Yes, taking Rexulti (brexpiprazole) 2mg with Wellbutrin XL (bupropion) 150mg is safe and appropriate.
This combination is explicitly supported by FDA labeling and clinical evidence, with no dosage adjustment required when these medications are used together. The FDA drug label for Rexulti specifically states that no dosage adjustment is needed for substrates of CYP2B6 (which includes bupropion) when administered concomitantly with brexpiprazole 1.
Key Safety Considerations
Drug Interaction Profile
- No pharmacokinetic interaction exists between these medications. Brexpiprazole does not significantly affect bupropion metabolism, and bupropion does not alter brexpiprazole levels 1, 2
- In vitro studies confirm brexpiprazole has only weak inhibitory effects on CYP2B6 (the enzyme that metabolizes bupropion), with an IC50 of 8.19 μmol/L—far above clinically relevant concentrations 2
Clinical Context
This combination is commonly used in two scenarios:
For Major Depressive Disorder (MDD):
- Rexulti is FDA-approved as an adjunctive treatment to antidepressants for MDD 1
- Clinical trials specifically included patients taking various antidepressants, including bupropion 3, 4
- Studies demonstrate that brexpiprazole 2mg effectively augments antidepressant therapy with a favorable tolerability profile 4, 5
For patients switching from other medications:
- Case series data show patients who had insufficient outcomes with bupropion alone may benefit from adding or switching to brexpiprazole 3
Important Monitoring Points
Seizure Risk
- Bupropion lowers seizure threshold, particularly at doses above 300mg/day 6
- Your 150mg dose is well below the concerning threshold
- Bupropion is contraindicated in patients with seizure disorders, eating disorders (bulimia/anorexia), or abrupt alcohol/benzodiazepine withdrawal 6
- Brexpiprazole does not increase seizure risk 7
Neuropsychiatric Monitoring
- Both medications carry warnings about monitoring for worsening depression or suicidal ideation, particularly in patients under 24 years old 1
- Watch for new or worsening mood changes, especially in the first few weeks of treatment
Metabolic Effects
- Brexpiprazole can cause weight gain, increased blood sugar, and lipid abnormalities 1
- Bupropion is generally weight-neutral or associated with modest weight loss 8
- Monitor weight, blood glucose, and lipid panels periodically
Common Side Effects to Expect
From Rexulti: Akathisia (restlessness), weight gain, drowsiness, headache 1
From Wellbutrin: Insomnia, dry mouth, headache, nausea, increased blood pressure 6, 8
Practical Recommendations
- Take Wellbutrin XL in the morning to minimize insomnia risk 8
- Rexulti can be taken once daily with or without food, at any time of day 1
- No dose adjustments needed for either medication when used together
- Avoid overheating and dehydration while on Rexulti 1
- Do not stop either medication abruptly without consulting your prescriber
When to Seek Immediate Medical Attention
Contact your healthcare provider immediately if you experience:
- New or worsening suicidal thoughts
- Seizures
- High fever with muscle stiffness (neuroleptic malignant syndrome)
- Uncontrolled movements of face, tongue, or body
- Severe agitation or confusion
- Signs of high blood sugar (excessive thirst, urination, fruity breath)
This combination is well-established in clinical practice and supported by both FDA labeling and clinical evidence, making it a safe and appropriate treatment regimen when properly monitored.