Can Strattera (atomoxetine) and Wellbutrin (bupropion) be used together?

Using Strattera (Atomoxetine) and Wellbutrin (Bupropion) Together

The combination of Strattera (atomoxetine) and Wellbutrin (bupropion) can be used together with careful monitoring, though this combination is not explicitly endorsed in current guidelines and requires close attention to potential side effects. 1

Pharmacological Considerations

• Mechanism of Action:

  • Atomoxetine: Selective norepinephrine reuptake inhibitor
  • Bupropion: Dopamine and norepinephrine reuptake inhibitor

• Potential Benefits:

  • The combination may provide broader neurotransmitter coverage (affecting norepinephrine, dopamine, and to a lesser extent, serotonin systems)
  • May be beneficial for patients with partial response to either medication alone

Safety Considerations

Cardiovascular Monitoring

• Both medications can increase blood pressure and heart rate
• Regular monitoring of cardiovascular parameters is essential at each visit 1
• Use with extreme caution or avoid in patients with cardiovascular disease

Neuropsychiatric Effects

• Monitor for:
  • Increased anxiety or agitation
  • Mood changes
  • Suicidal ideation (particularly during initial titration)
  • Seizure risk (bupropion lowers seizure threshold)

Drug Interactions

• Both medications are metabolized through the CYP2D6 pathway
• Bupropion is a CYP2D6 inhibitor and may increase atomoxetine levels
• Consider starting atomoxetine at 50% of the normal dose when adding to existing bupropion therapy 1
• Increase doses slowly with at least 1-2 weeks between adjustments

Dosing Recommendations

• Atomoxetine:

  • Starting dose: 40 mg daily (adults)
  • Titration: Adjust every 7-14 days to 60 mg then 80 mg daily
  • Maximum dose: 1.4 mg/kg/day or 100 mg daily (whichever is lower) 2

• Bupropion:

  • SR formulation: Start at 100-150 mg daily, maintenance 100-150 mg twice daily
  • XL formulation: Start at 150 mg daily, maintenance 150-300 mg daily
  • Maximum dose: 450 mg per day 2

Monitoring Protocol

• Initial Phase (first 4 weeks):

  • Weekly monitoring of blood pressure, heart rate
  • Assessment for anxiety, agitation, insomnia
  • Evaluation of mood and suicidal ideation

• Maintenance Phase:

  • Monthly monitoring of vital signs
  • Regular assessment of mental health status
  • Periodic liver function tests

Special Populations

Pregnancy

• Both medications have limited data in pregnancy
• Atomoxetine does not appear to be associated with major congenital malformations 2
• Bupropion has been associated with a small absolute increase in risk of cardiovascular malformations in some studies, though data are conflicting 2

Breastfeeding

• Limited data for both medications during breastfeeding
• Atomoxetine: Likely present in breast milk; effects on nursing infants unknown 2, 1
• Bupropion: Present in breast milk at low levels; two case reports of seizures in breastfed infants 2

Potential Adverse Effects

• Common side effects:

  • Headache
  • Insomnia
  • Dry mouth
  • Nausea
  • Decreased appetite
  • Increased blood pressure and heart rate

• Rare but serious concerns:

  • Serotonin syndrome (although rare with this combination) 3
  • Seizures (particularly with bupropion at higher doses)
  • Liver dysfunction
  • Suicidal ideation (particularly in younger patients)

Practical Approach

1. Start with one medication and stabilize before adding the second
2. Begin with lower doses of both medications when using in combination
3. Titrate doses slowly with careful monitoring
4. Adjust doses based on efficacy and tolerability
5. Consider discontinuation of one or both medications if serious side effects occur

While this combination is not explicitly recommended in guidelines, clinical experience suggests it may be beneficial for patients with inadequate response to monotherapy, particularly those with both ADHD and depression or anxiety disorders.