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

Can You Add Strattera to Wellbutrin?

Yes, Strattera (atomoxetine) and Wellbutrin (bupropion) can be safely combined, though you must start atomoxetine at a lower dose and monitor closely for adverse effects in the first 24-48 hours. 1, 2

Dosing Strategy for Combination Therapy

When adding Strattera to existing Wellbutrin therapy:

• Start atomoxetine at 40 mg daily or less if bupropion is already being taken 1
• Titrate atomoxetine every 7-14 days to 60 mg, then 80 mg daily as tolerated 1, 2
• Maximum atomoxetine dose is the lesser of 1.4 mg/kg/day or 100 mg/day 1, 2
• Bupropion dosing remains 100-150 mg twice daily (SR formulation) or 150-300 mg once daily (XL formulation), with a maximum of 450 mg per day 1, 2

Critical Monitoring Requirements

Watch for early warning signs within the first 24-48 hours after initiation or any dose changes: 1

• Agitation, tremor, or insomnia 1
• Mental status changes (confusion, restlessness) 1
• Neuromuscular hyperactivity (tremors, clonus, hyperreflexia) 1
• Autonomic symptoms (hypertension, tachycardia, diaphoresis) 1
• Mood destabilization (irritability, hostility, impulsivity, mania) 3

Cardiovascular Monitoring

Both medications affect cardiovascular parameters: 2

• Monitor blood pressure and heart rate at baseline and after dose changes 2
• Both drugs can cause statistically significant (though not always clinically significant) increases in heart rate and blood pressure 2, 4
• Use caution in patients with pre-existing cardiovascular conditions 2

Seizure Risk Considerations

Bupropion lowers the seizure threshold in a dose-dependent manner: 2, 5

• Bupropion is absolutely contraindicated in patients with seizure disorders, stroke history, or brain metastases 2
• The seizure risk increases at doses above 450 mg/day 2, 5
• Combining with atomoxetine does not appear to further increase seizure risk, but maintain vigilance 2

Neuropsychiatric Monitoring

Both medications carry warnings about neuropsychiatric effects: 2

• Atomoxetine has a black-box warning for suicidal ideation, particularly in the first months of treatment or after dose changes 4
• Monitor for agitation, irritability, suicidal thinking, self-harming behavior, or unusual behavioral changes 2
• Recent evidence suggests these risks may be lower than previously thought, but monitoring remains essential 2

Pharmacological Rationale

The combination targets different neurotransmitter pathways: 2

• Atomoxetine selectively inhibits norepinephrine reuptake, primarily affecting prefrontal cortex function 2, 4
• Bupropion acts as a noradrenergic/dopaminergic antidepressant through different mechanisms 5
• This dual mechanism can provide additive therapeutic effects for ADHD symptoms 2, 6

Evidence for Combination Use

While guidelines support this combination, the evidence base has limitations: 2

• The American College of Obstetricians and Gynecologists and other medical guidelines indicate this combination can be used safely with careful monitoring 2
• Case reports demonstrate effective combination use for extending symptom relief duration or addressing a wider symptom range 6
• However, there is limited large-scale research specifically on this combination, necessitating cautious clinical monitoring 2, 6

Common Pitfalls to Avoid

• Do not start atomoxetine at full dose (80-100 mg) when bupropion is already on board—this increases risk of adverse effects 1
• Do not ignore early warning signs in the first 48 hours—most serious adverse effects emerge during this window 1
• Do not exceed bupropion 450 mg/day—seizure risk increases substantially above this threshold 2, 5
• Do not combine if patient has seizure disorder—bupropion is absolutely contraindicated 2