How the Drug Works

• For ADHD, theoretically has central actions on postsynaptic alpha 2 receptors in the prefrontal cortex

• For hypertension, stimulates alpha 2 adrenergic receptors in the brain stem, reducing sympathetic outflow from the CNS and decreasing peripheral resistance, renal vascular resistance, heart rate, and blood pressure

• An imidazoline, so also interacts at imidazoline receptors

How Long Until It Works

• For ADHD, can take a few weeks to see maximum therapeutic benefits

• Blood pressure may be lowered 30–60 minutes after first dose; greatest reduction seen after 2–4 hours

• May take several weeks to control blood pressure adequately

If It Works

• The goal of treatment of ADHD is reduction of symptoms of inattentiveness, motor hyperactivity, and/or impulsiveness that disrupt social, school, and/or occupational functioning

• Continue treatment until all symptoms are under control or improvement is stable and then continue treatment indefinitely as long as improvement persists

• Reevaluate the need for treatment periodically

• Treatment for ADHD begun in childhood may need to be continued into adolescence and adulthood if continued benefit is documented

• For hypertension, continue treatment indefinitely and check blood pressure regularly

If It Doesn’t Work

• Consider adjusting dose or switching to another agent

• Consider behavioral therapy

• Consider the presence of noncompliance and counsel patient and parents

• Consider evaluation for another diagnosis or for a comorbid condition (e.g., bipolar disorder, substance abuse, medical illness, etc.)

Best Augmenting Combos for Partial Response or Treatment Resistance

• Best to attempt another monotherapy prior to augmenting for ADHD

• Possibly combination with stimulants (with caution as benefits of combination poorly documented and there are some reports of serious adverse events)

• Combinations for ADHD should be for the expert, while monitoring the patient closely, and when other treatment options have failed

• Chlorthalidone, thiazide-type diuretics, and furosemide for hypertension

Tests

• Blood pressure should be checked regularly during treatment

CLONIDINE: SIDE EFFECTS

How Drug Causes Side Effects

• Excessive actions on alpha 2 receptors and/or on imidazoline receptors

Notable Side Effects

✽ Dry mouth

✽ Dizziness, constipation, sedation

• Weakness, fatigue, impotence, loss of libido, insomnia, headache

• Major depression

• Dermatologic reactions (especially with transdermal clonidine)

• Hypotension, occasional syncope

• Tachycardia

• Nervousness, agitation

• Nausea, vomiting

Life-Threatening or Dangerous Side Effects

• Sinus bradycardia, atrioventricular block

• During withdrawal, hypertensive encephalopathy, cerebrovascular accidents, and death (rare)

Weight Gain

• Reported but not expected

Sedation

• Many experience and/or can be significant in amount

• Some patients may not tolerate it

• Can abate with time

What to Do About Side Effects

• Wait

• Take larger dose at bedtime to avoid daytime sedation

• Switch to another medication with better evidence of efficacy

✽ For withdrawal and discontinuation reactions, may need to reinstate clonidine and taper very slowly when stabilized

Best Augmenting Agents for Side Effects

• Dose reduction or switching to another agent may be more effective since most side effects cannot be improved with an augmenting agent

CLONIDINE: DOSING AND USE

Usual Dosage Range

• Extended release for ADHD: 0.1–0.4 mg/day in divided doses

• Immediate release for hypertension: 0.2–0.6 mg/day in divided doses

• Opioid withdrawal: 0.1 mg 3 times daily (can be higher in inpatient setting)

Dosage Forms

• Extended release tablet 0.1 mg, 0.2 mg

• Immediate release tablet 0.1 mg scored, 0.2 mg scored, 0.3 mg scored

• Topical (7 day administration) 0.1 mg/24 hours, 0.2 mg/24 hours, 0.3 mg/24 hours

• Injection 0.1 mg/mL, 0.5 mg/mL

How to Dose

• Oral (for ADHD): initial 0.1 mg at bedtime; can increase by 0.1 mg/day each week with dosing divided and larger dose at bedtime; maximum dose generally 0.4 mg/day in divided doses

• For opioid withdrawal: 0.1 mg 3 times daily; next dose should be withheld if blood pressure falls below 90/60 mm Hg; outpatients should not be given more than a 3-day supply, detoxification can usually be achieved in 4–6 days for short-acting opioids

• Oral (for hypertension): initial 0.1 mg in 2 divided doses, morning and night; can increase by 0.1 mg/day each week; maximum dose generally 2.4 mg/day

• Topical (for hypertension): apply once every 7 days in hairless area; change location with each application

• Injection (for hypertension): initial 30 mcg/hr; maximum 40 mcg/hr; 500 mg/mL must be diluted