What are the recommended starting doses and titration schedules for clonidine (for adult hypertension, pediatric attention‑deficit/hyperactivity disorder, and opioid withdrawal)?

Clonidine Dosing Recommendations

Adult Hypertension

For chronic hypertension management, start clonidine at 0.1 mg orally twice daily and titrate by 0.1 mg increments weekly to a maximum of 0.8 mg/day divided into two doses, though clonidine should only be used as a last-line agent after failure of first-line antihypertensives. 1, 2

Chronic Hypertension Dosing

• Starting dose: 0.1 mg orally twice daily (or 0.05–0.1 mg at bedtime to minimize initial sedation) 1, 2
• Titration schedule: Increase by 0.1 mg weekly based on blood pressure response 1
• Maximum dose: 0.8 mg/day, typically divided into two doses 1
• Alternative formulation: Transdermal patch 0.1–0.3 mg applied weekly, which reduces rebound hypertension risk from missed doses 1

Hypertensive Urgencies (Rapid Titration Protocol)

• Initial dose: 0.1–0.2 mg orally 3, 4
• Subsequent doses: 0.1 mg every hour until diastolic blood pressure ≤105 mmHg or total dose reaches 0.5–0.8 mg 5, 3, 4
• Expected response time: Average 1.8–2 hours to achieve blood pressure control 5, 4
• Success rate: 93–97% of patients achieve adequate blood pressure reduction 3, 4
• Target reduction: Decrease mean arterial pressure by ≥20/10 mmHg or achieve diastolic ≤100–105 mmHg 5, 4

Critical Safety Considerations for Hypertension

• Never discontinue abruptly—taper over 2–4 days minimum (7–14 days for long-term use >9 weeks or doses >0.6 mg/day) to prevent hypertensive crisis 1
• Clonidine is reserved as last-line therapy due to significant CNS adverse effects, particularly in older adults 1, 2
• Immediate-release oral tablets require twice-daily dosing and carry higher rebound risk than transdermal patches 1
• For PRN use in adults, withhold dose if systolic blood pressure <100 mmHg or heart rate <60 bpm 6

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Pediatric ADHD

For pediatric ADHD, start clonidine at 0.05–0.1 mg at bedtime and increase by 0.1 mg weekly to a maximum of 0.4 mg/day divided into 2–3 doses, recognizing that stimulants remain first-line therapy. 1, 2

ADHD Dosing Protocol

• Starting dose: 0.05–0.1 mg orally at bedtime 1, 2
• Titration schedule: Increase by 0.1 mg every week 1
• Maximum dose: 0.4 mg/day, typically divided into 2–3 doses 1, 2
• Weight-based dosing: 0.05–0.12 mg/kg/day 7
• Extended-release formulation: Preferred over immediate-release for more stable plasma concentrations and improved adherence 1
• Transdermal patch: Available in 0.1,0.2, and 0.3 mg weekly dosages 2

Combination Therapy with Stimulants

• When combining clonidine with methylphenidate, start with half a tablet (≈0.05 mg) at bedtime and titrate slowly 1
• Maximum dose in combination: 0.3 mg/day (lower than monotherapy maximum) 1
• No routine ECG monitoring required, as serious cardiac events occur in <1% of patients 1, 8
• Monitor for bradycardia (occurs in 17.5% vs 3.4% without clonidine) but this rarely requires discontinuation 8

Pediatric PRN Dosing (Off-Label)

• PRN dose: 0.03–0.05 mg/kg per dose orally every 3–4 hours as needed 6
• Standing dose: 1 mcg/kg orally every 4 hours 6
• Monitor blood pressure and heart rate with each administration 6

ADHD-Specific Considerations

• Clonidine is second-line therapy; stimulants have larger effect sizes and faster onset 2
• Drowsiness is common initially but typically resolves by 6–8 weeks 8
• Asian ADHD guidelines endorse clonidine with maximum doses of 0.2–0.4 mg/day 1
• Clonidine helps control aggression, impulsivity, and stimulant-induced insomnia 1

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Opioid Withdrawal

For opioid withdrawal management, evidence-based dosing protocols are not well-established in the provided guidelines, but pediatric neonatal opioid withdrawal syndrome uses clonidine as a secondary agent with careful titration. 6

Limited Evidence for Opioid Withdrawal

• Clonidine is used as a secondary agent for neonatal opioid withdrawal syndrome 6
• For children ≥12 years, typical starting dose is 0.2 mg/day 6
• No specific adult opioid withdrawal dosing protocols are provided in current high-quality guidelines
• General principles of gradual titration and monitoring for hypotension/bradycardia apply 1, 6

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Special Populations and Universal Precautions

Pregnancy and Breastfeeding

• Clonidine crosses the placental barrier but shows no increased risk of major or minor malformations in studies 1, 2
• Present in human milk with milk-to-plasma ratio of 2 and relative infant dose up to 7.1% 7, 1
• Monitor breastfed infants for drowsiness, hypotonia, apnea, suspected seizures, vomiting, diarrhea, and jitteriness 7, 1, 2
• One case report documented severe infant symptoms (drowsiness, hypotonia, seizures, apnea) with maternal dose of 0.15 mg/day, resolving within 24 hours of breastfeeding cessation 7, 1

Elderly Patients

• Increased risk of orthostatic hypotension, confusion, and falls 1
• Use with extreme caution due to significant CNS effects 1, 6

Critical Withdrawal Prevention

• Patients on concurrent beta-blockers are at greater risk of severe withdrawal reactions; consider discontinuing beta-blockers several days before tapering clonidine 1
• For doses >0.6 mg/day or therapy >9 weeks, extend taper to 7–14 days 1
• Educate patients that abrupt cessation can cause hypertensive crisis, elevated plasma catecholamines, and rare instances of hypertensive encephalopathy, cerebrovascular accidents, and death 1