What are the considerations for adding 150mg of Wellbutrin (bupropion) to a patient's current regimen of 60mg of duloxetine?

Adding Bupropion 150mg to Duloxetine 60mg: Clinical Considerations

The combination of duloxetine 60mg and bupropion 150mg is a reasonable and commonly used strategy for treatment-resistant depression, with preliminary evidence suggesting effectiveness and acceptable tolerability, though monitoring for specific adverse effects is essential. 1

Evidence for the Combination

Efficacy Data

• A retrospective study of 10 patients with treatment-resistant major depressive disorder showed significant improvement when duloxetine and bupropion were combined, with 30% achieving remission and 60% showing response (though not full remission) after 8.8 weeks of combination treatment 1
• The mean Clinical Global Impressions-Severity (CGI-S) scores decreased significantly from 4.4 to 2.1 (P <.0001) with combination therapy 1
• However, a more recent double-blind, randomized, placebo-controlled trial in treatment-resistant atypical depression found no significant difference between duloxetine+bupropion versus duloxetine+placebo, with only 26.1% response rate in the combination group versus 21.7% in the duloxetine-alone group 2

Dosing Considerations for This Combination

• The patient's current duloxetine dose of 60mg is the standard therapeutic dose for depression and pain conditions 3, 4
• Starting bupropion at 150mg is appropriate, as the FDA label recommends initiating bupropion at 37.5mg every morning and increasing by 37.5mg every 3 days, with a maximum of 150mg twice daily 5
• In the retrospective study, the mean maximum adjunctive bupropion dose was 175mg (±114.5mg), suggesting 150mg is within the typical range used clinically 1
• Bupropion should be given before 3 p.m. as the second dose to minimize insomnia risk 5

Safety and Monitoring Requirements

Common Adverse Effects to Monitor

The most frequently reported side effects with this combination include: 1

• Nausea (20% of patients)
• Dry mouth (20%)
• Jitteriness/agitation (20%)
• Fatigue/drowsiness (20%)
• Increased blood pressure (10%)
• Increased sweating, insomnia, headache, sexual dysfunction, and weight gain (each 10%)

Critical Safety Considerations

Blood Pressure Monitoring:

• Duloxetine can cause modest hypertension and increases in systolic and diastolic blood pressure 3
• Monitor blood pressure at each follow-up visit, particularly as both medications can affect cardiovascular parameters 3

Seizure Risk:

• Bupropion should not be used in patients with seizure disorders, as it lowers the seizure threshold 5
• The maximum recommended dose of bupropion is 450mg per day to minimize seizure risk 5
• Avoid in patients with eating disorders (bulimia, anorexia) due to increased seizure risk 5

Hepatic and Renal Function:

• For moderate to severe hepatic impairment (Child-Pugh score 7-15), the maximum bupropion dose is 150mg every other day 6
• In renal impairment (GFR <90 mL/min), consider reduced dose and/or frequency for both medications 6
• Duloxetine is not recommended for patients with creatinine clearance <30 mL/min 3

Drug Interaction Concerns

• Duloxetine inhibits CYP2D6, which could theoretically affect metabolism of other medications 7
• Both medications are extensively metabolized in the liver, requiring caution with other hepatically cleared drugs 6

Clinical Pitfalls to Avoid

Timing of Administration:

• Give bupropion's second dose (if splitting to twice daily) before 3 p.m. to prevent insomnia 5
• Taking duloxetine with food can reduce nausea, particularly when initiating or escalating doses 8

Discontinuation Syndrome:

• If either medication needs to be stopped, taper duloxetine gradually over at least 2-4 weeks to minimize withdrawal symptoms 3
• Bupropion can also be tapered over 10-14 days to limit withdrawal symptoms 5

Activation and Agitation:

• Bupropion is activating and may cause rapid improvement in energy level but should not be used in highly agitated patients 5
• Monitor closely for increased agitation or jitteriness, which occurred in 20% of patients in the combination study 1

Alternative Considerations

If the combination proves ineffective after 4-8 weeks at therapeutic doses, consider: 7

• Switching to pregabalin or gabapentin for neuropathic pain components
• Trying alternative antidepressant classes
• Reassessing the diagnosis, particularly for atypical features of depression, which predict poorer response to this combination 2

Important caveat: The presence of more atypical features of depression significantly predicted non-response to the duloxetine-bupropion combination, correctly classifying 73.9% of non-responders 2