What is the use and dosage of Guafacine (guanfacine) in treating attention deficit hyperactivity disorder (ADHD) and hypertension?

Guanfacine: Use and Dosage for ADHD and Hypertension

Guanfacine is FDA-approved for hypertension in adults and adolescents, while guanfacine extended-release is approved for ADHD in children and adolescents aged 6-17 years, functioning as a second-line non-stimulant option when stimulants are ineffective or not tolerated. 1, 2

Mechanism of Action

Guanfacine is an alpha-2A adrenergic receptor agonist that enhances noradrenergic neurotransmission in the prefrontal cortex, strengthening top-down guidance of attention, thought, and working memory. 2 It has higher specificity for alpha-2A receptors compared to clonidine, which explains its less sedative profile. 2

ADHD Treatment

Dosing for ADHD (Extended-Release Formulation)

Start with 1 mg once daily, preferably in the evening to minimize daytime somnolence and fatigue. 3, 2

• Titration schedule: Increase by 1 mg per week based on response and tolerability 3, 2
• Target dose range: 0.05 to 0.12 mg/kg/day or 1 to 7 mg/day 3, 2
• Weight-adjusted dosing: Approximately 0.1 mg/kg once daily 2
• Evening administration is strongly preferred because somnolence and fatigue are the most common adverse effects, and evening dosing minimizes daytime sedation that could interfere with school or work performance 2

Efficacy and Timeline

• Allow 2-4 weeks before observing clinical benefits, which is substantially longer than stimulants that work immediately 2
• Effect sizes compared to placebo are in the medium range (approximately 0.7), though stimulant medications remain more effective 2, 4
• Provides "around-the-clock" symptom control with once-daily dosing 2
• Current guidelines recommend guanfacine as second-line treatment after stimulants due to relatively smaller effect sizes 2

Combination Therapy

• Guanfacine extended-release is FDA-approved specifically for adjunctive therapy with stimulants, demonstrating safety in combination therapy 2
• Can be combined with atomoxetine (Strattera) with appropriate monitoring 2
• Never combine with clonidine, as adding a second alpha-2 agonist increases sedation risk and cardiovascular effects without clear evidence of superior efficacy 2

Hypertension Treatment

Dosing for Hypertension (Immediate-Release Formulation)

Start with 1 mg daily at bedtime to minimize somnolence. 1

• If inadequate response after 3-4 weeks: May increase to 2 mg daily 1
• Maximum effective dose: Most effects are seen at 1 mg; adverse reactions increase significantly with doses above 3 mg/day 1, 5
• Once-daily administration is sufficient due to long elimination half-life 5

Safety Profile and Monitoring

Cardiovascular Effects

• Monitor blood pressure and heart rate at baseline and during each dose adjustment, particularly important given modest reductions in both parameters 2, 6
• Dose-dependent decreases in blood pressure and heart rate are expected 7
• The physiologic response of increased blood pressure upon standing may be blunted in a dose-related manner 7

Common Adverse Effects

• Most common: Somnolence (38.6%), headache (20.5%), and fatigue (15.2%) 2, 4
• Other effects include dry mouth, dizziness, irritability, and abdominal pain, which are typically mild to moderate, transient, and dose-related 2
• Approximately 80% of patients experience at least one treatment-emergent adverse event compared to 66.5% with placebo 4

Critical Safety Warnings

Never abruptly discontinue guanfacine—it must be tapered to avoid rebound hypertension. 2, 1

• Taper schedule: Reduce by 1 mg every 3-7 days 2
• Rebound hypertension frequency is low but can occur 2-4 days after abrupt cessation, which is delayed compared to clonidine 1
• In most cases, blood pressure returns to pretreatment levels slowly (within 2-4 days) without ill effects when properly tapered 1

When to Contact Healthcare Provider Immediately

• Chest pain, very slow heart rate, or irregular heartbeat 2
• Accidental missed multiple doses—do not restart at full dose without medical guidance 2

Special Populations

Pregnancy and Breastfeeding

• Use with caution in pregnancy due to very limited safety data 3, 2
• One small study (n=30) in preeclampsia showed no congenital malformations, but all patients were outside the first trimester, and 20% of infants had low birth weight 3
• No published studies exist on guanfacine use while breastfeeding; alternative agents are preferred 3
• Guanfacine could be considered following a risk-benefit discussion, but alternative agents are preferred 3

Pediatric Considerations

• Approved in Canada for children and adolescents aged 6-17 years only 3
• Monitor ADHD symptoms systematically at each dose adjustment using parent and teacher reports 2
• Limited data exist on efficacy for ADHD treatment in adults 3

Clinical Pearls and Pitfalls

• Set appropriate expectations: The delayed 2-4 week onset of action is a critical counseling point to prevent premature discontinuation 2
• Consider guanfacine preferentially when tics coexist with ADHD, as it addresses both conditions simultaneously 8
• Guanfacine has a reasonable safety profile with less sedation than clonidine due to higher alpha-2A receptor specificity 8
• Baseline cardiovascular assessment is mandatory before initiation, especially when combining with other medications that affect blood pressure or heart rate 2