What are the guidelines for using Wellbutrin (bupropion) with Strattera (atomoxetine) in patients?

Combining Wellbutrin (Bupropion) with Strattera (Atomoxetine)

The combination of bupropion and atomoxetine can be used together safely with appropriate monitoring, though no specific guidelines directly address this combination—both medications are effective for ADHD and depression respectively, with atomoxetine monotherapy showing efficacy even when depressive symptoms are present. 1

Mechanism and Rationale

• Bupropion is a dopamine-norepinephrine reuptake inhibitor with no appreciable serotonergic activity, making it unique among antidepressants 2, 3
• Atomoxetine is a selective norepinephrine reuptake inhibitor used for ADHD treatment 4
• Both medications work through noradrenergic pathways but have distinct mechanisms, which theoretically allows for combination use without direct pharmacodynamic conflicts 2, 1

Safety Considerations When Combining

Cardiovascular Monitoring

• Monitor blood pressure and heart rate closely when using these medications together, as both can increase these parameters 4
• Bupropion can cause elevated heart rate and blood pressure 4
• Atomoxetine combination therapy (studied with fluoxetine) showed greater increases in blood pressure and pulse compared to monotherapy 1
• Contraindicated in patients with uncontrolled hypertension 4

Seizure Risk

• Bupropion carries a dose-dependent seizure risk that must be carefully managed 4, 2
• Maximum dose should not exceed 450 mg/day for immediate-release or 400 mg/day for sustained-release formulations 2
• Contraindicated in patients with seizure disorders, brain metastases, or stroke history 4
• The seizure incidence is less than 0.1% when proper dosing and screening are followed 5, 6

Neuropsychiatric Effects

• Monitor for development or worsening of depression, suicidal ideation, anxiety, or agitation with both medications 4
• Bupropion carries a black box warning for suicidal behavior/ideation in patients younger than 24 years with depression 4
• Agitation/excitement is the most common cause for discontinuation (9.1% with bupropion) 6

Dosing Approach

Bupropion Initiation

• Start with 100-150 mg once daily (SR formulation) or 150 mg once daily (XL formulation) 4
• Titrate gradually: for SR, increase to 100-150 mg twice daily; for XL, increase to 150-300 mg daily 4
• Maximum dose: 450 mg per day 4, 2
• Give second dose before 3 p.m. to minimize insomnia risk 4

Atomoxetine Initiation

• Start with 40 mg once daily 4
• Titrate every 7-14 days to 60 mg, then 80 mg as tolerated 4
• Maximum dose: 1.4 mg/kg/day or 100 mg/day, whichever is less 4

Common Side Effects to Anticipate

Bupropion-Specific

• Insomnia (most common), dry mouth, headache, nausea, anxiety 4, 5, 3
• These are generally transient and resolve within 4-5 days without intervention 2, 5
• Insomnia and dry mouth occur significantly more frequently than placebo 5

Atomoxetine-Specific

• Possible increased risk for spontaneous abortion (though confounding by indication cannot be ruled out) 4
• Generally well tolerated with no major congenital malformations reported 4

Overlapping Effects

• Both medications can cause increased blood pressure, heart rate, insomnia, and anxiety 4, 1

Clinical Evidence for Combination

• Atomoxetine combined with fluoxetine was well tolerated in pediatric ADHD patients with comorbid depression/anxiety, with marked reductions in ADHD, depressive, and anxiety symptoms 1
• While this study used fluoxetine rather than bupropion, it demonstrates that atomoxetine can be safely combined with antidepressants when appropriately monitored 1
• Atomoxetine monotherapy showed efficacy for ADHD even when depressive symptoms were present, suggesting combination therapy may not always be necessary 1

Key Contraindications

• Do not use bupropion within 14 days of MAOI use 4
• Avoid in patients with seizure disorders, eating disorders (bulimia/anorexia), or abrupt discontinuation of alcohol/benzodiazepines 4
• Contraindicated in pregnancy and breastfeeding (both medications) 4
• Caution advised for atomoxetine during breastfeeding due to lack of published data 4

Monitoring Protocol

• Baseline and periodic blood pressure and heart rate measurements 4
• Screen for seizure risk factors before initiating bupropion 4, 5
• Monitor for neuropsychiatric symptoms including depression, suicidal ideation, and agitation 4
• Assess therapeutic response at 4-8 weeks, as full efficacy requires this duration 4, 2