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

Combining Cymbalta and Wellbutrin: Safety and Efficacy

Yes, Cymbalta (duloxetine) and Wellbutrin (bupropion) can be safely used together, and this combination is often employed to enhance antidepressant response or address specific symptom profiles that don't respond adequately to monotherapy.

Pharmacological Rationale

The combination works well because these medications have complementary mechanisms of action:

• Duloxetine (Cymbalta): A serotonin-norepinephrine reuptake inhibitor (SNRI) that primarily affects serotonin and norepinephrine neurotransmission 1
• Bupropion (Wellbutrin): A dopamine and norepinephrine reuptake inhibitor with minimal effects on serotonergic activity 2

This combination provides coverage across three major neurotransmitter systems (serotonin, norepinephrine, and dopamine), which may be particularly beneficial for patients with treatment-resistant depression or specific symptom profiles.

Clinical Applications

This combination is particularly useful in several scenarios:

• Treatment-resistant depression: When monotherapy with either medication has provided inadequate response 3, 4
• Specific symptom targeting:
  • When a patient has residual symptoms like fatigue, low motivation, or anhedonia despite SNRI therapy 5
  • For patients with comorbid pain syndromes (where duloxetine excels) and energy/motivation issues (where bupropion excels) 1, 5
• Sexual dysfunction: Bupropion can help counteract the sexual side effects commonly associated with SNRIs 4

Safety Considerations

While generally safe, there are important precautions:

• Drug interactions: Both medications inhibit CYP2D6, which may increase blood levels of each drug 2, 6
• Seizure risk: Bupropion carries a seizure risk of approximately 0.1%, so use caution in patients with seizure disorders 5
• Serotonin syndrome: Although rare, cases have been reported with bupropion combined with serotonergic agents 2
• Blood pressure/pulse: Both medications can affect blood pressure and heart rate, requiring monitoring 1
• Delirium risk: Particularly in elderly patients due to drug-drug interactions 6

Dosing and Administration

When combining these medications:

1. Start low and titrate slowly: Begin with established doses of one medication before adding the second
2. Monitor closely: Check for side effects, particularly during the initial combination period
3. Timing considerations: Administer the second daily dose of bupropion before 3 PM to minimize insomnia risk 5
4. Evaluate response: Assess efficacy after 7-12 weeks at therapeutic doses 5

Monitoring Recommendations

• Regular assessment of blood pressure and pulse
• Monitor for signs of serotonin syndrome (confusion, agitation, muscle twitching, sweating, shivering)
• Assess for improvement in target symptoms
• Evaluate for side effects specific to each medication

Contraindications

Absolute contraindications to this combination include:

• Concurrent use of MAOIs 1, 5
• Uncontrolled seizure disorders 5
• History of anorexia or bulimia 5
• Severe uncontrolled hypertension

Evidence Summary

Multiple studies support this combination:

• Case reports demonstrate efficacy in treatment-resistant depression 3, 7
• Research indicates the combination can boost antidepressant response when monotherapy is inadequate 4
• Clinical guidelines acknowledge the role of combination therapy for specific symptom profiles 5

Conclusion

The combination of Cymbalta and Wellbutrin represents a rational pharmacological approach for patients with depression who have not achieved adequate response to monotherapy or who have specific symptom profiles that may benefit from targeting multiple neurotransmitter systems. While generally safe when properly monitored, careful attention to potential drug interactions and side effects is essential.