Can a healthcare provider prescribe Strattera (atomoxetine) with Cymbalta (duloxetine)?

Can Strattera and Cymbalta Be Prescribed Together?

Yes, a healthcare provider can prescribe Strattera (atomoxetine) with Cymbalta (duloxetine), but this combination requires careful monitoring due to a significant drug-drug interaction that increases atomoxetine exposure and potential adverse effects. 1

Critical Drug Interaction

Duloxetine is a CYP2D6 inhibitor, which significantly alters atomoxetine pharmacokinetics. 1 When these medications are combined:

• Atomoxetine exposure increases to levels similar to those seen in CYP2D6 poor metabolizers (approximately 10-fold higher steady-state concentrations) 2
• Atomoxetine's half-life extends from 5.2 hours to approximately 21.6 hours 2
• Systemic clearance of atomoxetine decreases dramatically (from 0.35 L/h/kg to 0.03 L/h/kg) 2

Prescribing Algorithm When Combining These Medications

Initial Dosing Strategy

• Start atomoxetine at a lower dose than usual (consider 0.5 mg/kg/day initially rather than the standard 1.2 mg/kg/day target) 3, 2
• Titrate atomoxetine more slowly than standard protocols (increase every 2-3 weeks rather than weekly) 3
• Monitor as if the patient is a CYP2D6 poor metabolizer, even if their actual genotype is extensive metabolizer 2

Monitoring Requirements

Cardiovascular monitoring is essential because both medications independently increase blood pressure and pulse, with potentially additive effects: 1, 4

• Measure blood pressure and pulse at baseline, after each dose adjustment, and at least monthly during maintenance 1
• Monitor for sustained clinical hypertension (both drugs can cause this) 1

Hepatic monitoring considerations: 1

• Duloxetine carries risk of hepatic failure (presenting as abdominal pain, hepatomegaly, elevated transaminases) 1
• Discontinue duloxetine immediately if jaundice or clinically significant liver dysfunction develops 1
• While routine transaminase monitoring is not required for duloxetine, maintain high clinical suspicion for hepatic symptoms 1

Adverse Effect Profile to Monitor

Common overlapping adverse effects include: 1, 3

• Nausea and vomiting (particularly prominent with duloxetine initiation) 1, 4
• Decreased appetite and potential weight loss 1
• Dry mouth, headache, dizziness 1, 4
• Somnolence (more common with atomoxetine) 3
• Insomnia 1

Serious adverse effects requiring immediate attention: 1

• Serotonin syndrome risk (duloxetine is an SNRI; atomoxetine affects norepinephrine but combination theoretically increases risk) 1
• Suicidal ideation (both medications carry warnings, particularly in patients under age 24) 1, 3
• Severe skin reactions with duloxetine (erythema multiforme, Stevens-Johnson syndrome) 1
• Behavioral activation, agitation, hypomania, or mania 1

Clinical Scenarios Where This Combination May Be Appropriate

ADHD with comorbid anxiety or depression: 3, 5

• Atomoxetine is particularly useful for ADHD patients with comorbid anxiety or those at risk of substance abuse 3
• Duloxetine has FDA approval for generalized anxiety disorder in children ≥7 years 1
• This combination may address both conditions when monotherapy is insufficient 3, 5

When stimulants are contraindicated or ineffective: 3, 5, 6

• Atomoxetine is the only FDA-approved non-stimulant for ADHD 3, 6
• It has negligible abuse potential and is not a controlled substance 3

Common Pitfalls to Avoid

Do not use standard atomoxetine dosing protocols when combined with duloxetine—this will result in excessive atomoxetine exposure and increased adverse effects 2

Do not combine with MAOIs—this is absolutely contraindicated due to severe serotonin syndrome risk 1, 4

Do not abruptly discontinue either medication—both require slow taper to avoid discontinuation syndrome 1, 4

Do not ignore cardiovascular parameters—the additive effects on blood pressure and pulse can be clinically significant 1, 4

Special Populations

Pregnancy considerations: 1

• Limited data exist for both medications in pregnancy 1
• Atomoxetine shows possible increased risk for spontaneous abortion and preterm birth, though confounding cannot be ruled out 1
• Duloxetine (as an SNRI) may increase risk of persistent pulmonary hypertension of the newborn when used after 20 weeks gestation 1

Breastfeeding: 1

• No published studies exist for atomoxetine during breastfeeding; caution is advised 1
• Duloxetine is present in breast milk at low levels 1

Renal impairment: 4

• Duloxetine requires dose adjustment in renal impairment and should be avoided in severe renal impairment 4