What is the protocol for transitioning from citalopram (Celexa) to bupropion (Wellbutrin)?

Protocol for Transitioning from Citalopram to Bupropion

You can directly switch from citalopram to bupropion without a washout period, using either a conservative taper-then-start approach or a cross-taper method, as these medications have minimal pharmacokinetic interaction risk. 1

Switching Strategy Options

Option 1: Conservative Taper-Then-Start (Lower Risk)

• Gradually taper citalopram over 1-2 weeks by reducing the dose incrementally (e.g., if on 40 mg, reduce to 20 mg for 5-7 days, then 10 mg for 5-7 days) 1, 2
• Start bupropion 1-2 days after the last citalopram dose to minimize any treatment gap while allowing for citalopram clearance 1, 2
• This approach reduces withdrawal symptoms and allows monitoring between medications 2

Option 2: Direct Cross-Taper (Faster Transition)

• Begin bupropion while still on citalopram, starting at 37.5-150 mg once daily 1
• Simultaneously begin tapering citalopram over 1-2 weeks as bupropion is titrated upward 2
• This method is safe because bupropion and citalopram have different mechanisms (dopamine/norepinephrine vs. serotonin) with minimal interaction risk 1
• Evidence from the STAR*D trial supports the safety and efficacy of this approach 1

Bupropion Dosing Schedule

• Initial dose: 37.5-150 mg once daily in the morning (lower starting dose if cross-tapering) 1
• Increase by 37.5-150 mg every 3 days as tolerated 1
• Target dose: 150 mg twice daily (maximum 300 mg/day in divided doses) 1
• Give second dose before 3 PM to minimize insomnia risk 1

Critical Safety Considerations

Contraindications for Bupropion

• Do not use in patients with seizure disorders, brain metastases, or stroke history due to dose-dependent seizure risk 1
• Contraindicated with concurrent MAO inhibitor use (increased hypertensive reaction risk) 1
• Avoid in highly agitated patients as bupropion is activating 1

Monitoring Requirements

• Monitor for neuropsychiatric symptoms including worsening depression, suicidal ideation, hostility, or behavioral changes during the transition 1
• Assess for withdrawal symptoms from citalopram discontinuation (dizziness, nausea, headache, irritability) and manage supportively 2
• Watch for activation symptoms from bupropion (insomnia, anxiety, restlessness) especially in the first 2 weeks 1

Evidence-Based Rationale

The STAR*D trial demonstrated equivalent efficacy when switching from citalopram to bupropion SR compared to other second-generation antidepressants (sertraline, venlafaxine), with no significant differences in response or remission rates 1. Importantly, bupropion had lower discontinuation rates due to adverse events (12.5%) compared to buspirone augmentation (20.6%) when added to citalopram 1, 3.

Combination therapy data shows that citalopram plus bupropion can be safely co-administered, supporting the safety of cross-tapering 3, 4, 5, 6. One study found synergistic antidepressant effects with the combination 4, and another reported 28% remission rates with combination versus 7% with monotherapy switching 6.

Common Pitfalls to Avoid

• Do not abruptly discontinue citalopram after prolonged use, as this increases withdrawal syndrome risk 2
• Do not exceed 400 mg/day total bupropion dose or give doses too close together (maintain 8-hour intervals minimum) to reduce seizure risk 1
• Do not dismiss early activation symptoms as treatment failure; these often resolve within 1-2 weeks 1
• Do not forget that therapeutic response requires 4-8 weeks for full assessment 1