guanfacine

General Information

Guanfacine immediate-release (brand Tenex; generic tablets) is a centrally acting alpha-2 adrenergic agonist approved for hypertension (label).

In psychiatric settings, guanfacine is sometimes used off-label as an adjunct when symptoms include hyperarousal, irritability, or anxiety-related insomnia and lowering sympathetic activation is part of the treatment target (clinical practice pattern).

Compared with clonidine, guanfacine is generally considered more selective for alpha-2A receptors and often causes less sedation, but fatigue, dizziness, and hypotension can still be clinically limiting, especially early in treatment and with polypharmacy (label/class).

Abrupt discontinuation can cause rebound hypertension and agitation. Rebound may be delayed for several days (reported 2–4 days after stopping), so taper planning and refill continuity matter (label).

The guanfacine compare view, evidence feed, and print page support side-by-side review and patient-friendly handouts for monitoring and taper planning.

Guanfacine is not a controlled substance. In psychiatry it is usually positioned as an adjunct for autonomic hyperarousal symptoms or hyperarousal-linked insomnia rather than a first-line long-term strategy for primary anxiety disorders.

Mechanism of Action

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

Alpha-2 adrenergic agonism reduces central sympathetic outflow and lowers blood pressure and heart rate.

In psychiatric practice, the same mechanism can reduce physical anxiety symptoms (autonomic arousal) and support sleep when nighttime hyperarousal is prominent (clinical practice pattern).

Sedation and dizziness reflect central and peripheral alpha-2 effects; titration speed, dose timing, and the broader sedative burden are practical levers to improve tolerability.

• Alpha-2 adrenergic agonist (alpha-2A preferential, class-level).
• Not a stimulant; no euphoric effect; not controlled.

Metabolism and Pharmacokinetics

• Average elimination half-life is ~17 hours (range 10–30 hours) in individuals with normal renal function (label).
• Guanfacine and metabolites are excreted primarily in urine; ~50% (range 40–75%) is eliminated in urine as unchanged drug (label).
• Rebound hypertension can occur after abrupt discontinuation and may be delayed 2–4 days, consistent with the longer half-life compared with clonidine (label).
• Concomitant microsomal enzyme inducers have been reported to reduce elimination half-life and plasma concentrations in some patients (label).

Dosing and Administration

• Hypertension labeling: start 1 mg once daily at bedtime to minimize somnolence; if response is inadequate after 3–4 weeks, 2 mg once daily may be used (label).
• For off-label psychiatric use, clinicians often individualize dosing to blood pressure/heart rate, daytime alertness, and the desired timing of effect (e.g., bedtime dosing when insomnia is the main symptom) (clinical practice pattern).
• Avoid abrupt discontinuation after regular use; gradual tapering is commonly used to reduce rebound hypertension and agitation (label/class).

Monitoring & Labs

• Baseline and periodic blood pressure and heart rate, especially during titration.
• Sedation, dizziness, and orthostasis; reassess driving, falls risk, and daytime functioning.
• Review co-prescribed antihypertensives and sedatives at initiation and dose changes.
• Document a taper plan early to reduce abrupt discontinuation and rebound hypertension risk.

Adverse Effects

Interactions

• Additive hypotension or bradycardia can occur with other antihypertensive drugs; symptomatic dizziness or syncope should prompt medication review and vitals monitoring (label/class).
• Additive CNS depression can occur with alcohol, opioids, hypnotics, and sedating antipsychotics; total sedative burden is a major driver of harm (label/class).
• Microsomal enzyme inducers have been reported to reduce guanfacine exposure in some patients; if efficacy drops after adding an inducer, reassess rather than escalating dose without monitoring (label).

Other Useful Information

• Guanfacine immediate-release is distinct from guanfacine ER (Intuniv); the ER product is the formulation labeled and studied for ADHD, and the two are not interchangeable milligram-for-milligram (label/guidelines).
• When insomnia is the main complaint, compare guanfacine with non-blood pressure lowering options (e.g., DORAs, ramelteon, low-dose doxepin) and prioritize behavioral strategies such as CBT-I for chronic insomnia.
• When anxiety remains frequent, the primary treatment is usually psychotherapy and/or SSRI/SNRI therapy; alpha-2 agonists are typically adjuncts for physical symptoms rather than a core long-term strategy.

References

1. Guanfacine tablets 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)