Which ADHD medication is a selective norepinephrine reuptake inhibitor (non-stimulant)?

• A. Atomoxetine
• B. Guanfacine
• C. Clonidine
• D. Bupropion

Answer: (A)

Atomoxetine is the non-stimulant ADHD medication that works by selectively blocking the norepinephrine transporter, increasing norepinephrine in the synaptic cleft. This boost in NE is particularly impactful in the prefrontal cortex, where enhanced noradrenergic signaling improves attention, working memory, and behavioral control. Because its action is targeted to norepinephrine rather than dopamine in reward pathways, it has less stimulant-like potential and abuse risk compared with stimulant medications. It often takes several weeks to reach full effect, and patients may experience side effects such as stomach upset, decreased appetite, sleep disturbances, or fatigue, with a boxed warning for suicidality in young people and rare risk of liver injury.

Guanfacine and clonidine are alpha-2 adrenergic agonists that modulate norepinephrine signaling through feedback inhibition, not by inhibiting reuptake. Bupropion inhibits both dopamine and norepinephrine reuptake, so it’s not selective for norepinephrine.