From the Guidelines
Guanfacine works for Attention Deficit Hyperactivity Disorder (ADHD) by agonizing alpha-2 adrenergic receptors, leading to enhanced noradrenergic neurotransmission in the prefrontal cortex, which strengthens the regulatory role of the prefrontal cortex in attention, thought, and working memory.
Mechanism of Action
- Guanfacine's mechanism of action is similar to clonidine, with both being alpha-2 adrenergic receptor agonists 1
- The agonistic effect on alpha-2 adrenergic receptors leads to a reduction in peripheral vascular resistance and consequently lower blood pressure 1
- In the prefrontal cortex, postsynaptic alpha-2 agonism enhances noradrenergic neurotransmission, strengthening the regulatory role of the prefrontal cortex in attention, thought, and working memory 1
Comparison to Other Medications
- Guanfacine is approximately ten times less potent than clonidine, with a higher specificity to alpha-2A receptors, which may mediate differences in adverse effects profiles, such as less sedative effects 1
- Guanfacine and clonidine have been shown to be efficacious in treating ADHD, but with smaller effect sizes compared to stimulants 1
- Guanfacine may be considered as a first-line treatment option in certain comorbidities, such as sleep disorders, substance use disorders, and disruptive behavior disorders 1
Clinical Use
- Guanfacine is approved as an extended-release formulation for the treatment of ADHD as a monotherapy or as an adjunctive therapy to stimulants in various countries 1
- The recommended dosing regimen for guanfacine is not specified in the provided evidence, but it is generally administered in the evening due to the relatively frequent occurrence of somnolence/fatigue as an adverse effect 1
- Guanfacine has been shown to have "around-the-clock" effects, with a slower onset of treatment effects compared to stimulants, typically taking 2-4 weeks to observe effects 1
From the FDA Drug Label
CLINICAL PHARMACOLOGY Guanfacine Tablets, USP are an orally active antihypertensive agent whose principal mechanism of action appears to be stimulation of central α 2-adrenergic receptors. The FDA drug label does not answer the question.
From the Research
Mechanism of Action
- Guanfacine is a selective α2A-adrenergic receptor agonist, which strengthens prefrontal cortical network connections, regulating attention, emotion, and behavior via the activity at post-synaptic α2A receptors 2.
- The beneficial actions of guanfacine are thought to be attributed to its ability to improve core symptoms of Attention Deficit Hyperactivity Disorder (ADHD) within 3 weeks with once-daily flexible dosing 3.
Efficacy in ADHD Treatment
- Guanfacine is an effective monotherapy treatment option for adults with ADHD, with current evidence suggesting its efficacy and safety 2.
- Guanfacine has been shown to be effective in treating ADHD in children and adolescents, with improvements in core symptoms and comorbid disorders such as autism, oppositional defiant behavior, and tics 4, 5.
- A meta-analysis of randomized controlled trials found that guanfacine was significantly more effective in treating ADHD compared to placebos, with a risk ratio of 1.78 (95% CI: 1.59-2.01) 6.
Safety and Side Effects
- Guanfacine has been found to be safe and effective for treating ADHD, with no serious adverse events reported 6.
- Common side effects of guanfacine include somnolence, headaches, and fatigue, with around 80% of participants in the guanfacine group experiencing at least one treatment-emergent adverse event (TEAE) 6.
- Guanfacine may provide a safe alternative therapy for children with ADHD in the presence of tics, with significant decreases in both commission errors and omission errors on the Continuous Performance Test (CPT) 5.