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

Adding Wellbutrin (Bupropion) to Rexulti (Brexpiprazole)

Yes, Wellbutrin (bupropion) can be safely added to Rexulti (brexpiprazole) without dosage adjustment, as they do not have clinically significant drug interactions according to FDA labeling. 1

Pharmacological Compatibility

The FDA drug label for brexpiprazole (Rexulti) specifically states that "no dosage adjustment for substrates of CYP2D6, CYP3A4, CYP2B6 (e.g., bupropion), BCRP, or P-gp is required when administered concomitantly with brexpiprazole." 1 This provides clear evidence that these medications can be used together without dosage modifications.

Clinical Applications

This combination may be particularly beneficial in several scenarios:

1. Treatment-resistant depression: When Rexulti alone is not providing adequate symptom relief as an adjunctive treatment for major depressive disorder

2. Depression with low energy: Bupropion is noted to be "activating with possible rapid improvement of energy level" 2, making it a good choice for patients experiencing fatigue or low motivation

3. Depression with cognitive symptoms: Both medications may have positive effects on cognitive function 3

Dosing Considerations

When adding Wellbutrin to Rexulti:

• Starting dose: Begin with 37.5 mg of bupropion every morning, then increase by 37.5 mg every 3 days 2
• Target dose: Up to 150 mg twice daily 2
• Timing: To minimize insomnia risk, administer the second dose before 3 PM 2

Precautions and Monitoring

While these medications can be safely combined, be aware of:

1. Seizure risk: Bupropion should not be used in patients with seizure disorders 2. Monitor closely if the patient has risk factors for seizures.

2. Agitation: Bupropion "should not be used in agitated patients" 2. If the patient is already taking Rexulti for agitation associated with dementia, adding bupropion may be counterproductive.

3. Insomnia: Both medications can potentially cause sleep disturbances. Proper timing of doses and sleep hygiene education are important.

4. Vital signs: Monitor blood pressure and heart rate, as bupropion can have stimulant-like effects.

Evidence of Efficacy

While specific studies on the Rexulti-Wellbutrin combination are limited, there is evidence supporting the use of bupropion with other antidepressants:

• A study examining the combination of duloxetine and bupropion for treatment-resistant depression found significant improvement in Clinical Global Impression scores, with 60% of patients showing response 4

• Bupropion's mechanism as a dopamine and norepinephrine reuptake inhibitor complements Rexulti's action as a serotonin-dopamine activity modulator 5, potentially providing synergistic effects

Clinical Decision Algorithm

1. Assess current symptoms and treatment response:

   • If patient shows partial response to Rexulti but has residual symptoms of fatigue, low motivation, or anhedonia → Add Wellbutrin
   • If patient has significant anxiety, agitation, or insomnia → Consider alternative augmentation strategy

2. Rule out contraindications:

   • History of seizures
   • Current agitation
   • Eating disorders
   • Recent MAO inhibitor use (within 14 days)

3. Initiate and titrate:

   • Start with 37.5 mg in morning
   • Increase gradually to minimize side effects
   • Target 150 mg twice daily if tolerated
   • Administer second dose before 3 PM

4. Monitor for effectiveness and side effects:

   • Follow up within 1-2 weeks of initiation
   • Assess for improvement in depressive symptoms
   • Monitor for emergence of agitation, insomnia, or anxiety

This combination represents a rational pharmacological approach that may be particularly beneficial for patients with depression characterized by low energy, anhedonia, or cognitive symptoms.