Can Rexulti (brexpiprazole) be added to Wellbutrin (bupropion)?

Adding Rexulti (Brexpiprazole) to Wellbutrin (Bupropion)

Yes, Rexulti (brexpiprazole) can be safely added to Wellbutrin (bupropion) without significant drug interactions requiring dose adjustments. According to the FDA drug label, no dosage adjustment of brexpiprazole is required when administered concomitantly with CYP2B6 inhibitors like bupropion 1.

Pharmacological Considerations

Drug Interaction Profile

• Brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6 enzymes
• Bupropion is a CYP2B6 inhibitor
• The FDA label specifically states that no dosage adjustment is needed when brexpiprazole is used with CYP2B6 inhibitors like bupropion 1
• Unlike some drug combinations, this one does not require special dosing considerations

Clinical Applications

Combining these medications may be particularly beneficial for:

1. Major Depressive Disorder (MDD)

   • Brexpiprazole is FDA-approved as an adjunctive therapy with antidepressants for MDD 2
   • Bupropion is an established antidepressant with activating properties 3
   • The combination may help patients with depression who have had an incomplete response to bupropion alone

2. Treatment-Resistant Depression

   • Combination treatments involving different mechanisms of action can be effective for treatment-resistant depression 4
   • Brexpiprazole's serotonin-dopamine activity modulation complements bupropion's norepinephrine-dopamine reuptake inhibition

Dosing Recommendations

Starting and Titration

• For adjunctive treatment of MDD:
  • Start brexpiprazole at 0.5-1 mg once daily
  • Titrate to the recommended dose of 2 mg once daily after 1-2 weeks
  • Maximum dose: 3 mg daily

Monitoring Parameters

• Blood Pressure: Both medications can affect blood pressure; monitor regularly, especially during the first 8 weeks 5
• Mental Status: Watch for changes in mood, behavior, or suicidal thoughts, particularly at initiation or dose changes
• Weight and Metabolic Parameters: Monitor for potential weight gain with brexpiprazole
• Extrapyramidal Symptoms: Although brexpiprazole has lower risk of akathisia than other atypical antipsychotics, still monitor for movement disorders 6

Potential Benefits of This Combination

• Complementary Mechanisms: Brexpiprazole acts as a partial agonist at serotonin 5-HT1A and dopamine D2 receptors and antagonist at 5-HT2A receptors 6, while bupropion affects norepinephrine and dopamine reuptake
• Activation Balance: Bupropion's activating properties may be balanced by brexpiprazole's more moderate receptor activity profile
• Lower Side Effect Burden: Brexpiprazole has a lower intrinsic D2 activity compared to other atypical antipsychotics, suggesting a lower potential for activation-like adverse effects such as akathisia 2

Precautions and Contraindications

• Seizure Risk: Use with caution in patients with a history of seizures as bupropion lowers the seizure threshold 3
• Cardiovascular Effects: Monitor blood pressure as both medications can affect cardiovascular parameters
• Pregnancy: Both medications are contraindicated in pregnancy 3
• Suicidality: Monitor for worsening depression or emergence of suicidal thoughts, particularly in younger patients

Clinical Pearls

• The combination may be particularly useful for patients with depression and comorbid conditions like anxiety or insomnia
• Brexpiprazole has shown efficacy as an adjunctive treatment in patients who have had an inadequate response to antidepressant monotherapy 2
• If a patient is already stable on bupropion, adding brexpiprazole may help address residual symptoms without requiring a medication switch
• Unlike some antipsychotics, brexpiprazole has relatively low incidence of sedation, weight gain, and metabolic abnormalities 6

This combination represents a pharmacologically sound approach for patients with depression who have had an incomplete response to bupropion alone, with minimal drug interaction concerns.