Central alpha-2 adrenergic agonists

Clonidine & Guanfacine

Catapres (clonidine IR), Kapvay (clonidine ER), Tenex (guanfacine IR), Intuniv (guanfacine ER)
FDA-Approved Indications
  • ADHD (clonidine ER / Kapvay; guanfacine ER / Intuniv), as monotherapy or adjunct to stimulants
  • Hypertension (clonidine IR)
Common Off-Label Uses
  • Opioid withdrawal symptom management (clonidine)
  • PTSD-related hyperarousal and nightmares (both)
  • Insomnia (both, particularly in children/adolescents with ADHD)
  • Tic disorders (both)
  • Aggression/irritability adjunct in children (guanfacine)
  • Autonomic hyperarousal in anxiety

Side Effects Worth Knowing

Sedation/drowsiness: very common, especially at initiation

The most frequently reported side effect. Often improves over weeks. Bedtime dosing minimizes daytime impact. More prominent with clonidine than guanfacine. Can be treatment-limiting, particularly in students and working adults.

Hypotension: dose-dependent

Expected pharmacological effect. Usually asymptomatic at psychiatric doses but can cause dizziness, lightheadedness, or syncope, particularly with rapid dose titration, concurrent antihypertensives, or dehydration. Monitor blood pressure.

Bradycardia: dose-dependent

Reduced sympathetic tone lowers heart rate. Usually asymptomatic at standard doses. Monitor heart rate, particularly when combined with beta-blockers or other medications that slow heart rate.

Dry mouth: common

Alpha-2 agonist effect on salivary glands. Usually mild and tolerable.

Rebound hypertension on discontinuation: critical safety concern

Abrupt cessation after chronic use can trigger sympathetic rebound. More pronounced with clonidine than guanfacine. Can occur within 24-48 hours of the last dose. Severity ranges from mild hypertension to hypertensive crisis (rare). Always taper. This is the single most important safety counseling point.

Constipation: reported

Reduced GI motility from sympatholytic effects.

Depression: reported at higher doses

Some reports of depressive symptoms. Monitor mood, particularly in patients with pre-existing depression.

Irritability/emotional blunting: reported in some children

Parents may report that the child seems "flat" or less emotionally engaged. Reassess dose and necessity.

See This Medication in Action

These case studies show how clonidine & guanfacine decisions play out in real clinical scenarios:

Neurodevelopmental DisordersThe Pre-Med Who Needs AdderallChild & Adolescent PsychiatryThe Teenager on Too Many MedsNeurodevelopmental DisordersCase 65: Non-Stimulant ADHD Treatment FailureSubstance Use & ComorbidityThe Contractor Who Started with a PrescriptionTrauma & Stressor-Related DisordersThe Veteran Who's "Hearing Things"Side Effect RecognitionAntidepressant Discontinuation SyndromeSleep DisordersThe Nurse Who Just Wants to Sleep

References & Further Reading

This page synthesizes information from standard clinical references. Consult primary sources for all prescribing decisions.

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For learning and board prep — not a prescribing reference. Dosing and safety information change. Always verify against current FDA labeling and your institution’s protocols before prescribing.