How to safely switch a 14-year-old patient from clonidine (antihypertensive medication) 0.2 mg every night to atomoxetine (non-stimulant medication for attention deficit hyperactivity disorder)?

Switching from Clonidine to Atomoxetine in a 14-Year-Old

Do not abruptly discontinue clonidine 0.2 mg nightly; instead, implement a gradual taper over 3-7 days while simultaneously initiating atomoxetine at a low dose to prevent rebound hypertension and withdrawal symptoms. 1, 2

Critical Safety Concern: Clonidine Withdrawal

Abrupt clonidine discontinuation can cause hypertensive crisis, severe rebound hypertension, tachycardia, agitation, and sympathetic overdrive within 18-36 hours. 2, 3 This is a medical emergency that has been documented in pediatric patients, with symptoms including:

• Severe blood pressure elevation (hypertensive urgency/emergency)
• Elevated serum metanephrines
• Tachycardia and palpitations
• Anxiety, agitation, and tremor
• Headache and diaphoresis 2

The risk is particularly high because this patient is on 0.2 mg nightly, which is a moderate dose. 1

Recommended Transition Protocol

Week 1: Initiate Taper and Start Atomoxetine

Day 1-3:

• Continue clonidine 0.2 mg nightly
• Start atomoxetine 0.5 mg/kg/day (approximately 25-40 mg for average 14-year-old) as a single morning dose 1, 4
• Monitor blood pressure and heart rate daily 1

Day 4-6:

• Reduce clonidine to 0.1 mg nightly (50% reduction)
• Continue atomoxetine at initial dose
• Monitor for withdrawal symptoms: hypertension, tachycardia, anxiety, headache 2, 3

Day 7-9:

• Reduce clonidine to 0.05 mg nightly (further 50% reduction)
• Continue atomoxetine at initial dose
• Continue daily vital sign monitoring 1

Day 10:

• Discontinue clonidine completely
• Continue atomoxetine
• Monitor blood pressure and heart rate for 3-5 days after final clonidine dose 2

Week 2-4: Atomoxetine Titration

After clonidine is fully discontinued:

• Increase atomoxetine to target dose of 1.2 mg/kg/day (maximum 1.4 mg/kg/day or 100 mg, whichever is less) over 2-3 weeks 1, 4
• Increase gradually to minimize gastrointestinal side effects (nausea, vomiting, abdominal pain) 1
• Can be given as single morning dose or split into morning and late afternoon/evening doses if GI side effects occur 1, 4

Pre-Transition Screening Requirements

Before initiating atomoxetine, obtain:

• Detailed cardiac history including family history of sudden death, Wolf-Parkinson-White syndrome, hypertrophic cardiomyopathy, long QT syndrome 1
• Baseline blood pressure and heart rate 1
• Baseline height and weight 1
• Screen for suicidal ideation (FDA black box warning for atomoxetine) 1, 4

An ECG is not routinely required but should be obtained if cardiac risk factors are present. 1

Monitoring During Transition

Daily for first 10 days (during clonidine taper):

• Blood pressure and heart rate to detect rebound hypertension 2, 3
• Symptoms of clonidine withdrawal: severe headache, agitation, tremor, palpitations 2

Weekly for first month:

• Blood pressure and heart rate (atomoxetine can cause mild increases of 1-4 mmHg systolic/diastolic and 1-2 bpm) 1
• Suicidal ideation screening 1, 4
• Gastrointestinal symptoms and appetite 1

Monthly thereafter:

• ADHD symptom monitoring
• Growth parameters (height/weight) 1
• Continued suicidality screening 4

Critical Pitfalls to Avoid

Never abruptly stop clonidine. Even a 12-hour gap between last clonidine dose and starting a replacement medication has caused severe hypertensive crises requiring hospitalization. 3 One study showed that abrupt cessation with beta-blocker replacement 12 hours later resulted in severe blood pressure elevation and intolerable withdrawal symptoms in 100% of patients. 3

Do not use a "cross-taper" approach where you rapidly decrease clonidine while increasing atomoxetine simultaneously over 1-2 days. Atomoxetine takes 6-12 weeks to reach full therapeutic effect for ADHD symptoms, so it provides no protection against clonidine withdrawal. 1, 4

Recognize that atomoxetine has delayed onset. Unlike stimulants which work within hours, atomoxetine requires 6-12 weeks for full ADHD symptom control. 1 The patient and family must understand there will be a gap in ADHD symptom coverage during the transition.

Expected Atomoxetine Effects and Limitations

Atomoxetine has moderate efficacy with an effect size of approximately 0.7 compared to stimulants at 1.0. 1 It is FDA-approved for ADHD in children and adolescents but is considered second-line after stimulants due to smaller effect sizes. 1

Common side effects include:

• Initial somnolence (first 1-2 weeks) 1
• Gastrointestinal symptoms: nausea, vomiting, abdominal pain, decreased appetite 1, 4
• Mild increases in heart rate and blood pressure 1
• Potential for suicidal ideation (rare but requires monitoring per FDA black box warning) 1, 4

Advantages over clonidine:

• "Around-the-clock" ADHD symptom control without sedation 1
• No withdrawal syndrome upon discontinuation 4
• Not a controlled substance 4
• May improve comorbid anxiety symptoms 4

Alternative Consideration

If the primary indication for clonidine was sleep rather than ADHD, consider whether atomoxetine is the appropriate replacement. Clonidine is often used for sleep onset in ADHD patients. 1 If sleep was the primary target, behavioral sleep interventions or melatonin may be more appropriate than atomoxetine, which can occasionally cause insomnia. 4

If clonidine was being used for ADHD symptom control, recognize that stimulant medications (methylphenidate or amphetamines) have superior efficacy compared to atomoxetine. 1 The choice of atomoxetine should be based on specific clinical factors such as comorbid tics, anxiety, substance abuse risk, or stimulant non-response. 1, 4