Can you take Cymbalta (duloxetine) with bupropion?

Combining Cymbalta (Duloxetine) with Bupropion

Yes, Cymbalta (duloxetine) can be taken with bupropion, but this combination requires careful monitoring due to potential drug interactions and increased risk of side effects. 1, 2

Pharmacological Rationale

• Both medications work through different mechanisms: duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI), while bupropion primarily affects dopamine and norepinephrine 1, 3
• This combination is sometimes used in clinical practice to enhance antidepressant response or to counteract SNRI-associated sexual dysfunction 2

Potential Benefits

• The combination may provide better symptom control when monotherapy is inadequate 2
• Bupropion may help reduce sexual side effects commonly associated with SNRIs like duloxetine 2
• The different mechanisms of action may provide complementary effects on mood regulation 3

Important Risks and Monitoring

• Both medications can inhibit CYP2D6 enzymes, potentially leading to higher levels of hydroxybupropion, which increases the risk of adverse effects 4, 3
• There is a case report of delirium occurring in an elderly patient when duloxetine and bupropion were used together 4
• Monitor for signs of:
  • Increased blood pressure and heart rate 1, 5
  • Seizures (bupropion lowers seizure threshold) 1, 3
  • Serotonin syndrome (agitation, hyperthermia, neuromuscular abnormalities) 1, 5
  • Behavioral activation or agitation 1

Contraindications

• History of seizures or conditions that lower seizure threshold 1
• Uncontrolled hypertension 1, 5
• Current use of MAOIs (monoamine oxidase inhibitors) 1, 5
• Severe hepatic impairment (duloxetine is associated with hepatic risks) 1

Dosing Considerations

• Start with lower doses of both medications when using in combination 1, 2
• Gradual dose titration is recommended to minimize side effects 1, 2
• If adverse effects occur, consider reducing the dose of one or both medications 2

Practical Approach

• Baseline assessment of blood pressure, heart rate, and liver function is advisable 1, 5
• Regular monitoring of vital signs and emergence of side effects, particularly during the initial weeks of combination therapy 1, 4
• Educate patients about potential side effects and when to seek medical attention 1
• Consider discontinuing one or both medications if intolerable side effects occur 4

Special Populations

• Use with extra caution in elderly patients who may be more susceptible to adverse effects, including delirium 4
• Patients with cardiovascular disease require closer monitoring due to potential effects on blood pressure and heart rate 1, 5