Can a patient currently taking Lexapro (escitalopram) be started on Wellbutrin (bupropion)?

Can You Start Wellbutrin on Someone Taking Lexapro?

Yes, you can safely start Wellbutrin (bupropion) in a patient currently taking Lexapro (escitalopram), and this combination is a well-established augmentation strategy for depression that has not adequately responded to SSRI monotherapy alone. 1, 2

Evidence Supporting Combination Therapy

The combination of escitalopram and bupropion demonstrates superior efficacy compared to SSRI monotherapy:

• Augmenting SSRIs with bupropion decreases depression severity more effectively than other augmentation strategies (such as buspirone), with remission rates of approximately 50% and response rates of 62% in patients with chronic or recurrent major depressive disorder. 1, 2

• A pilot study of 51 outpatients treated with escitalopram plus bupropion-SR showed these combination remission rates were significantly higher than typical SSRI monotherapy, with only 6% discontinuing due to side effects. 2

• This combination addresses depression through complementary mechanisms: escitalopram affects serotonin pathways while bupropion works via noradrenergic and dopaminergic pathways. 1

Practical Dosing Protocol

Start with a conservative titration approach to minimize adverse effects:

• Begin bupropion at 37.5 mg every morning, increasing by 37.5 mg every 3 days as tolerated. 1
• Target dose is 150 mg twice daily (maximum 300-400 mg/day for SR formulation). 1, 2
• Administer the second dose before 3 PM to minimize insomnia risk, as bupropion has activating properties. 1
• The mean effective dose in combination studies was approximately 327-329 mg/day of bupropion-SR, achieved by week 8. 2

Critical Safety Screening Before Initiation

You must screen for absolute contraindications before prescribing bupropion:

• Seizure history or any condition predisposing to seizures (brain metastases, head trauma, brain tumor, stroke) - bupropion lowers seizure threshold with risk of approximately 0.1% at therapeutic doses. 1, 3, 4
• Eating disorders (bulimia or anorexia nervosa) - significantly increased seizure risk. 1, 4
• Current or recent MAOI use (within 14 days). 1
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs - absolute contraindication due to increased seizure risk. 1
• Uncontrolled hypertension - bupropion can elevate blood pressure and heart rate. 1
• Moderate to severe hepatic or renal impairment - requires dose reduction. 1

Important Drug Interaction Considerations

While escitalopram and bupropion can be safely combined, be aware of these interactions:

• Both medications can lower seizure threshold, so strict adherence to maximum dosing guidelines is essential - do not exceed 450 mg/day of bupropion to maintain seizure risk at 0.1%. 1, 3
• Bupropion may inhibit cytochrome P450 2D6, potentially affecting escitalopram metabolism, though this combination does not have significant pharmacokinetic interactions that preclude their use together. 1, 5
• Use extreme caution if the patient is on other medications that lower seizure threshold (such as antipsychotics like clozapine). 6

Monitoring Parameters

Implement the following monitoring schedule:

• Monitor within 1-2 weeks of initiation for worsening depression, suicidal ideation, or behavioral changes - particularly critical in patients under 24 years of age, as suicide risk is greatest during the first 1-2 months of treatment. 1
• Monitor blood pressure and heart rate periodically, especially in the first 12 weeks, as bupropion can cause elevations in both parameters. 1
• Assess for neuropsychiatric adverse effects including agitation and restlessness, as bupropion is an activating medication. 1
• Allow 6-8 weeks at adequate doses before determining treatment response - do not discontinue prematurely unless significant adverse effects occur. 1

Clinical Advantages of This Combination

This combination may be particularly beneficial for patients with:

• Low energy, apathy, or hypersomnia - bupropion's activating properties can improve these symptoms. 1
• Sexual dysfunction from SSRI therapy - bupropion has significantly lower rates of sexual dysfunction compared to SSRIs. 1
• Weight gain concerns - bupropion is associated with minimal weight gain or even weight loss, unlike many other antidepressants. 1
• Comorbid smoking cessation needs - bupropion addresses both depression and nicotine dependence simultaneously. 1

Common Pitfalls to Avoid

• Do not start bupropion late in the day - the activating properties can cause insomnia if dosed after 3 PM. 1
• Do not exceed maximum daily doses - seizure risk increases significantly above 450 mg/day. 1, 3
• Do not overlook seizure risk factors - even at therapeutic doses, bupropion was the third leading cause of drug-related new-onset seizures in one emergency department study, with all cases occurring at ≤450 mg/day. 4
• Do not ignore the black box warning - increased risk of suicidal thoughts and behavior in patients younger than 24 years requires close monitoring. 1