Is it safe to prescribe Wellbutrin (bupropion) and Prozac (fluoxetine) together?

Prescribing Wellbutrin and Prozac Together

Yes, you can safely prescribe Wellbutrin (bupropion) and Prozac (fluoxetine) together, but you must monitor for drug interactions and potential increased risk of adverse effects.

Pharmacological Considerations

Bupropion and fluoxetine work through different mechanisms, making them potentially complementary:

• Fluoxetine (Prozac): Selective serotonin reuptake inhibitor (SSRI) 1
• Bupropion (Wellbutrin): Activating antidepressant that affects dopamine and norepinephrine 1

Drug Interaction Concerns

The most important interaction to be aware of:

• Fluoxetine inhibits CYP2D6, which can increase bupropion concentrations 2
• Bupropion also inhibits CYP2D6, potentially increasing fluoxetine levels 2

Dosing Recommendations

Start with conservative dosing:

• Fluoxetine: Begin with 10mg every other morning, can increase to 20mg daily 1
• Bupropion: Start at 37.5mg every morning, increase by 37.5mg every 3 days as tolerated, to maximum 150mg twice daily 1

Monitoring Protocol

1. Initial phase: Assess patient within 1-2 weeks of starting combination therapy 1
2. Follow-up: Monthly for first 3 months, then quarterly if stable
3. Monitor for:
   • Suicidal thoughts (especially in first 1-2 months) 1
   • Sexual dysfunction (lower with bupropion than with fluoxetine alone) 1
   • Insomnia, agitation, or seizures (bupropion lowers seizure threshold) 1
   • Drug interactions with other medications 2

Advantages of This Combination

1. Complementary mechanisms: May provide better efficacy than monotherapy 3, 4
2. Sexual dysfunction: Bupropion may counteract the sexual side effects of fluoxetine 5
3. Energy levels: Bupropion's activating properties may offset potential SSRI-induced fatigue 1, 6

Contraindications and Cautions

Do not use this combination in patients with:

• Seizure disorders 1
• Eating disorders 1
• Recent head trauma 1
• Patients taking MAO inhibitors 2

Evidence for Efficacy

Research supports the combination of bupropion with SSRIs:

• 70% of patients showed greater improvement with combined SSRI and bupropion than with either agent alone 3
• Combination therapy from treatment initiation may double remission rates compared to monotherapy 7

Common Pitfalls to Avoid

1. Inadequate monitoring: Failure to assess for adverse effects within 1-2 weeks
2. Excessive dosing: Starting with full doses rather than titrating gradually
3. Overlooking drug interactions: Not adjusting for potential pharmacokinetic interactions
4. Ignoring seizure risk: Bupropion lowers seizure threshold, especially at higher doses

The combination of bupropion and fluoxetine can be an effective strategy for patients with depression, particularly those with partial response to monotherapy or those experiencing sexual side effects from fluoxetine alone.