, the extended-release formulation is typically started at 200 mg once daily 5
Can be titrated by 200 mg increments at weekly intervals based on response and tolerability 5
Maximum daily dose is 600 mg/day 5

Limited data is available regarding its use during pregnancy and breastfeeding, warranting caution in these populations 5, 6

Viloxazine 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, according to Pharmacology and Therapeutics 7
The American Academy of Child and Adolescent Psychiatry recommends caution when combining viloxazine with other serotonergic agents due to the risk of serotonin syndrome, particularly in the first 24-48 hours after starting or dose adjustments 8
Clinicians should be aware of the potential for suicidal thinking and behavior with viloxazine, although this risk appears lower than with atomoxetine, and monitor patients accordingly 8

Both atomoxetine and viloxazine ER may increase blood pressure and heart rate; therefore baseline vital signs should be recorded and re‑checked within 1–2 weeks after the switch. 10

Both agents carry warnings for suicidal ideation in children and adolescents; close observation for emergent suicidal thoughts is recommended throughout the transition period. 10

Unlike biologic therapies that often require a washout of roughly four drug half‑lives, non‑stimulant ADHD medications such as atomoxetine and viloxazine ER have no overlapping toxicities or dangerous pharmacodynamic interactions, so a formal washout period is unnecessary. 11, 12