From the Guidelines
The non-stimulant medications clonidine, guanfacine, atomoxetine, bupropion, and viloxazine are used to treat ADHD and other conditions, with distinct mechanisms of action and side effect profiles. These medications can be classified into different classes, including alpha-2 adrenergic agonists (clonidine and guanfacine) and norepinephrine reuptake inhibitors (atomoxetine, bupropion, and viloxazine).
- Clonidine and guanfacine work by stimulating alpha-2 receptors in the prefrontal cortex, enhancing norepinephrine signaling and improving executive function, with common side effects including sedation, dry mouth, dizziness, and potential hypotension 1.
- Atomoxetine is a selective norepinephrine reuptake inhibitor that increases norepinephrine and dopamine in the prefrontal cortex, typically dosed at 40-100mg daily with side effects including nausea, decreased appetite, and rare liver effects 1.
- Bupropion, an aminoketone antidepressant, inhibits norepinephrine and dopamine reuptake (150-450mg daily) with side effects including insomnia, headache, and seizure risk at higher doses 1.
- Viloxazine, a newer norepinephrine reuptake inhibitor (100-400mg daily), can cause somnolence, headache, and decreased appetite 1. The choice of medication depends on individual patient needs, comorbidities, and potential side effects, with clonidine and guanfacine often used for patients with anxiety, tics, or substance use disorders, and atomoxetine, bupropion, and viloxazine used for patients who cannot tolerate stimulants or have specific comorbid conditions 1. These medications generally take longer to show full effects compared to stimulants (2-6 weeks) and require gradual titration to minimize side effects, offering important alternatives for patients with ADHD and other conditions 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Class of Drugs
- Clonidine: alpha2-adrenergic agonist 2
- Guanfacine: alpha2-adrenergic agonist 3, 2
- Bupropion: norepinephrine-dopamine reuptake inhibitor (NDRI) 4
- Viloxazine: selective norepinephrine reuptake inhibitor (NRI) and serotonin-norepinephrine modulating agent (SNMA) 5, 6
- Atomoxetine: selective norepinephrine reuptake inhibitor (NRI) 5, 4
Mechanism of Action
- Clonidine: stimulates alpha2-adrenergic receptors, decreasing the release of norepinephrine and increasing the activity of inhibitory neurons 2
- Guanfacine: stimulates alpha2-adrenergic receptors, decreasing the release of norepinephrine and increasing the activity of inhibitory neurons 3, 2
- Bupropion: inhibits the reuptake of norepinephrine and dopamine, increasing the levels of these neurotransmitters in the brain 4
- Viloxazine: inhibits the reuptake of norepinephrine, increasing the levels of this neurotransmitter in the brain, and modulates serotonergic activity 5, 6
- Atomoxetine: inhibits the reuptake of norepinephrine, increasing the levels of this neurotransmitter in the brain 5, 4
Common Side Effects
- Clonidine: somnolence, headaches, fatigue 2
- Guanfacine: somnolence (38.6%), headaches (20.5%), fatigue (15.2%) 3
- Bupropion: not specified in the provided studies
- Viloxazine: not specified in the provided studies
- Atomoxetine: not specified in the provided studies, but associated with improved patient-reported clinical response and quality of life compared with placebo 4