From the Guidelines
Clonidine and guanfacine are alpha-2 adrenergic agonists, viloxazine and atomoxetine are norepinephrine reuptake inhibitors, and bupropion is a norepinephrine-dopamine reuptake inhibitor, each with distinct mechanisms of action and adverse effect profiles.
Mechanism of Action and Adverse Effects
- Clonidine and guanfacine work by agonistically affecting alpha-2 adrenergic receptors, leading to reduced peripheral vascular resistance and enhanced noradrenergic neurotransmission in the prefrontal cortex 1.
- Viloxazine and atomoxetine increase norepinephrine levels in the synaptic cleft by inhibiting its reuptake, thereby improving attention and impulse control.
- Bupropion blocks the reuptake of norepinephrine and dopamine, enhancing their activity.
Key Adverse Effects
- Clonidine and guanfacine: sedation, dry mouth, hypotension, bradycardia, and rebound hypertension if stopped abruptly 1.
- Viloxazine and atomoxetine: nausea, decreased appetite, insomnia, and rarely, increased blood pressure and heart rate.
- Atomoxetine carries a black box warning for suicidal ideation in children and adolescents 1.
- Bupropion: insomnia, headache, dry mouth, nausea, and a dose-dependent risk of seizures, with a black box warning for increased suicidality in young patients.
Clinical Use
- These medications are used for various conditions, including ADHD, hypertension, withdrawal syndromes, depression, and smoking cessation.
- The choice of medication should be based on the individual patient's needs, medical history, and potential for adverse effects, with careful consideration of the benefits and risks.
- It is essential to monitor patients closely for adverse effects, especially when initiating or adjusting medications, and to provide education on potential side effects and their management.
From the FDA Drug Label
The mechanism of action of bupropion is unknown, as is the case with other antidepressants. However, it is presumed that this action is mediated by noradrenergic and/or dopaminergic mechanisms. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine and does not inhibit monoamine oxidase or the reuptake of serotonin. ADVERSE REACTIONS Adverse reactions noted with guanfacine hydrochloride are similar to those of other drugs of the central α 2-adrenoreceptor agonist class: dry mouth, sedation (somnolence), weakness (asthenia), dizziness, constipation, and impotence.
- Bupropion:
- Class: Antidepressant of the aminoketone class
- Mechanism of Action: Unknown, presumed to be mediated by noradrenergic and/or dopaminergic mechanisms
- Key Adverse Effects: Hallucinations, loss of consciousness, mental status changes, sinus tachycardia, ECG changes, clonus, myoclonus, hyperreflexia, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure 2
- Guanfacine:
- Class: Central α 2-adrenoreceptor agonist
- Mechanism of Action: Stimulates central α 2-adrenoreceptors
- Key Adverse Effects: Dry mouth, sedation (somnolence), weakness (asthenia), dizziness, constipation, and impotence 3
The FDA drug label does not provide information on clonidine, viloxazine, or atomoxetine.
From the Research
Class and Mechanism of Action
- Clonidine and guanfacine are alpha-2 agonists, which work by stimulating alpha-2 adrenergic receptors in the brain, resulting in decreased sympathetic outflow and a subsequent decrease in blood pressure and heart rate 4, 5, 6, 7.
- Viloxazine is a norepinephrine reuptake inhibitor, which increases the levels of norepinephrine in the brain by blocking its reabsorption 8.
- Atomoxetine is a selective norepinephrine reuptake inhibitor, which increases the levels of norepinephrine in the brain by blocking its reabsorption 8.
- Bupropion is a norepinephrine-dopamine reuptake inhibitor, which increases the levels of norepinephrine and dopamine in the brain by blocking their reabsorption.
Key Adverse Effects
- Clonidine: sedation, hypotension, dry mouth, drowsiness, and fatigue 4, 5, 6, 7.
- Guanfacine: sedation, hypotension, dry mouth, drowsiness, and fatigue, although it may have a more favorable side effect profile compared to clonidine 4, 5, 6, 7.
- Viloxazine: gastrointestinal upset, irritability, fatigue, and insomnia, although it may have a more favorable side effect profile compared to atomoxetine 8.
- Atomoxetine: gastrointestinal upset, irritability, fatigue, insomnia, and appetite suppression 8.
- Bupropion: insomnia, dry mouth, nausea, headache, and anxiety.
Comparison of Medications
- Clonidine and guanfacine may be less efficacious than stimulants for the treatment of ADHD, but they have the advantage of not being controlled substances and having no known abuse potential 4.
- Viloxazine may be more effective than atomoxetine in improving inattention and hyperactivity/impulsivity in patients with ADHD, with a more favorable side effect profile 8.
- Atomoxetine and bupropion may be more effective than clonidine and guanfacine in improving inattention, but they may have a higher risk of side effects such as gastrointestinal upset and insomnia 8.