What is the use and dosage of Guanfacine?

Guanfacine: Uses and Dosing

Guanfacine is FDA-approved for hypertension in adults, but is widely used off-label and supported by major pediatric guidelines for ADHD treatment in children and adolescents aged 6-17 years, with dosing of 1-7 mg/day (0.05-0.12 mg/kg/day) given once daily, preferably in the evening. 1, 2, 3

Primary Indications

FDA-Approved Use

• Hypertension management in adults, given alone or combined with other antihypertensives (especially thiazide diuretics), starting at 1 mg daily at bedtime 3

Guideline-Supported ADHD Use

• First-line ADHD treatment in specific populations: patients with comorbid substance use disorders (due to non-controlled status), disruptive behavior disorders (oppositional defiant disorder, conduct disorder), tic disorders/Tourette's syndrome, or significant sleep disturbances 2, 4
• Second-line ADHD treatment when stimulants fail, are not tolerated, or cause unacceptable side effects (appetite suppression, growth concerns, cardiovascular effects, sleep problems) 1, 4
• Adjunctive therapy with stimulants (FDA-approved in USA) to enhance efficacy or reduce stimulant-related adverse effects, particularly sleep disturbances 1, 4

Dosing Guidelines

ADHD Dosing (Extended-Release)

• Starting dose: 1 mg once daily 1
• Titration: Increase by 1 mg weekly based on response and tolerability 1
• Target range: 0.05-0.12 mg/kg/day or 1-7 mg/day 1
• Timing: Evening administration strongly preferred to minimize daytime somnolence and fatigue 1, 4
• Onset of effect: Requires 2-4 weeks before clinical benefits observed, unlike stimulants which work immediately 1, 4

Hypertension Dosing (Immediate-Release)

• Starting dose: 1 mg daily at bedtime 3
• Titration: May increase to 2 mg after 3-4 weeks if inadequate response 3
• Maximum: Doses above 3 mg/day significantly increase adverse reactions 3

Mechanism of Action

• Alpha-2A adrenergic receptor agonist that enhances noradrenergic neurotransmission in the prefrontal cortex, strengthening top-down regulation of attention, thought, and working memory 1
• Works through alpha-2A receptors rather than affecting dopamine/norepinephrine reuptake, with higher alpha-2A specificity than clonidine, resulting in less sedation 1, 4

Critical Safety Considerations

Cardiovascular Monitoring

• Obtain baseline blood pressure and heart rate before initiation 1, 4
• Monitor at each dose adjustment and periodically during maintenance 1, 4
• Expect modest decreases: 1-4 mmHg in blood pressure, 1-2 bpm in heart rate 1, 4
• Screen for personal/family cardiac history including sudden death, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, long QT syndrome 1

Discontinuation Protocol

• Never abruptly stop guanfacine—must taper by 1 mg every 3-7 days to avoid rebound hypertension 1, 2, 4
• Rebound occurs 2-4 days after abrupt cessation (delayed compared to clonidine due to longer half-life) 3, 5

Common Adverse Effects

• Somnolence/sedation (most common—mitigated by evening dosing) 1, 6, 7
• Headache (20.5% of patients) and fatigue (15.2%) 1
• Dry mouth, dizziness, constipation (5-16%, dose-dependent), irritability, abdominal pain 1
• Hypotension and bradycardia (monitor during dose adjustments) 1, 4

Clinical Advantages

• Non-controlled substance status: No DEA requirements, no abuse liability, no diversion risk—particularly valuable in substance use disorder populations 2, 4
• Once-daily dosing with extended-release formulation provides around-the-clock symptom control without peaks/troughs 1, 4
• Long-term efficacy: Improvements sustained over 24 months in open-label trials 1, 7
• May improve comorbid symptoms: Oppositional behaviors, tics (does not worsen them like stimulants can), sleep disturbances 4

Important Caveats

• Effect sizes are medium range (approximately 0.7 vs placebo), smaller than stimulants in head-to-head trials 1, 4
• Delayed therapeutic onset (2-4 weeks) requires patient/family counseling to prevent premature discontinuation 1, 4
• 5-15% of patients may experience substantial blood pressure/heart rate decreases requiring closer monitoring 1
• Rare but serious: hallucinations, psychotic symptoms, cardiac conduction abnormalities 1

Special Populations

• Pregnancy: Use with caution due to limited safety data; one small study showed no congenital malformations but 20% low birth weight 1
• Substance use disorders: Specifically recommended first-line due to non-dopaminergic mechanism and lack of abuse potential 2, 4
• Intellectual disability with ADHD: Can be considered when stimulants fail, though evidence limited and monitor for depression, sleep disturbance, cognitive dulling 4

When to Contact Provider Immediately

• Chest pain, very slow heart rate, or irregular heartbeat 1
• Accidentally missing multiple doses (do not restart at full dose without medical guidance) 1