How do I switch from escitalopram (Lexapro) to bupropion (Wellbutrin)?

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Switching from Escitalopram to Wellbutrin (Bupropion)

The safest approach is a cross-taper strategy: start bupropion SR at 150 mg once daily while maintaining your current escitalopram dose, increase bupropion to 150 mg twice daily after 3 days, then gradually taper escitalopram over 1-2 weeks. 1

Cross-Taper Protocol

Begin bupropion SR at 150 mg once daily in the morning while continuing your full escitalopram dose. 1 This allows the new medication to reach therapeutic levels before discontinuing the SSRI, minimizing the risk of depressive relapse during the transition. 2

After 3 days on bupropion 150 mg daily, increase to the target dose of 150 mg twice daily (300 mg total daily). 1 Take the second dose before 3 PM to minimize insomnia risk. 3, 1

Once bupropion reaches 300 mg daily and is well-tolerated, begin tapering escitalopram by reducing the dose by 50% for one week, then discontinuing. 2 Gradual tapering over days to weeks reduces withdrawal syndrome risk and severity. 2

Critical Timing Considerations

Do not abruptly stop escitalopram, as this can cause withdrawal symptoms including dizziness, nausea, headache, and mood changes. 2 The cross-taper approach prevents both SSRI withdrawal and gaps in antidepressant coverage that could trigger depressive relapse. 2

Conservative switching strategies that involve complete washout periods between medications can take weeks and include periods without treatment, risking potentially life-threatening exacerbations of depression. 2 The cross-taper avoids this pitfall while maintaining safety.

Contraindications to This Switch

Absolutely avoid bupropion if you have a seizure disorder, history of seizures, eating disorder (anorexia or bulimia), or are abruptly discontinuing alcohol or benzodiazepines. 1 Bupropion lowers seizure threshold, with risk increasing at doses above 450 mg daily. 3, 4

Do not use bupropion within 14 days of stopping a monoamine oxidase inhibitor (MAOI), as this combination can cause hypertensive crisis. 1

Exercise caution if you have uncontrolled hypertension, as bupropion can elevate blood pressure. 1

Dose Adjustments for Special Populations

For older adults, start bupropion at 37.5 mg daily and increase by 37.5 mg every 3 days to a maximum of 150 mg twice daily. 3, 1 This represents approximately 50% of the standard starting dose. 1

For patients with moderate to severe hepatic impairment, do not exceed 150 mg total daily dose of bupropion. 1

For patients with moderate to severe renal impairment, reduce the total daily bupropion dose by half. 1

Expected Side Effects and Management

Common bupropion side effects include insomnia, dry mouth, headache, nervousness, tremors, and nausea. 3, 1 These are typically mild and often resolve within 1-2 weeks. 3

Insomnia is the most common complaint—taking the second dose before 3 PM significantly reduces this risk. 3, 1 If insomnia persists, consider reducing the afternoon dose or switching to once-daily dosing at 150 mg. 3

Bupropion tends to be activating and may reduce apathy, making it particularly useful for patients with low energy depression. 3 However, do not use bupropion in highly agitated patients, as it can worsen agitation. 3

Monitoring During Transition

Schedule a follow-up visit within 2 weeks of initiating the switch to assess efficacy, side effects, and adherence. 3, 1 This early check-in allows for dose adjustments before problems escalate.

Monitor blood pressure at follow-up visits, particularly in patients with pre-existing hypertension. 1

Monitor closely for neuropsychiatric adverse effects, especially in patients younger than 24 years, including worsening depression, suicidal ideation, or unusual behavioral changes. 3, 1 While uncommon, these warrant immediate discontinuation if they occur. 3

Efficacy Timeline and Next Steps

A full therapeutic trial requires 4-8 weeks at the target dose before determining efficacy. 3, 1 Some patients may experience rapid improvement in energy levels within the first 1-2 weeks due to bupropion's activating properties. 3

If no response is seen after 6-8 weeks at an adequate bupropion dose (300 mg daily), consider switching to a different antidepressant or augmentation strategy. 1 Evidence from the STAR*D trial shows that switching between different antidepressant classes (including switching to bupropion) produces similar remission rates of approximately 25-30%. 3

Common Pitfalls to Avoid

Never exceed 450 mg total daily dose of bupropion, as seizure risk increases substantially above this threshold. 1, 4 One case report documented mania occurring only after exceeding 450 mg daily in a patient with bipolar disorder, suggesting dose-related toxicity. 4

Do not take bupropion late in the day—this is the most common cause of treatment-limiting insomnia. 1

Do not abruptly stop escitalopram without a taper, even when starting bupropion. 2 The cross-taper protects against both withdrawal symptoms and depressive relapse during the transition period.

Avoid combining bupropion with other medications that lower seizure threshold, including antipsychotics, theophylline, systemic corticosteroids, and stimulants. 1

References

Guideline

Safely Switching from Lexapro (Escitalopram) to Wellbutrin (Bupropion)

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Switching and stopping antidepressants.

Australian prescriber, 2016

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Mania with bupropion: a dose-related phenomenon?

The Annals of pharmacotherapy, 2000

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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