What is the recommended dosage of guanfacine (alpha-2 adrenergic receptor agonist) for the treatment of Attention Deficit Hyperactivity Disorder (ADHD)?

Guanfacine Dosing for ADHD

Start guanfacine extended-release at 1 mg once daily, titrate by 1 mg per week based on response and tolerability, targeting a weight-adjusted dose of 0.05-0.12 mg/kg/day (typically 1-4 mg/day maximum in most contexts, though up to 7 mg/day has been used). 1, 2

Initial Dosing Strategy

• Begin with 1 mg once daily, regardless of age or weight, to minimize initial adverse effects 1, 2, 3
• Administer in the evening rather than morning to mitigate daytime somnolence and sedation, which are the most common side effects 1, 2
• Available tablet strengths are 1,2,3, and 4 mg extended-release formulations 1, 2

Titration Protocol

• Increase by 1 mg per week based on clinical response and tolerability 1, 2, 3
• Target the weight-adjusted range of 0.05-0.12 mg/kg/day, which translates to a general rule of thumb of 0.1 mg/kg once daily 1, 2
• The maximum recommended dose is 4 mg daily in most clinical contexts, though doses up to 7 mg/day have been documented in some guidelines 1, 3
• Monitor ADHD symptoms systematically at each dose adjustment using parent and teacher reports 2

Expected Timeline for Response

• Expect 2-4 weeks before observing clinical benefits, unlike stimulants which work immediately 1, 2, 3
• This delayed onset is critical for patient/family counseling to prevent premature discontinuation 2
• Improvements in ADHD symptoms and functional impairment have been sustained over 24 months in open-label extension trials 2, 4

Treatment Positioning

• Guanfacine is second-line after stimulants, with effect sizes around 0.7 compared to placebo (versus ~1.0 for stimulants) 1, 2
• May be used as adjunctive therapy with stimulants when stimulant monotherapy provides inadequate symptom control 1, 2
• Both guanfacine and clonidine extended-release are FDA-approved specifically for adjunctive use with stimulants 2

Age-Specific Recommendations

• Approved for children and adolescents aged 6-17 years 1, 4, 5
• Not recommended for preschool-aged children (4-5 years) due to insufficient rigorous study in this population 1
• In Canada, approval is specifically limited to ages 6-17 years 1

Cardiovascular Monitoring Requirements

• Obtain baseline blood pressure and heart rate before initiation 1, 2
• Obtain personal and family cardiac history; consider ECG if risk factors are present 1
• Monitor vital signs regularly during dose adjustments, as guanfacine causes dose-dependent decreases in blood pressure and heart rate 1, 2, 5, 6
• Cardiovascular effects are generally modest but require monitoring for hypotension and bradycardia 1, 2, 7

Common Adverse Effects

• Somnolence/sedation (most common), headache (20.5%), and fatigue (15.2%) 2, 4, 5
• Additional effects include dizziness, irritability, dry mouth, abdominal pain, constipation (5-16%), and nausea 1, 2, 5
• Most adverse events are mild to moderate, dose-related, and transient, typically emerging within the first 2 weeks and resolving over time 2, 4, 5, 7
• These effects do not typically interfere with attention or overall efficacy 5, 8

Critical Safety Warnings

• Never abruptly discontinue guanfacine—it must be tapered by 1 mg every 3-7 days to avoid rebound hypertension 1, 2
• This tapering requirement applies even when switching medications or if the patient misses multiple doses 2
• Rare but serious effects include hallucinations, psychotic symptoms, and cardiac conduction abnormalities 2

Special Populations

• Pregnancy: Use with caution; alternative agents preferred when possible due to limited safety data (one small study showed 20% low birth weight) 1, 2
• Breastfeeding: No published studies available 1
• CYP3A4 interactions: Guanfacine is primarily metabolized via CYP3A4, requiring dose adjustments with strong inhibitors or inducers 1, 3

Practical Considerations

• Guanfacine provides "around-the-clock" symptom control with once-daily dosing, unlike shorter-acting stimulants 2
• Higher specificity for alpha-2A receptors compared to clonidine may result in fewer sedative effects 1, 2
• In Europe, guanfacine is only approved when stimulants are not suitable, not tolerated, or ineffective 1, 3
• Do not combine with clonidine, as adding a second alpha-2 agonist increases sedation and cardiovascular risks without clear evidence of superior efficacy 2