Switching from Wellbutrin to Lexapro: Timing and Safety
You can start Lexapro (escitalopram) immediately after stopping Wellbutrin (bupropion) without any required washout period. Unlike switching between SSRIs or when dealing with MAOIs, there is no pharmacological reason to wait between discontinuing bupropion and initiating escitalopram.
Why No Washout Is Required
Bupropion and escitalopram work through completely different mechanisms and do not create dangerous interactions:
- Bupropion primarily affects norepinephrine and dopamine reuptake, while escitalopram selectively inhibits serotonin reuptake 1
- Neither medication is a monoamine oxidase inhibitor (MAOI), which would require a 14-day washout period 2, 3
- Escitalopram has minimal effects on cytochrome P450 enzymes and low potential for drug-drug interactions 1
- The combination of these two medications is actually commonly used together and is well-tolerated, with clinical trials demonstrating safety when both are administered simultaneously 4, 5, 6
Evidence Supporting Immediate Transition
Multiple high-quality studies have demonstrated the safety of combining bupropion and escitalopram from treatment initiation:
- A 2018 randomized controlled trial showed patients could receive both medications together from day one, with escitalopram up to 40 mg/day and bupropion up to 450 mg/day, demonstrating good tolerability 5
- A 2008 pilot study started patients on escitalopram 10 mg/day, then added bupropion-SR at week 1, with only 6% discontinuing due to side effects 4
- Electrophysiological studies in rats confirmed that co-administration of these medications does not produce dangerous neurochemical interactions 7
Critical Safety Considerations Before Starting Lexapro
Before initiating escitalopram, verify the patient does not have contraindications:
- Confirm no current or recent MAOI use (within 14 days), as combining SSRIs with MAOIs can cause life-threatening serotonin syndrome with symptoms appearing within 24-48 hours 2
- Screen for other serotonergic medications that could increase serotonin syndrome risk, including tramadol, meperidine, methadone, fentanyl, dextromethorphan, and St. John's wort 2
- Assess for conditions that prolong QT interval, as citalopram (though less so with escitalopram) can cause QT prolongation at higher doses 2
Recommended Transition Protocol
Start escitalopram 10 mg once daily on the day after stopping bupropion:
- Escitalopram reaches steady-state concentrations within 7-10 days, with maximum plasma concentrations occurring 3-4 hours after dosing 1
- The elimination half-life of escitalopram is 27-33 hours, consistent with once-daily dosing 1
- Bupropion's shorter half-life means it will clear relatively quickly, but this does not necessitate waiting to start escitalopram 3
Monitoring During the Transition
Close follow-up is essential in the first 1-2 weeks after any antidepressant change:
- Monitor for worsening depression, suicidal ideation, or behavioral changes, particularly in patients under 24 years of age 3
- Assess for early signs of serotonin syndrome: mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 2
- Evaluate therapeutic response and adverse effects within 1-2 weeks of initiating escitalopram 3
- Allow 6-8 weeks at an adequate dose before determining treatment response 3
Common Pitfall to Avoid
Do not confuse this switch with MAOI transitions, which require mandatory washout periods. The 14-day washout requirement applies only when switching to or from MAOIs (phenelzine, isocarboxazid, moclobemide, isoniazid, linezolid), not when switching between bupropion and SSRIs 2, 3. This is a critical distinction that prevents unnecessary delays in treatment.