How does Qelbree (viloxazine) reduce dopamine in patients with attention deficit hyperactivity disorder (ADHD)?

Qelbree Does Not Reduce Dopamine—It Has Minimal Dopaminergic Activity

Qelbree (viloxazine) does not reduce dopamine; rather, it has only modest dopaminergic effects that are far less pronounced than traditional stimulants, while its primary mechanism involves norepinephrine reuptake inhibition and serotonin modulation. 1

Primary Mechanism of Action

Viloxazine functions primarily through two distinct pathways that do not involve dopamine reduction:

• Norepinephrine reuptake inhibition is the dominant mechanism, where viloxazine selectively blocks norepinephrine transporter (NET), preventing norepinephrine reuptake and increasing its availability in the prefrontal cortex 2, 3

• Serotonin modulation represents the second major pathway, with viloxazine acting as a selective 5-HT2B receptor antagonist and 5-HT2C receptor agonist, significantly increasing serotonin levels in the prefrontal cortex 1, 3

• This dual serotonin-norepinephrine mechanism distinguishes viloxazine from atomoxetine, which is a pure norepinephrine reuptake inhibitor without serotonergic activity 4, 1

Dopaminergic Effects Are Minimal, Not Reductive

The confusion about dopamine likely stems from comparing viloxazine to stimulants:

• Viloxazine elevates dopamine levels in the nucleus accumbens considerably less than traditional stimulant ADHD treatments, but this represents a smaller increase, not a reduction 2

• Microdialysis studies demonstrate that viloxazine "elicits moderate activity at dopaminergic systems, though this is not its primary mechanism" 1

• This minimal dopaminergic activity is actually advantageous, as it results in decreased potential for substance abuse, drug dependence, and withdrawal symptoms compared to stimulants 2

Clinical Implications

Understanding viloxazine's mechanism helps explain its clinical profile:

• The medication has been classified as a "serotonin norepinephrine modulating agent" (SNMA) rather than a dopaminergic agent 4, 3

• Clinicians should exercise caution when combining viloxazine with other serotonergic agents due to serotonin syndrome risk, particularly in the first 24-48 hours after initiation or dose adjustments 4, 1

• The lack of significant dopaminergic activity makes viloxazine particularly suitable for patients with comorbid substance use disorder, anxiety, or those who cannot tolerate stimulant side effects 5, 6