clonidine ER

General Information

Clonidine extended-release (ER) is a non-stimulant ADHD medication and an alpha-2 adrenergic agonist. It is often used when stimulants are poorly tolerated, when sleep-onset problems are central, or as an adjunct to stimulants for residual hyperactivity/impulsivity.

Compared with guanfacine ER, clonidine ER is often more sedating. That can be useful when insomnia is prominent, but daytime fatigue and dizziness can limit adherence if titration is too rapid.

In serious mental illness, clonidine ER can be attractive when stimulant activation or diversion risk is high, but hypotension, bradycardia, and additive sedation with other CNS depressants are key monitoring targets.

The clonidine ER compare view, evidence feed, and print page can support counseling on titration and tapering.

Clonidine ER is often discontinued due to sedation that is not mitigated by titration speed and dosing timing, or due to rebound symptoms when it is stopped without a taper (rebound hypertension and irritability). When titrated and tapered gradually, it can reduce hyperarousal and support sleep while improving hyperactivity and impulsivity symptoms.

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 can support impulse control and hyperactivity reduction in ADHD.

It does not directly increase dopamine release and has lower misuse risk than stimulants.

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

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

Metabolism and Pharmacokinetics

• Substantial renal elimination (partly unchanged); clearance is reduced in renal impairment and can increase hypotension/sedation risk.
• Half-life is variable and supports twice-daily dosing for ER products; clinical sedation often tracks peak exposure early in treatment.
• Abrupt discontinuation can cause rebound hypertension and agitation; tapering is generally used.

Dosing and Administration

• Typically dosed twice daily; bedtime dosing is common early to reduce daytime sedation.
• Typical initiation is at a low dose with weekly titration as tolerated. Typical total daily dosing is 0.1–0.4 mg/day (product- and age-dependent).
• If sedation limits daytime functioning, slow titration, shift more of the dose to bedtime, or reassess for interacting sedating medications.
• Abrupt discontinuation can trigger rebound hypertension, tachycardia, and irritability; tapering is generally used to reduce these effects.

Monitoring & Labs

• Baseline and periodic blood pressure and heart rate, especially during titration.
• Sedation, dizziness, and orthostasis are monitored; dosing timing and titration speed can be adjusted as needed.
• Interacting medications (antihypertensives, CNS depressants, beta blockers) are reviewed when symptoms change.
• Taper planning in advance helps reduce rebound hypertension and irritability.

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

Adverse Effects

Interactions

• Additive hypotension or sedation can occur with other antihypertensives, CNS depressants, and alcohol.
• Other bradycardia-causing medications (e.g., beta blockers) are often reviewed when symptomatic dizziness or syncope occurs.

Other Useful Information

• Clonidine ER is often used when sleep-onset problems and hyperarousal coexist with ADHD symptoms; sleep goals are commonly tracked in follow-up.
• When daytime fatigue dominates, slower titration or switching to guanfacine ER (often less sedating) is commonly considered rather than adding stimulants solely to counter sedation.
• Baseline blood pressure/heart rate are typically documented and revisited after dose changes.
• In polypharmacy (e.g., multiple sedating agents or antihypertensives), a single documented taper plan across care transitions can help avoid abrupt discontinuation and rebound hypertension.
• When used as add-on therapy with stimulants, stimulant dose reduction is sometimes possible once sleep and hyperarousal improve.

References

1. Clonidine Hydrochloride Extended Release 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)