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This entry describes a combination therapy of **viloxazine** (typically as viloxazine extended-release, VLX-ER) and a **psychostimulant** (most commonly methylphenidate or amphetamine-derived stimulant). This approach is used in children and adolescents with **ADHD** who have inadequate response to psychostimulant monotherapy. Viloxazine is a serotonin-norepinephrine modulating agent (SNMA) with actions as a selective 5-HT2B receptor antagonist, 5-HT2C receptor agonist, and moderate norepinephrine transporter (NET) inhibitor, leading to increased availability of norepinephrine and serotonin in the prefrontal cortex. Psychostimulants (e.g., methylphenidate, amphetamines) predominantly block the reuptake of dopamine and norepinephrine (by inhibiting DAT and NET), increasing their availability in key brain regions. The combination offers additive or synergistic effects on ADHD symptom control, and clinical research indicates this combination is generally well tolerated and efficacious, showing improvements in ADHD symptom scales without additional pharmacokinetic interactions or significant safety concerns beyond those already known for the individual agents[1][2][3][4][5].
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