Is it safe for an otherwise healthy adult to take escitalopram (Lexapro) 20 mg daily combined with bupropion (Wellbutrin) 150 mg daily?

Combining Escitalopram 20 mg with Bupropion 150 mg: Safety and Clinical Guidance

Yes, combining escitalopram (Lexapro) 20 mg daily with bupropion (Wellbutrin) 150 mg daily is safe and effective for otherwise healthy adults with major depressive disorder. This combination is a well-established augmentation strategy supported by clinical guidelines and research evidence.

Evidence Supporting This Combination

The American College of Physicians recognizes this combination as an effective augmentation strategy for treatment-resistant depression, with low-quality evidence demonstrating that augmenting SSRIs with bupropion decreases depression severity more effectively than other augmentation approaches like buspirone. 1

• In the STAR*D trial, augmentation with bupropion resulted in significantly lower discontinuation rates due to adverse events (12.5%) compared to buspirone augmentation (20.6%, P < 0.001), indicating superior tolerability. 1

• An open pilot study of 51 outpatients treated with escitalopram plus bupropion-SR achieved response rates of 62% and remission rates of 50%, which are significantly higher than typical SSRI monotherapy outcomes. 2

• The combination addresses depression through complementary mechanisms: escitalopram enhances serotonergic activity while bupropion works via noradrenergic and dopaminergic pathways. 1

Critical Safety Screening Before Continuing

Before continuing this combination, verify the patient does not have absolute contraindications to bupropion: 1, 3

• Seizure disorders or any condition predisposing to seizures (history of head trauma, brain tumor, stroke)
• Current or recent MAOI use (within 14 days of discontinuation)
• Eating disorders (bulimia or anorexia nervosa)
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs
• Uncontrolled hypertension
• Moderate to severe hepatic or renal impairment

Dosing Considerations

The current regimen of escitalopram 20 mg daily with bupropion 150 mg daily represents appropriate dosing within therapeutic ranges: 1

• Escitalopram dosing typically ranges from 10-20 mg/day, so 20 mg is at the maximum recommended dose. 1

• Bupropion 150 mg daily is a starting dose; the standard therapeutic dose for depression is 300 mg/day (150 mg twice daily for SR formulation). 1

• If the patient is taking bupropion SR 150 mg once daily, consider titrating to 150 mg twice daily (300 mg total) after 3-7 days if tolerated, as this is the standard therapeutic dose for major depressive disorder. 1

• The maximum dose of bupropion should not exceed 450 mg/day to maintain seizure risk at approximately 0.1%. 1, 3

Monitoring Parameters

Blood pressure and heart rate must be monitored periodically, especially during the first 12 weeks, because bupropion can cause elevations in both parameters. 1

During the first 1-2 weeks after starting or adjusting this combination, assess for: 1

• Suicidal ideation, agitation, irritability, or unusual behavioral changes (highest risk period for suicide attempts)
• Neuropsychiatric symptoms including increased agitation or restlessness
• Signs of serotonin syndrome (though risk is low with this combination): mental status changes, neuromuscular hyperactivity, autonomic hyperactivity

Expected Timeline for Clinical Response

Maintain the combination at therapeutic doses for 6-8 weeks before evaluating overall treatment response. 1

• Early improvement in energy levels may occur within the first few weeks with bupropion. 1

• Full antidepressant efficacy typically emerges by 6-8 weeks. 1

• If no adequate response occurs by 6-8 weeks at therapeutic doses, modify the treatment approach by adjusting doses or considering alternative augmentation strategies. 1

Clinical Advantages of This Combination

Bupropion offers distinct advantages that complement escitalopram: 1

• Significantly lower rates of sexual dysfunction compared to SSRIs alone—bupropion may actually counteract SSRI-induced sexual dysfunction. 1

• Minimal weight gain or even weight loss, unlike many SSRIs that cause weight gain. 1

• Lower rates of sedation and activating properties that can improve energy levels and reduce apathy. 1

• Addresses both dopaminergic/noradrenergic and serotonergic pathways, providing broader neurotransmitter coverage. 1

Timing of Bupropion Administration

If taking bupropion SR formulation twice daily, administer the first dose in the morning and the second dose before 3 PM to minimize insomnia risk. 1

• Bupropion has activating properties that make morning administration ideal. 1

• Late-day dosing increases the risk of sleep disturbances. 1

Important Clinical Pitfalls to Avoid

Do not skip the intensive monitoring window during weeks 1-2, as this period carries the highest risk for emergent suicidal ideation, especially in patients younger than 24 years. 1

Do not exceed a total bupropion dose of 450 mg/day, as seizure risk rises markedly above this threshold. 1, 3

Do not discontinue treatment prematurely before 6-8 weeks unless significant adverse effects occur. 1

Both medications can lower seizure threshold, so strict adherence to maximum dosing guidelines is essential. 1

Contraindication Note on Combination Products

This safety guidance applies to bupropion monotherapy combined with escitalopram—it does NOT apply to naltrexone-bupropion combination products, which have different contraindications including any opioid therapy. 1