guanfacine ER

General Information

Guanfacine extended-release (ER) is a non-stimulant ADHD medication and an alpha-2A adrenergic agonist. It is often used when stimulants are poorly tolerated or when tics, anxiety, insomnia, or diversion concerns complicate stimulant prescribing.

It is sometimes used as an adjunct to stimulants when focus improves but residual impulsivity, emotional reactivity, or sleep-onset problems remain prominent.

When combined with stimulants, guanfacine ER is often used to target hyperactivity, impulsivity, and evening rebound while allowing lower stimulant doses in patients who develop insomnia or anxiety.

In serious mental illness, guanfacine ER may be appealing when stimulant activation risk is high, but hypotension, bradycardia, and additive sedation with other CNS depressants remain key monitoring targets.

The guanfacine ER compare view, the evidence feed, and the print page support side-by-side review and patient-friendly handouts for titration and tapering.

The most common reasons guanfacine ER fails are sedation that is not managed with dosing timing/titration speed and discontinuation without a taper (rebound symptoms). When used thoughtfully, it can reduce hyperactivity and impulsivity while supporting sleep and reducing the need for higher stimulant doses.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Alpha-2A adrenergic agonism reduces noradrenergic signaling in prefrontal circuits and can improve working memory, impulse control, and emotional regulation.

Unlike stimulants, it does not directly increase dopamine release and has no meaningful euphoric effect; misuse risk is lower.

Sedation and hypotension reflect central and peripheral alpha-2 effects; titration speed and dose timing are practical levers to improve tolerability.

• Alpha-2A adrenergic agonist (primary).
• No direct stimulant release mechanism; not a controlled substance.

Metabolism and Pharmacokinetics

• Metabolized primarily via CYP3A4; inhibitors can increase exposure and adverse effects.
• Half-life is long enough for once-daily dosing; clinical sedation often tracks peak exposure early in treatment.
• Renal/hepatic impairment and interacting medications can increase hypotension and fatigue risk.

Dosing and Administration

• Typically once daily. Morning dosing is common, but bedtime dosing can be considered when sedation is prominent.
• Dosing typically starts low and titrates weekly as tolerated. Typical doses are 1–4 mg/day (product- and age-dependent).
• If daytime fatigue or dizziness limits function, slower titration, dose reduction, or evening dosing are common adjustments before concluding the trial is not tolerated.
• Abrupt discontinuation can lead to rebound hypertension, tachycardia, and irritability; a taper is typically used to reduce this risk.

Monitoring & Labs

• Baseline and periodic blood pressure and heart rate, especially during titration.
• Sedation, dizziness, and orthostasis are commonly monitored; dose timing and titration speed are adjusted as needed.
• Interacting medications (CYP3A4 inhibitors/inducers) and other sedatives are typically reviewed.
• Taper planning in advance can reduce rebound hypertension and irritability.

Sources: DailyMed label; guideline statements; network meta-analysis context.

Adverse Effects

Interactions

• CYP3A4 inhibitors can increase exposure and worsen hypotension/sedation; CYP3A4 inducers may reduce efficacy.
• Additive hypotension or sedation can occur with other antihypertensives and CNS depressants (including alcohol).

Other Useful Information

• Guanfacine ER is often considered when stimulants improve focus but impulsivity or emotional reactivity remains problematic, or when tics/anxiety limit stimulant dose.
• When sedation is the main adverse effect, slower titration and dose-timing adjustments are common first steps rather than adding stimulants back solely to counter fatigue.
• Baseline blood pressure and heart rate are commonly documented and revisited after each dose change.
• In polypharmacy (e.g., multiple sedating agents or antihypertensives), a single taper plan is often documented and communicated across care transitions to reduce abrupt discontinuation and rebound symptoms.

References

1. Intuniv (guanfacine Extended Release) Prescribing Information — DailyMed (2025)
2. Attention deficit hyperactivity disorder (NICE guideline NG87) — NICE (2018)
3. Clinical Practice Guideline FOR THE Diagnosis, Evaluation, AND Treatment OF Attention Deficit/hyperactivity Disorder IN Children AND Adolescents — Pediatrics (2019)
4. Comparative Efficacy AND Tolerability OF Medications FOR Adhd (systematic Review AND Network Meta Analysis) — Lancet Psychiatry (2018)