Can Cymbalta (duloxetine) and Wellbutrin (bupropion) be taken together?

Combining Cymbalta (Duloxetine) and Wellbutrin (Bupropion)

Yes, Cymbalta (duloxetine) and Wellbutrin (bupropion) can be safely combined for treatment of depression, particularly in cases where monotherapy has produced an incomplete response.

Pharmacological Rationale

• Duloxetine (Cymbalta) is a serotonin-norepinephrine reuptake inhibitor (SNRI) that works by inhibiting the reuptake of both serotonin and norepinephrine 1
• Bupropion (Wellbutrin) has a distinct mechanism of action as a dopamine/norepinephrine reuptake inhibitor, providing complementary neurotransmitter effects 1
• The combination provides broader neurotransmitter coverage (serotonin, norepinephrine, and dopamine), which may lead to improved efficacy in treatment-resistant cases 1, 2

Evidence for Efficacy

• Clinical studies support that combining bupropion with serotonergic antidepressants (including SNRIs like duloxetine) can boost antidepressant response in patients who have had partial response to monotherapy 1
• In treatment-refractory depression, combination therapy with bupropion and serotonergic agents has shown improved outcomes compared to monotherapy 3
• One study demonstrated that approximately 70% of patients experienced greater symptomatic improvement with combined therapy than with either agent alone 2
• A double-blind randomized study found that antidepressant combinations from treatment initiation approximately doubled the likelihood of remission compared to monotherapy 4

Safety Considerations

• The combination of bupropion with SNRIs is generally well-tolerated according to available clinical data 1, 2

• Common side effects to monitor include:

  • Sexual dysfunction (41% incidence in one study) 2
  • Insomnia (22% incidence) 2
  • Fatigue/anergy (15% incidence) 2
  • Tremor (11% incidence) 2
  • Gastrointestinal effects from both medications 1

• Important precautions:

  • Bupropion lowers seizure threshold, so caution is needed in patients with seizure disorders 5
  • The combination may potentially increase blood pressure and heart rate, requiring monitoring 5, 1
  • Risk of serotonin syndrome, though this appears to be rare with this specific combination 1

Dosing Considerations

• When combining these medications:
  • Start with lower doses of each medication and titrate gradually 6
  • In clinical studies, effective combinations used moderate doses (e.g., bupropion 150-300 mg/day with standard SNRI dosing) 4, 2
  • Monitor closely for side effects during the initial combination period 1

Clinical Pearls

• This combination may be particularly helpful for patients with:

  • Incomplete response to either medication alone 1, 2
  • Persistent fatigue or lack of motivation on duloxetine alone (bupropion may help with these symptoms) 1
  • Sexual dysfunction from duloxetine (bupropion may help mitigate these side effects) 1

• Common pitfalls to avoid:

  • Initiating both medications simultaneously at full doses (increases risk of side effects) 6
  • Using in patients with poorly controlled seizure disorders or eating disorders 5
  • Failure to monitor for potential drug interactions with other medications 1

While this combination is not explicitly mentioned in current guidelines for first-line treatment, the evidence supports its use as a rational approach for patients with inadequate response to monotherapy, with acceptable safety when properly monitored.