Is Wellbutrin (bupropion) safe to take with fluoxetine?

Bupropion and Fluoxetine Combination Safety

Bupropion (Wellbutrin) can be safely used with fluoxetine, but requires careful monitoring due to potential drug interactions, particularly because bupropion inhibits CYP2D6 enzymes that metabolize fluoxetine. 1

Drug Interaction Mechanism

Bupropion and fluoxetine interact through the following mechanisms:

• Bupropion inhibits CYP2D6, which can increase fluoxetine concentrations in the body 1
• This interaction may lead to increased side effects from fluoxetine
• The combination affects both serotonergic (fluoxetine) and dopaminergic/noradrenergic (bupropion) neurotransmitter systems

Safety Considerations

Potential Benefits

• The combination may be beneficial for patients with depression who have:
  • Partial response to either medication alone 2
  • Sexual dysfunction from fluoxetine (bupropion may counteract this) 3
  • Need for augmentation therapy for treatment-resistant depression

Monitoring Requirements

• Monitor for increased side effects, particularly:
  • Insomnia and agitation
  • Blood pressure and heart rate changes
  • Seizure risk (bupropion lowers seizure threshold) 4
  • Sexual dysfunction (though bupropion may actually improve SSRI-induced sexual dysfunction) 3

Dosing Considerations

• Start with lower doses of both medications
• Consider administering bupropion in the morning to minimize insomnia
• Regular follow-up within 1-2 weeks of initiation to assess for adverse effects 5

Evidence from Guidelines and Research

The American College of Physicians guidelines acknowledge that both medications are used for weight loss and depression treatment, though they don't specifically address their combination 5. However, the FDA drug label for bupropion specifically mentions the interaction with fluoxetine, indicating this is a recognized combination that requires monitoring 1.

Research studies have shown:

• The combination can be effective for treatment-resistant depression 2
• In one study, 78% of patients showed clinical benefit when bupropion was added to existing SSRI therapy (including fluoxetine) 3
• Both medications have similar efficacy when used individually for depression 6

Contraindications and Precautions

Avoid this combination in patients with:

• History of seizures
• Recent MAO inhibitor use
• Uncontrolled hypertension
• Severe anxiety disorders
• History of stimulant abuse 4

Practical Recommendations

1. Begin with established doses of one medication before adding the second
2. Monitor for side effects at each follow-up visit, particularly during the first few weeks
3. If side effects occur, consider reducing the dose of one or both medications
4. Be aware that bupropion may increase fluoxetine levels due to CYP2D6 inhibition 1
5. The combination may actually improve sexual dysfunction caused by fluoxetine alone 3

This combination is generally considered safe with appropriate monitoring, and may offer advantages for patients who haven't responded adequately to either medication alone.