Is it safe to combine Wellbutrin (bupropion) and Rexulti (brexpiprazole)?

Combining Wellbutrin (Bupropion) and Rexulti (Brexpiprazole)

The combination of Wellbutrin (bupropion) and Rexulti (brexpiprazole) is safe and does not require dosage adjustments, as FDA labeling specifically states that no dosage adjustment for bupropion is required when administered concomitantly with brexpiprazole. 1

Pharmacological Compatibility

Brexpiprazole (Rexulti) is primarily metabolized through two major pathways:

• CYP3A4 enzyme system
• CYP2D6 enzyme system

According to the FDA drug label for brexpiprazole, bupropion (Wellbutrin) is specifically mentioned as a substrate of CYP2B6, and the label clearly states that "no dosage adjustment for substrates of CYP2B6 (e.g., bupropion) is required when administered concomitantly with brexpiprazole." 1

This is particularly important because:

• Bupropion does not significantly inhibit or induce the CYP3A4 or CYP2D6 pathways that metabolize brexpiprazole
• The two medications work through different mechanisms, which can be complementary in treatment

Clinical Applications

The combination may be particularly useful in:

1. Treatment-resistant depression:

   • Brexpiprazole is FDA-approved as an adjunctive therapy for major depressive disorder 2
   • Bupropion is an established antidepressant with a unique mechanism (dopamine/norepinephrine reuptake inhibitor)

2. Depression with specific symptom profiles:

   • When a patient has depression with low energy, poor concentration, or anhedonia (where bupropion may be helpful)
   • When augmentation is needed for incomplete response to bupropion alone

Monitoring Recommendations

While the combination is pharmacologically compatible, standard monitoring should include:

• Blood pressure and heart rate: Both medications can potentially affect cardiovascular parameters
• Mental status changes: Monitor for changes in mood, behavior, or emergence of suicidal thoughts, especially during the first month of treatment 3
• Weight and metabolic parameters: Brexpiprazole may cause weight gain, while bupropion is often weight-neutral or associated with modest weight loss

Dosing Considerations

When using this combination:

• Start with standard dosing of each medication
• No specific dose adjustments are needed when combining these two medications 1
• If other medications that affect CYP3A4 or CYP2D6 are added to the regimen, dose adjustments of brexpiprazole may be needed

Potential Benefits of Combination

Research on antidepressant combinations suggests that pairing medications with different mechanisms of action may benefit patients who have not responded adequately to monotherapy 4. The combination of bupropion with other psychotropic medications has been studied, showing potential benefits in:

• Addressing a broader spectrum of depressive symptoms
• Potentially reducing sexual side effects that might occur with other antidepressant combinations 5

Important Caveats

• While this specific combination is pharmacologically compatible, always consider the individual patient's complete medication regimen for other potential interactions
• If the patient is taking strong inhibitors of CYP3A4 or CYP2D6, dose adjustments of brexpiprazole (not bupropion) would be necessary 1
• Monitor for any unusual side effects, even though no specific interaction is expected

This combination represents a pharmacologically sound approach for patients who may benefit from both medications' mechanisms of action, with clear FDA guidance supporting their concurrent use without specific dose adjustments.