Drug Interactions Between Clonidine, Strattera (Atomoxetine), and Dextromethorphan
When combining clonidine with Strattera (atomoxetine), use extreme caution with cardiovascular monitoring and slow titration; dextromethorphan should be used cautiously due to serotonin syndrome risk when combined with other serotonergic agents, though it has been safely combined with clonidine in specific clinical contexts.
Clonidine and Strattera (Atomoxetine) Combination
Cardiovascular Risks and Monitoring Requirements
Obtain baseline cardiovascular assessment before initiating this combination, including detailed personal and family cardiac history (sudden death, repeated fainting, arrhythmias), baseline heart rate and blood pressure, and consider ECG if any cardiac risk factors exist 1, 2.
Clonidine can cause bradycardia, hypotension, and AV conduction abnormalities, with documented cases of complete AV block when combined with other cardiac-active medications 1, 2.
Exercise extreme caution in patients with AV conduction disease, as the combination significantly increases risk of complete heart block 1.
Dosing and Titration Strategy
Start clonidine at the absolute minimum dose of 0.05 mg at bedtime, with slow titration not exceeding 0.3 mg/day 1, 2.
When combining with atomoxetine, start atomoxetine at 40 mg daily and adjust only every 7-14 days, with maximum dosing of 1.4 mg/kg/day or 100 mg/day 1, 2.
Titrate clonidine by 0.1 mg BID-TID intervals to maximum 0.4 mg daily, though lower maximums are safer with concurrent atomoxetine 1.
Clinical Experience and Safety Data
This combination is most commonly used in pediatric patients for ADHD management, particularly when tics are present 1, 3, 4.
One case report documented successful concomitant use of atomoxetine with other medications including clonidine in a 10-year-old with ADHD, bipolar disorder, and Tourette syndrome, though polypharmacy requires contingent management strategies 3.
Be aware of emergent dyskinesias when combining atomoxetine with other medications; one case report documented a 9-year-old taking clonidine and dextroamphetamine who developed psychosis, abnormal involuntary movements, and insomnia when atomoxetine was added 5.
Special Monitoring Considerations
Baseline and periodic heart rate and blood pressure measurements are necessary, along with ECG monitoring if any cardiac risk factors are present 1, 2.
Patients with hepatic insufficiency require lower doses of atomoxetine and more frequent monitoring 1, 2.
Be alert for rebound hypertension if clonidine is abruptly discontinued 2.
Dextromethorphan Interactions
Serotonin Syndrome Risk
Dextromethorphan is a serotonergic medication that can trigger serotonin syndrome when combined with other serotonergic drugs, including SNRIs like atomoxetine 6.
Serotonin syndrome symptoms can arise within 24 to 48 hours after combining medications and are characterized by mental status changes (confusion, agitation, anxiety), neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity), and autonomic hyperactivity (hypertension, tachycardia, arrhythmias, tachypnea, diaphoresis, shivering, vomiting, diarrhea) 6.
Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness, which can lead to fatalities 6.
Cautious Use Guidelines
When combining two or more non-MAOI serotonergic drugs (including atomoxetine and dextromethorphan), start the second drug at a low dose, increase slowly, and monitor for symptoms, especially in the first 24 to 48 hours after dosage changes 6.
The combination dextromethorphan/quinidine should be used with caution due to limited efficacy in certain populations while potentially increasing the risk of falls and drug-drug interactions 6.
Dextromethorphan and Clonidine Combination
Dextromethorphan has been safely combined with clonidine in clinical trials for opioid withdrawal, with one study showing that combination therapy resulted in milder withdrawal symptoms compared to clonidine alone 7.
This suggests that the dextromethorphan-clonidine combination itself does not pose major safety concerns, though this was studied in a different clinical context 7.
Clinical Pitfalls to Avoid
Do not combine all three medications (clonidine, atomoxetine, and dextromethorphan) without careful consideration of cumulative CNS effects and serotonin syndrome risk.
Avoid abrupt discontinuation of clonidine due to rebound hypertension risk 2.
Do not ignore cardiovascular symptoms (bradycardia, hypotension, syncope) in patients on clonidine-atomoxetine combinations 1, 2.
Be vigilant for dyskinesias or movement disorders when atomoxetine is combined with other psychoactive medications, as these may not respond to diphenhydramine and require discontinuation of the offending agent 5.
Monitor for drug-drug interactions involving CYP2D6, as atomoxetine is metabolized by this enzyme and poor metabolizer status can lead to elevated drug levels and toxicity 5.