Can Duloxetine and Bupropion Be Taken Together?
Yes, duloxetine and bupropion can be taken together—this combination is commonly used in clinical practice, particularly for treatment-resistant depression, and has demonstrated effectiveness in multiple studies. 1, 2
Safety Profile of the Combination
The combination has been studied specifically for treatment-resistant major depressive disorder with favorable results:
- In a retrospective study of 10 patients with treatment-resistant depression, 90% responded to the duloxetine-bupropion combination, with 30% achieving full remission. 2
- The combination was generally well tolerated, with most side effects being mild to moderate in severity. 2
Important Drug Interaction Considerations
Both duloxetine and bupropion are CYP2D6 inhibitors, which creates a clinically significant drug interaction that requires monitoring:
- This interaction can increase hydroxybupropion levels, potentially elevating dopamine and increasing the risk of adverse effects including delirium, particularly in elderly patients. 3
- When combined with beta-blockers (metoprolol, propranolol, carvedilol), this CYP2D6 inhibition increases the risk of hemodynamic adverse events including hypotension, bradycardia, and falls. 4
Dosing Recommendations
For bupropion:
- Start at 150 mg once daily, increase to 150 mg twice daily after 3-7 days if tolerated. 1
- Maximum dose should not exceed 300 mg/day when combined with duloxetine to minimize seizure risk. 1
- The second dose should not be taken late in the day to minimize insomnia risk. 5
For duloxetine:
- Can be initiated at 30-60 mg daily and increased to a goal of 60 mg/day. 5
- Duloxetine should be taken daily (not as needed) and has a sufficiently long elimination half-life to permit single daily dosing. 5, 6
- May be administered without regard to food or time of day. 6
Timing of Administration
Duloxetine can be taken once daily at any time of day, while bupropion should be dosed with the second dose earlier in the day (not late afternoon/evening) to prevent insomnia. 5, 6
Critical Monitoring Requirements
Monitor the following parameters when using this combination:
- Baseline and periodic vital signs, particularly blood pressure and heart rate. 1
- Signs of serotonin syndrome (though risk is lower with this combination than with dual serotonergic agents). 1
- Neuropsychiatric effects including suicidal ideation, especially in patients under 24 years old. 5, 1
- Seizure activity, particularly if dose escalation occurs. 1
- In elderly patients, monitor closely for delirium and confusion due to the CYP2D6 interaction. 3
Absolute Contraindications
Do not use this combination in patients with:
- Active seizure disorder or conditions lowering seizure threshold (bupropion lowers seizure threshold). 1
- Concurrent MAO inhibitor use (contraindicated with duloxetine). 5
- Uncontrolled hypertension. 1
- Brain metastases (bupropion contraindication). 1
Common Side Effects to Anticipate
The most frequently reported adverse effects with this combination include:
- Nausea (most common reason for discontinuation). 2
- Dry mouth. 2
- Jitteriness/agitation. 2
- Fatigue/drowsiness. 2
- Increased blood pressure. 2
- Insomnia. 2
- Headache and dizziness. 2
Special Populations
Elderly patients require particular caution:
- Higher risk of delirium due to the CYP2D6 interaction. 3
- May require slower dose titration with smaller increments (37.5 mg decrements for bupropion). 7
Patients with renal impairment:
- Duloxetine should be discontinued and not restarted in patients who develop jaundice or clinically significant liver dysfunction. 5
Discontinuation Protocol
When discontinuing either medication:
- Duloxetine should be tapered over at least 2-4 weeks for patients treated longer than 3 weeks to avoid discontinuation syndrome. 5
- For bupropion SR, reduce from 300 mg daily to 150 mg once daily before complete discontinuation. 7
- Both medications are associated with discontinuation-emergent adverse events, most commonly nausea and dizziness. 6