clonidine

General Information

Clonidine is a centrally acting alpha-2 adrenergic agonist approved for hypertension (label). In psychiatric practice it is sometimes used off-label as an adjunct when reducing sympathetic activation is part of the treatment goal (e.g., hyperarousal, anxiety-related insomnia, withdrawal-related symptoms).

Clonidine is not a primary long-term treatment for anxiety disorders; it is typically layered onto first-line approaches (psychotherapy and/or SSRIs/SNRIs) for targeted symptoms.

The main safety limits are hypotension, bradycardia, dizziness, and sedation. Monitoring is typically more important than for many other short-term anxiety adjuncts because clonidine affects cardiovascular vitals (label).

Abrupt discontinuation can cause rebound hypertension and agitation; a taper plan is commonly used to reduce risk, especially after regular use (label).

The clonidine compare view, clonidine evidence feed, and clonidine print page can support counseling about monitoring and safer alternatives.

Clonidine’s value in psychiatric settings is often symptom-targeted (sleep onset, hyperarousal, withdrawal-related autonomic symptoms). Its risks are also symptom-driven: orthostasis, sedation, and rebound hypertension are common reasons for discontinuation. Planned titration, vital sign monitoring, and taper planning improve safety.

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, lowering blood pressure and heart rate (label).

Reduced sympathetic activation can also reduce physical arousal symptoms (e.g., palpitations, sweating) that overlap anxiety presentations.

Sedation and orthostasis reflect alpha-2 effects; dosing timing and titration speed are practical levers to improve tolerability.

• Alpha-2 adrenergic agonist (primary).
• Not a controlled substance; no direct stimulant-release mechanism.

Metabolism and Pharmacokinetics

• Following oral administration, ~40–60% of absorbed dose is recovered in urine as unchanged drug in 24 hours; ~50% is metabolized in the liver (label).
• Elimination half-life ranges from 12–16 hours and can increase up to ~41 hours in severe renal impairment (label).
• Prolonged half-life in renal impairment can increase hypotension and sedation risk; conservative dosing and follow-up are common (label/class).

Dosing and Administration

• Hypertension labeling commonly starts at 0.1 mg twice daily (morning and bedtime) (label).
• Dose increases of 0.1 mg/day may be made at weekly intervals as needed; taking a larger portion of the daily dose at bedtime can reduce transient dry mouth and drowsiness (label).
• For off-label psychiatric use, clinicians often start lower and individualize dosing to symptoms and vitals; careful titration is used to reduce orthostasis and sedation (clinical practice pattern).
• If discontinuing after regular use, tapering is commonly used to reduce rebound hypertension and agitation (label).

Monitoring & Labs

• Baseline and periodic blood pressure and heart rate, especially during titration or dose changes.
• Orthostasis, dizziness, and sedation; adjust dosing timing and review interacting medications if symptoms emerge.
• Renal impairment and medication adherence; missed doses can trigger rebound hypertension in some patients.
• Discontinuation plan documented in advance to reduce rebound hypertension and agitation risk.

Sources: FDA/DailyMed label; ADHD guideline context for alpha-2 agonists.

Adverse Effects

Interactions

• Additive hypotension or bradycardia can occur with other antihypertensives and some rate-controlling agents; symptomatic dizziness or syncope prompts review of the full regimen.
• Additive sedation can occur with alcohol and other CNS depressants, including sedating antipsychotics and hypnotics.
• When combined with beta blockers, discontinuation planning matters because abrupt clonidine cessation can increase rebound hypertension risk.

Other Useful Information

• Clonidine extended-release (ER) is a separate product used for ADHD in some settings; immediate-release clonidine is not interchangeable with ER formulations (see clonidine ER) (label/guidelines).
• When insomnia or hyperarousal is a prominent target, comparing clonidine to alternatives that do not lower blood pressure can clarify tradeoffs (e.g., hydroxyzine, trazodone, DORAs).
• For persistent anxiety disorders, the primary treatment is usually therapy and/or an SSRI/SNRI; clonidine is typically an adjunct for selected symptoms rather than a stand-alone long-term plan.

References

1. Clonidine hydrochloride 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)