Switching from Lexapro (Escitalopram) to Wellbutrin (Bupropion)
No washout period is required when switching from escitalopram to bupropion—you can start bupropion immediately after stopping Lexapro, though a gradual taper of escitalopram over 10-14 days is recommended to minimize discontinuation symptoms.
Direct Switch Strategy
The FDA labeling for both medications provides clear guidance on this transition:
Bupropion (Wellbutrin) does NOT require a washout period when switching from SSRIs like escitalopram 1. The 14-day washout requirement only applies when switching to or from MAOIs, not between different antidepressant classes 1.
Escitalopram (Lexapro) can be discontinued without a mandatory drug-free interval before starting bupropion, as these medications work through different mechanisms (serotonin reuptake inhibition vs. dopamine/norepinephrine reuptake inhibition) 2.
Recommended Tapering Approach
While no washout is needed, taper escitalopram gradually to avoid discontinuation syndrome 3, 4:
- Reduce escitalopram dose over 10-14 days before complete cessation 4
- For patients on 20 mg daily: reduce to 10 mg for 7 days, then discontinue
- For patients on 10 mg daily: reduce to 5 mg for 7 days, then discontinue
- Start bupropion on the same day you begin the taper or immediately after the last escitalopram dose
Bupropion Initiation During Taper
Begin bupropion at 150 mg once daily in the morning 1:
- After 4 days, may increase to target dose of 300 mg once daily
- Take in the morning to minimize insomnia risk 4
- Can be started while tapering escitalopram—no drug interaction concerns
Critical Monitoring Points
Monitor closely for discontinuation symptoms in the first 1-2 weeks 2:
- Dizziness, fatigue, headaches, nausea
- Anxiety, irritability, sensory disturbances
- These symptoms indicate escitalopram withdrawal, not bupropion side effects
Watch for neuropsychiatric changes with bupropion initiation 5:
- Increased agitation or activation (bupropion is activating) 4
- Worsening depression or suicidal ideation
- Insomnia (give second dose before 3 PM if using twice-daily formulation) 4
Common Pitfalls to Avoid
Do not use alternate-day dosing when tapering escitalopram—this causes severe receptor occupancy fluctuations and worsens withdrawal symptoms 6, 7. Use daily reduced doses instead.
Do not confuse this switch with MAOI transitions—the 14-day washout only applies to MAOIs, not SSRI-to-bupropion switches 1.
Contraindications for bupropion: Do not use in patients with seizure disorders, eating disorders (bulimia/anorexia), or those abruptly discontinuing alcohol or benzodiazepines 5, 1.
Why This Approach Works
Escitalopram and bupropion have no significant pharmacodynamic interactions—escitalopram primarily affects serotonin while bupropion affects dopamine and norepinephrine 8. The gradual taper of escitalopram prevents withdrawal symptoms while bupropion provides immediate antidepressant coverage, avoiding a treatment gap that could lead to depressive relapse 9, 7.