Can I add Wellbutrin (bupropion) to Strattera (atomoxetine) 40mg?

Can Wellbutrin Be Added to Strattera 40mg?

Yes, you can add Wellbutrin (bupropion) to Strattera (atomoxetine) 40mg—this combination is commonly used in clinical practice and appears safe and potentially more effective than monotherapy for treating ADHD and comorbid depression. 1

Rationale for Combination Therapy

The combination of atomoxetine and bupropion targets different neurotransmitter systems, which can provide complementary therapeutic benefits:

• Atomoxetine is a selective norepinephrine reuptake inhibitor that works primarily in the prefrontal cortex, with no appreciable effect on dopamine or serotonin 2
• Bupropion is a norepinephrine and dopamine reuptake inhibitor with no significant serotonin activity 3, 4
• This combination provides enhanced noradrenergic activity plus dopaminergic augmentation without overlapping mechanisms 3

Evidence for Safety and Efficacy

Clinical experience with combining medications that have non-overlapping mechanisms shows favorable outcomes:

• A study of 27 patients combining bupropion with medications having different mechanisms (in that case, serotonin reuptake inhibitors) showed 70% had greater symptomatic improvement with combination therapy than with either agent alone 1
• The combination was used for a mean of 11 months with conservative dosing (bupropion mean 243 mg daily) 1
• Adverse effect risks were similar to monotherapy, with no seizures reported 1

Dosing Recommendations

Start conservatively and titrate based on response:

For Atomoxetine (already at 40mg):

• Current dose of 40 mg daily is the standard starting dose 5
• Can titrate every 7-14 days to 60 mg, then 80 mg if needed 5
• Maximum recommended dose is the lesser of 1.4 mg/kg/day or 100 mg/day 5

For Adding Bupropion:

• Start with bupropion SR 100-150 mg once daily in the morning 5
• Increase by 37.5-75 mg every 3 days as tolerated 5
• Maintenance dose: 100-150 mg twice daily (SR formulation) 5
• Maximum dose: 400 mg/day for SR formulation, 450 mg/day for IR formulation 5, 4
• Give second dose before 3 PM to minimize insomnia risk 5

Critical Safety Considerations

Seizure Risk (Most Important):

• Bupropion lowers the seizure threshold—this is the primary safety concern 5, 4
• Do NOT use in patients with seizure disorders 5
• Do NOT exceed maximum recommended doses 4
• Gradual dose titration is essential to minimize seizure risk 4

Cardiovascular Monitoring:

• Both medications can cause modest increases in heart rate and blood pressure 2
• Monitor blood pressure and heart rate at baseline and during titration 2
• These changes are typically statistically but not clinically significant 2

Drug Interactions:

• Bupropion inhibits CYP2D6, which may affect metabolism of other medications 4
• Atomoxetine is metabolized by CYP2D6, but this interaction is unlikely to be clinically significant since bupropion is being added to stable atomoxetine therapy 2, 4
• Avoid MAOIs—allow at least 14 days between discontinuation of MAOIs and starting bupropion 5

Expected Adverse Effects

Common side effects to monitor:

From Atomoxetine:

• Headache, abdominal pain, decreased appetite, nausea, somnolence 2
• Most adverse events are mild to moderate 2

From Bupropion:

• Activating effects (reduces apathy, increases energy) 5, 3
• Insomnia (give second dose before 3 PM) 5
• Agitation, dry mouth, headache, nausea, tremor 3
• Should NOT be used in agitated patients 5

With Combination:

• Insomnia risk may be higher (22% in combination studies) 1
• Sexual dysfunction (41% in combination studies, though this was with SRIs) 1
• Tremor (11%) 1
• Overall adverse effect profile similar to monotherapy when dosed conservatively 1

Clinical Monitoring Plan

Follow this monitoring schedule:

• Week 1-2: Assess tolerability, particularly insomnia and activation 5
• Week 2-4: Expect initial therapeutic response from bupropion 3
• Week 4-6: Assess full therapeutic effect 3
• Ongoing: Monitor blood pressure, heart rate, weight, and growth (if pediatric patient) 2

Contraindications

Absolute contraindications to this combination:

• Active seizure disorder or history of seizures 5
• Anorexia nervosa or bulimia nervosa (for bupropion) 5
• Abrupt discontinuation of alcohol or benzodiazepines (seizure risk) 5
• Current MAOI use or within 14 days of MAOI discontinuation 5
• Pregnancy (use caution—both medications have limited safety data) 5

Special Populations

Pregnancy and Breastfeeding:

• Both medications should be used with caution 5
• Atomoxetine: No published breastfeeding studies; likely present in milk 5
• Bupropion: Present in breast milk; two case reports of seizures in breastfed infants 5
• Risk-benefit discussion essential if considering during pregnancy or lactation 5