Clonidine Extended Release for ADHD and Hypertension
Clonidine extended release is recommended at a starting dose of 0.1 mg at bedtime, which can be increased to twice-daily administration with careful uptitration, not exceeding 0.4 mg/day for both ADHD and hypertension management. 1, 2
Dosage and Administration
For ADHD:
- Starting dose: 0.1 mg tablet at bedtime
- Titration: Can be increased to twice-daily administration
- Maximum dose: 0.4 mg/day (doses higher than this are not recommended)
- Extended-release formulation: Available in 0.1 and 0.2 mg tablets
- Transdermal option: Also available as patches (0.1,0.2, and 0.3 mg) 1
For Hypertension:
- Initial dose: 0.1 mg tablet twice daily (morning and bedtime)
- Titration: Further increments of 0.1 mg per day at weekly intervals until desired response
- Maintenance dose: Typically ranges from 0.2 mg to 0.6 mg per day in divided doses
- Maximum effective dose: 2.4 mg daily (rarely employed) 2
- Elderly patients: May benefit from a lower initial dose
- Renal impairment: Lower initial dose recommended with careful monitoring 2
Efficacy
ADHD Treatment:
- Clonidine extended-release has been FDA-approved for ADHD treatment in children and adolescents (6-17 years) 3, 4
- Efficacy has been demonstrated in multiple clinical trials as both:
- Symptomatic improvement typically begins after 2 weeks of treatment 4
- Effect size is generally in the medium range, smaller than stimulants 1
- Treatment effects typically take 2-4 weeks to be observed (compared to 6-12 weeks for atomoxetine) 1
Hypertension Management:
- Works through alpha-2 agonism, reducing peripheral vascular resistance and lowering blood pressure 1, 2
- Therapeutic doses commonly range from 0.2 mg to 0.6 mg daily in divided doses 2
Mechanism of Action
Clonidine works through:
- Agonism at alpha-2 adrenergic receptors throughout the brain
- In the brain stem: Reduces peripheral vascular resistance (lowers blood pressure)
- In the prefrontal cortex: Enhances noradrenergic neurotransmission, strengthening the regulatory role of the prefrontal cortex for attention, thought, and working memory 1
- Metabolized primarily via CYP2D6 and excreted renally and hepatically in equal shares 1
Adverse Effects
Common side effects include:
- Somnolence/sedation (most common)
- Fatigue
- Irritability
- Insomnia and nightmares
- Dry mouth
- Bradycardia
- Hypotension 1, 3, 4
Warnings include:
- Hypotension/bradycardia
- Somnolence/sedation
- Discontinuation effects
- Allergic reactions
- Cardiac conduction abnormalities 1
- Rare but serious cardiac side effects have been reported historically, particularly in cases with other risk factors 3, 6
Special Considerations
- Pregnancy: Limited data suggests clonidine is likely not associated with adverse pregnancy outcomes, but should be used with caution 1
- Breastfeeding: Clonidine is found in human milk (M:P ratio reported as 2 with RID up to 7.1%). Monitor breastfed infants for drowsiness and hypotonia 1
- Prison settings: May be preferred over stimulants due to lack of abuse potential 7
- Renal impairment: Lower initial dose with careful monitoring is recommended 2
- Administration timing: Taking the larger portion of the daily dose at bedtime may minimize transient effects of dry mouth and drowsiness 2
Comparative Efficacy
- Clonidine is generally considered a second-line treatment for ADHD after stimulants due to smaller effect size 1
- Compared to guanfacine (another alpha-2 agonist):
- Clonidine is approximately ten times more potent
- Clonidine has less specificity for alpha-2A receptors
- Clonidine may have more sedative effects 1
Clinical Pearls
- Monitor blood pressure, heart rate, and cardiac function during treatment
- Avoid abrupt discontinuation to prevent rebound hypertension
- Consider evening dosing to minimize daytime sedation
- May be particularly helpful for ADHD with associated aggression or conduct disorder features 7
- Can be beneficial for patients with comorbid anxiety or PTSD symptoms 7