Is it safe to combine Lexapro (escitalopram) and Strattera (atomoxetine)?

Safety of Combining Lexapro (Escitalopram) and Strattera (Atomoxetine)

The combination of Lexapro (escitalopram) and Strattera (atomoxetine) can be used together with caution, but requires careful monitoring for potential serotonergic effects and cardiovascular side effects.

Pharmacological Considerations

Mechanism of Action

• Lexapro (escitalopram): Selective serotonin reuptake inhibitor (SSRI) that inhibits presynaptic serotonin transport 1
• Strattera (atomoxetine): Selective norepinephrine reuptake inhibitor (SNRI) with high affinity and selectivity for norepinephrine transporters 2

Potential Interactions

1. Serotonergic Effects

   • While atomoxetine primarily affects norepinephrine, caution is warranted as combining two or more non-MAOI serotonergic drugs (including SSRIs) may increase risk of serotonin syndrome 3
   • Guidelines recommend monitoring for symptoms in the first 24-48 hours after combining serotonergic medications or changing doses 3

2. Cardiovascular Effects

   • Both medications can affect cardiovascular parameters:
     • Atomoxetine can cause statistically (though not usually clinically) significant increases in heart rate and blood pressure 2
     • Escitalopram has been associated with QT prolongation at higher doses 3

3. Metabolic Considerations

   • Atomoxetine is metabolized by CYP2D6 2
   • Escitalopram has minimal effect on CYP450 isoenzymes compared to other SSRIs, giving it a lower propensity for drug interactions 3

Monitoring Recommendations

When combining these medications:

1. Initial Phase (First Month)

   • Monitor for signs of serotonin syndrome within first 24-48 hours after starting combination or changing doses 3:
     • Mental status changes (confusion, agitation)
     • Neuromuscular hyperactivity (tremors, clonus, hyperreflexia)
     • Autonomic hyperactivity (hypertension, tachycardia, diaphoresis)

2. Regular Monitoring

   • Check blood pressure and heart rate at baseline and periodically 4
   • Monitor for hepatic function, as atomoxetine has rarely been associated with liver injury 2
   • Watch for psychiatric symptoms, as both medications can affect mood 4

3. Dosing Considerations

   • Start with lower doses when initiating the second medication
   • For atomoxetine, typical target dose is 1.2 mg/kg/day (maximum 1.4 mg/kg/day or 100 mg daily) 4
   • Dose adjustments may be needed for patients who are poor CYP2D6 metabolizers (approximately 7% of population) 4

Special Considerations

• Poor CYP2D6 Metabolizers: May require lower atomoxetine doses due to slower clearance 2
• Hepatic Impairment: Atomoxetine doses should be reduced to 50% in moderate impairment and 25% in severe impairment 4
• Bleeding Risk: SSRIs can increase risk of abnormal bleeding, especially when combined with NSAIDs or aspirin 3

Common Side Effects to Monitor

• Gastrointestinal: Nausea, abdominal pain, decreased appetite (common with both medications) 2, 1
• Neurological: Headache, somnolence (atomoxetine), insomnia (can occur with both) 2
• Cardiovascular: Changes in blood pressure or heart rate 5

Conclusion

While the combination of Lexapro and Strattera is not explicitly contraindicated, careful monitoring is essential, particularly during initiation and dose adjustments. The combination appears to have a manageable risk profile when used with appropriate caution and monitoring, especially given that escitalopram has fewer drug interactions compared to other SSRIs 3.