Can you mix Cymbalta (duloxetine) and Wellbutrin (bupropion)?

Combining Cymbalta (Duloxetine) and Wellbutrin (Bupropion)

Yes, Cymbalta (duloxetine) and Wellbutrin (bupropion) can be safely combined, but require careful monitoring for potential side effects including serotonin syndrome. 1

Rationale for Combination

The combination of duloxetine (an SNRI) and bupropion (an NDRI) can be therapeutically beneficial because:

• They work through complementary mechanisms: duloxetine affects serotonin and norepinephrine, while bupropion affects norepinephrine and dopamine
• This combination is sometimes used for treatment-resistant depression or when multiple symptoms need to be addressed 1

Dosing Recommendations

• Starting doses:

  • Duloxetine: 30-60 mg daily
  • Bupropion: 100-150 mg daily 1

• Maintenance doses:

  • Duloxetine: 60-120 mg daily
  • Bupropion: 150-450 mg daily 1

Monitoring Requirements

• Initial phase (first 1-2 weeks):

  • Monitor closely for signs of serotonin syndrome (mental status changes, neuromuscular hyperactivity, autonomic instability) 1
  • Weekly monitoring for suicidal ideation during the first month 1

• Ongoing monitoring:

  • Blood pressure and heart rate (both medications can affect cardiovascular parameters) 1
  • Mood and behavior changes 1
  • Side effects specific to each medication

Potential Side Effects

• Common side effects:

  • Nausea, constipation, headache
  • Dizziness, insomnia, dry mouth
  • Sexual dysfunction (more common with duloxetine)
  • Increased blood pressure 1

• Serious concerns:

  • Serotonin syndrome risk (although rare with this specific combination) 2
  • Seizure risk (bupropion lowers seizure threshold)
  • Increased blood pressure and heart rate

Important Precautions

• Contraindications:

  • Concurrent use with MAOIs (must be separated by at least 14 days)
  • Uncontrolled hypertension
  • Seizure disorders 1

• Use with caution in:

  • Hepatic impairment
  • Conditions that lower seizure threshold
  • Patients requiring opioid analgesia (naltrexone component in Contrave formulations of bupropion) 1

Drug Interactions

• Bupropion inhibits CYP2D6, which may increase blood levels of duloxetine 2
• This interaction could potentially increase the risk of side effects
• Avoid adding other serotonergic medications to this combination

Clinical Decision Algorithm

1. Before starting combination:

   • Ensure no contraindications exist
   • Establish baseline blood pressure, heart rate
   • Consider starting one medication first, then adding the second

2. Titration approach:

   • Start with lower doses of both medications
   • Increase gradually based on response and tolerability
   • Allow 1-2 weeks between dose adjustments

3. If side effects occur:

   • For mild side effects: consider dose reduction
   • For signs of serotonin syndrome: discontinue one or both medications and seek immediate medical attention

4. Discontinuation:

   • Taper gradually rather than stopping abruptly
   • Consider tapering one medication at a time if discontinuing both

While this combination can be effective, the potential for drug interactions and side effects requires careful monitoring and appropriate dosing adjustments.