What is the use of Guanfacine (Intuniv)

From the Guidelines

Guanfacine is recommended as a second-line treatment for attention deficit hyperactivity disorder (ADHD) in children and adults, with a typical starting dose of 1 mg once daily, potentially increasing to 1-7 mg daily, due to its efficacy in reducing core symptoms and improving functional impairment and quality of life 1.

Key Points

• Guanfacine works as a selective alpha-2A adrenergic receptor agonist, decreasing sympathetic outflow from the brain which improves attention and reduces impulsivity in ADHD and lowers blood pressure in hypertension.
• Common side effects include drowsiness, fatigue, dry mouth, constipation, and dizziness.
• The medication should be taken consistently, and abrupt discontinuation should be avoided as it may cause rebound hypertension.
• Guanfacine may interact with other medications that affect blood pressure or cause sedation, so a complete medication review is important before starting treatment.
• Guanfacine has been shown to be effective in reducing core symptoms of ADHD, with an effect size of approximately 0.7, although this is smaller than that of stimulant medications 1.

Considerations

• Guanfacine is not approved for use in preschool-aged children, and its use in this population is not recommended due to limited evidence and potential risks 1.
• Guanfacine may be considered as an adjunctive therapy to stimulant medications, which can increase treatment effects and/or decrease adverse effects of stimulants, particularly sleep disturbances and cardiovascular effects 1.
• Guanfacine has been shown to be effective in improving functional impairment and quality of life in patients with ADHD, and may be considered as a first-line treatment option in certain cases, such as in patients with comorbid substance use disorders or sleep disorders 1.

From the FDA Drug Label

Guanfacine tablets are indicated in the management of hypertension. Guanfacine tablets may be given alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

Guanfacine Tablets, USP are an orally active antihypertensive agent whose principal mechanism of action appears to be stimulation of central α 2-adrenergic receptors. By stimulating these receptors, guanfacine reduces sympathetic nerve impulses from the vasomotor center to the heart and blood vessels This results in a decrease in peripheral vascular resistance and a reduction in heart rate.

Guanfacine is used for the management of hypertension. It can be given alone or in combination with other antihypertensive agents, especially thiazide-type diuretics. The mechanism of action is through stimulation of central α 2-adrenergic receptors, which reduces sympathetic nerve impulses and results in a decrease in peripheral vascular resistance and a reduction in heart rate 2 2.

• Key uses:
  • Management of hypertension
  • Can be used alone or in combination with other antihypertensive agents
• Mechanism of action:
  • Stimulation of central α 2-adrenergic receptors
  • Reduction of sympathetic nerve impulses
  • Decrease in peripheral vascular resistance and heart rate

From the Research

Guanfacine Use

• Guanfacine, an alpha(2A) adrenoceptor agonist, is U.S. Food and Drug Administration (FDA)-approved for the treatment of hypertension in adolescents and adults, and has been used "off-label" for several years in children as a possible treatment for attention-deficit/hyperactivity disorder (ADHD) and pervasive developmental disorders (PDDs) 3.
• Small placebo-controlled trials support the use of guanfacine for the treatment of ADHD, with the most common adverse effects associated with guanfacine and guanfacine extended release (GXR) treatment being sedation 3.
• Guanfacine extended release (GXR) has reported efficacy for the treatment of ADHD as monotherapy and adjunctive therapy to psychostimulant medications, with a safety profile consistent with that of a centrally acting α2A-adrenoceptor agonist 4.
• Studies have demonstrated that GXR is an effective treatment option for children and adolescents with ADHD, with adverse events (AEs) typically mild to moderate, although severe AEs and discontinuations due to AEs have been observed 4, 5.

Efficacy and Safety

• A meta-analysis of 12 randomized controlled trials (RCTs) 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) 5.
• The most common treatment-emergent adverse events (TEAEs) in the guanfacine group were somnolence (38.6%), headaches (20.5%), and fatigue (15.2%) 5.
• A long-term, open-label, phase 3 extension study found that GXR was safe and effective for the treatment of ADHD in adults, with significant improvements in ADHD symptoms, quality of life, and executive functioning 6.

Guanfacine in Adults

• Guanfacine extended-release (GXR) is a non-psychostimulant ADHD drug that is a selective α2A-adrenergic receptor agonist, first approved for treatment of adult ADHD in Japan in June 2019 7.
• Current evidence suggests that GXR is an effective monotherapy treatment option for adults with ADHD, with a beneficial action thought to be attributed to the strengthening of prefrontal cortical network connections 7.
• A study found that GXR was safe and effective for the treatment of ADHD in adults, with common TEAEs including somnolence, thirst, nasopharyngitis, and decreased blood pressure 6.