Can Cymbalta (duloxetine) and Wellbutrin (bupropion) be combined?

Combining Cymbalta and Wellbutrin

Yes, Cymbalta (duloxetine) and Wellbutrin (bupropion) can be safely combined in most patients, particularly for treatment-resistant depression, as this combination targets complementary neurotransmitter systems and may provide better efficacy than either medication alone. This combination is supported by clinical guidelines and research evidence.

Pharmacological Rationale

• Complementary mechanisms of action:

  • Cymbalta (duloxetine): Serotonin-norepinephrine reuptake inhibitor (SNRI)
  • Wellbutrin (bupropion): Norepinephrine-dopamine reuptake inhibitor (NDRI)
  • The combination provides broader neurotransmitter coverage (serotonin, norepinephrine, and dopamine) 1

• Dosing considerations:

  • Duloxetine: Starting dose 30-60 mg daily; can increase to 60-120 mg daily
  • Bupropion: Starting dose 100-150 mg daily; can increase to 150-450 mg daily 1

Evidence for Efficacy

The combination of antidepressants with different mechanisms of action is a recognized strategy for treatment-resistant depression. Clinical guidelines acknowledge that combining antidepressants that engage separate mechanisms of action can be effective for patients who don't respond adequately to monotherapy 2.

Case reports and clinical experience have shown that combining serotonergic antidepressants with bupropion can convert partial response to full response in treatment-resistant depression 3.

Safety Considerations

1. Serotonin syndrome risk:

   • While rare, there have been reports of serotonin syndrome with bupropion combined with SSRIs 4
   • Monitor for symptoms: mental status changes, neuromuscular hyperactivity, autonomic instability

2. Seizure threshold:

   • Bupropion can lower seizure threshold
   • Use with caution in patients with seizure disorders or risk factors 5

3. Blood pressure and heart rate:

   • Both medications can affect blood pressure and heart rate
   • Regular monitoring is recommended, especially during the first 12 weeks 5

4. Drug interactions:

   • Bupropion inhibits CYP2D6, which could potentially increase duloxetine levels
   • Start with lower doses and titrate slowly 5

Monitoring Protocol

• Initial phase (first 4-8 weeks):

  • Weekly monitoring of blood pressure, heart rate
  • Assessment of side effects and therapeutic response
  • Watch for signs of serotonin syndrome

• Maintenance phase:

  • Monthly monitoring until stable
  • Then every 3-6 months

Common Side Effects to Monitor

• Nausea, constipation, dry mouth
• Insomnia, anxiety, agitation
• Sexual dysfunction
• Increased sweating
• Headache, dizziness

When to Avoid This Combination

• Uncontrolled hypertension
• Seizure disorders
• Use of MAOIs within 14 days
• Severe hepatic impairment
• Pregnancy or breastfeeding

Alternative Approaches

If this combination is contraindicated or poorly tolerated, consider:

• Augmentation with mood stabilizers or atypical antipsychotics
• Switching to a different class of antidepressants
• Non-pharmacological approaches (psychotherapy, TMS, ECT)

This combination should be approached with careful monitoring but represents a rational pharmacological strategy for patients who have not responded adequately to monotherapy with either agent alone.