What are the guidelines for prescribing guanfacine (Alpha-2 adrenergic receptor agonist) for Attention Deficit Hyperactivity Disorder (ADHD) or hypertension?

Can You Prescribe Guanfacine?

Yes, you can prescribe guanfacine—it is FDA-approved for hypertension in adults and ADHD in children/adolescents aged 6-17 years, and it carries no controlled substance classification, eliminating DEA prescribing requirements. 1, 2

Regulatory Status and Prescribing Authority

• Guanfacine is not a controlled substance, meaning any licensed prescriber can write for it without DEA restrictions or concerns about abuse potential 1
• The immediate-release formulation is FDA-approved for hypertension management in adults, given alone or combined with other antihypertensives (especially thiazide diuretics) 2
• The extended-release formulation is FDA-approved specifically for ADHD treatment in pediatric patients aged 6-17 years 3, 1
• This non-controlled status makes guanfacine particularly appropriate for patients with substance use disorders or in high-diversion-risk environments like college settings 1

Clinical Indications

For ADHD (Extended-Release Formulation)

• Second-line treatment after stimulants due to smaller effect sizes (approximately 0.7 compared to placebo), though stimulants remain more effective 3
• First-line consideration in specific scenarios: comorbid substance use disorders, sleep disorders, or when stimulants are contraindicated 3, 1
• FDA-approved as adjunctive therapy with stimulants when monotherapy provides inadequate symptom control 3
• Works through alpha-2A adrenergic receptor agonism in the prefrontal cortex, not dopaminergic pathways, providing mechanistic distinction from stimulants 3, 1

For Hypertension (Immediate-Release Formulation)

• Reserved as last-line therapy due to significant CNS adverse effects, especially in older adults 4
• Classified among central alpha-2 agonists alongside clonidine and methyldopa 4
• Typical dosing: 0.5-2 mg once daily for hypertension 4

Dosing Guidelines

ADHD (Extended-Release)

• Starting dose: 1 mg once daily 3
• Target range: 0.05-0.12 mg/kg/day or 1-7 mg/day 3
• Titration: Increase by 1 mg per week based on response and tolerability 3
• Timing: Evening administration strongly preferred to minimize daytime somnolence that interferes with school/work performance 3
• Onset: Requires 2-4 weeks before clinical benefits appear—counsel families accordingly to prevent premature discontinuation 3

Hypertension (Immediate-Release)

• Starting dose: 1 mg daily at bedtime 2
• Maintenance: Most effect seen at 1 mg; may increase to 2 mg after 3-4 weeks if needed 2
• Maximum: Adverse reactions increase significantly above 3 mg/day 2

Critical Safety Warnings

Cardiovascular Monitoring

• Obtain baseline blood pressure and heart rate before initiation 3
• Monitor at each dose adjustment and periodically during maintenance 3
• Expect modest decreases: 1-4 mmHg BP and 1-2 bpm heart rate (opposite effect of stimulants) 3
• Screen for personal/family history of sudden cardiac death, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, or long QT syndrome 3

Discontinuation Protocol

• Never abruptly stop guanfacine—must taper by 1 mg every 3-7 days to avoid rebound hypertension 4, 3, 2
• Rebound hypertension occurs 2-4 days after abrupt cessation, delayed compared to clonidine due to longer half-life 2, 5
• In most cases, blood pressure returns to pretreatment levels slowly (within 2-4 days) without ill effects when properly tapered 2

Common Adverse Effects

• Most frequent: Somnolence/sedation, fatigue (15.2%), headache (20.5%), dry mouth, constipation (5-16% dose-dependent) 3
• Cardiovascular: Hypotension, bradycardia (generally mild but monitor closely) 3
• Rare but serious: Hallucinations, psychotic symptoms, cardiac conduction abnormalities 3
• All adverse effects typically mild-to-moderate, transient, and dose-related 3

Special Populations

Pregnancy

• Use with caution—limited safety data available 3
• One small study showed no congenital malformations but 20% of infants had low birth weight 3

Substance Use Disorders

• Preferred ADHD treatment due to non-controlled status and lack of abuse liability 1
• No risk of diversion, misuse, or tolerance development unlike stimulants 1
• Provides continuous symptom control without peaks/troughs that could trigger craving behaviors 1

Combination Therapy Considerations

• With stimulants: FDA-approved as adjunctive therapy; may increase treatment effects and/or decrease stimulant-related adverse effects like sleep disturbances 3
• With atomoxetine: Supported for inadequate symptom control 3
• With trazodone: Requires careful monitoring for excessive somnolence, hypotension, and bradycardia 3
• Never combine with clonidine: Both work through same alpha-2A mechanism; adding second alpha-2 agonist increases sedation/cardiovascular effects without clear efficacy benefit 3

Key Prescribing Pitfalls to Avoid

• Don't expect immediate results: Unlike stimulants that work immediately, guanfacine requires 2-4 weeks for therapeutic effect—set appropriate expectations 3
• Don't prescribe without cardiovascular screening: Baseline BP/HR mandatory, especially in patients with cardiac history 3
• Don't allow abrupt discontinuation: Always provide tapering instructions and warn patients about rebound hypertension risk 4, 3, 2
• Don't ignore orthostatic symptoms: Monitor for dizziness, especially in older adults or when combined with other antihypertensives 4
• Don't use as first-line for hypertension: Reserved as last-line due to CNS adverse effects 4