Can bupropion be given with citalopram (Celexa)?

Bupropion and Citalopram Combination Therapy

Bupropion can be safely administered with citalopram, but caution is required due to potential drug interactions and increased risk of side effects. 1

Pharmacological Considerations

Drug Interactions

• Bupropion can increase citalopram levels by approximately 30-40% through CYP2D6 inhibition 1
• This interaction requires careful monitoring but does not constitute an absolute contraindication
• Citalopram does not significantly affect the pharmacokinetics of bupropion and its metabolites 1

Safety Concerns

• The combination increases the theoretical risk of serotonin syndrome, though this is rare with this specific combination 2
• Citalopram may cause QT prolongation at doses exceeding 40mg/day and should be used cautiously in patients with cardiac conditions 3
• Bupropion lowers seizure threshold, with risk increasing at doses above 450mg/day 4

Clinical Recommendations

Dosing Strategy

1. Start with lower doses of both medications:
   • Begin citalopram at 10mg daily
   • Add bupropion at 150mg daily (preferably SR formulation)
2. Titrate gradually:
   • Increase bupropion by 150mg increments every 7 days as tolerated
   • Maximum recommended bupropion dose: 400mg/day 5
   • Maximum recommended citalopram dose: 40mg/day 3

Monitoring Requirements

• Monitor for signs of serotonin syndrome during the first 24-48 hours after dosage changes 3
  • Early symptoms: agitation, tremor, hyperreflexia, myoclonus
  • Severe symptoms: hyperthermia, rigidity, autonomic instability
• Watch for increased side effects from either medication due to drug interaction
• Assess QT interval if patient has cardiac risk factors or is on high-dose citalopram

Clinical Applications

Therapeutic Benefits

• This combination may be particularly effective for:
  • Treatment-resistant depression 6
  • Depression with prominent fatigue or low energy 7
  • Patients experiencing sexual dysfunction on citalopram alone 7

Contraindications

• Absolute contraindications:
  • Concurrent use of MAOIs 3
  • History of seizure disorders 4
  • Eating disorders with purging behaviors
• Relative contraindications:
  • Uncontrolled hypertension
  • Severe hepatic impairment
  • Long QT syndrome 3

Evidence Summary

The combination of bupropion and SSRIs like citalopram has shown efficacy in clinical practice, particularly for treatment-resistant depression 7, 6. Open-label studies suggest response rates of approximately 62% and remission rates of 50% when combining bupropion with an SSRI 5. This combination can also help mitigate SSRI-induced sexual dysfunction and address symptoms like fatigue that may persist with SSRI monotherapy 7.

Common Pitfalls to Avoid

• Starting both medications simultaneously (instead, start one and stabilize before adding the second)
• Rapid dose escalation increasing risk of adverse effects
• Failing to recognize early signs of serotonin syndrome
• Overlooking potential drug interactions with other medications metabolized by CYP2D6
• Using in patients with seizure disorders or those taking other medications that lower seizure threshold

The evidence supports that while this combination requires careful monitoring, it can be an effective strategy for patients who have had inadequate response to monotherapy with either agent.