Can a patient take Lexapro (escitalopram) with Wellbutrin (bupropion)?

Can a Patient Take Lexapro with Wellbutrin?

Yes, combining Lexapro (escitalopram) with Wellbutrin (bupropion) is an established and commonly used treatment strategy for depression, particularly for treatment-resistant cases, and is generally well-tolerated with appropriate monitoring. 1, 2

Clinical Evidence Supporting Combination Therapy

The combination of escitalopram and bupropion is recognized by the American Academy of Family Physicians as an established treatment option for both bipolar depression and treatment-resistant depression. 2 This combination offers several therapeutic advantages:

• Enhanced efficacy: Open-label studies demonstrate remission rates of approximately 50% and response rates of 62% with this combination, which exceeds typical SSRI monotherapy outcomes. 3
• Sexual side effect mitigation: Bupropion can reverse SSRI-associated sexual dysfunction, a common reason for treatment discontinuation. 1
• Complementary mechanisms: The combination provides synergistic effects through distinct neurotransmitter systems—escitalopram enhances serotonergic activity while bupropion modulates dopamine and norepinephrine. 4

Safety Profile and Tolerability

The combination is generally well-tolerated with low discontinuation rates due to side effects (approximately 6%). 3 However, specific monitoring is required:

Common Side Effects to Anticipate

• Gastrointestinal effects: Nausea (most frequent reason for discontinuation), vomiting, diarrhea, and constipation are common. 1
• Neurological symptoms: Headache, dizziness, tremor, and insomnia occur regularly. 1
• Other effects: Dry mouth, fatigue, sweating, and agitation have been reported. 1

Critical Safety Concerns Requiring Monitoring

Seizure risk is the most important consideration with bupropion:

• Bupropion carries dose-dependent seizure risk, particularly at doses exceeding 300 mg/day. 1, 2
• Absolute contraindications include active seizure disorders, conditions lowering seizure threshold, eating disorders (anorexia/bulimia), and abrupt discontinuation of alcohol or benzodiazepines. 5, 2
• Maximum daily dose should not exceed 300 mg to minimize seizure risk. 2

Serotonin syndrome risk is theoretically possible but clinically low:

• Although bupropion primarily affects dopamine and norepinephrine (not serotonin), case reports have linked the combination to serotonin syndrome. 6
• Monitor for mental status changes, neuromuscular hyperactivity (rigidity, hyperreflexia, myoclonus), autonomic instability (fever, unstable blood pressure), and advanced symptoms like seizures. 1, 6
• One recent case report documented a patient on escitalopram and bupropion/naltrexone who developed both seizures and serotonin syndrome. 6

Cardiovascular monitoring is essential:

• Escitalopram can cause QT prolongation; do not exceed 40 mg/day (20 mg/day in adults >60 years). 5, 1
• Monitor baseline and periodic vital signs (blood pressure, heart rate) as both medications affect cardiovascular parameters. 2

Practical Dosing Algorithm

Starting regimen:

• Begin escitalopram at 10 mg once daily. 3
• Add bupropion at 150 mg once daily after 1 week. 2, 3

Titration schedule:

• Increase bupropion to 150 mg twice daily after 3-7 days if well tolerated. 2
• Escitalopram can be increased to maximum 20 mg/day by week 6. 3
• Bupropion maximum dose is 300 mg/day (not 400 mg as in some older studies). 2

Drug Interaction Considerations

Escitalopram is preferred over other SSRIs when combining with bupropion:

• Escitalopram has minimal effects on CYP450 enzymes, resulting in the lowest potential for drug interactions among SSRIs. 1, 2

Bupropion is a moderate-to-potent CYP2D6 inhibitor:

• Avoid or use caution with tamoxifen, as bupropion may reduce its efficacy. 2
• Consider interactions with other CYP2D6 substrates. 2

Avoid concurrent serotonergic medications (tramadol, triptans, MAO inhibitors) due to increased serotonin syndrome risk. 2

Monitoring Requirements

Baseline assessment:

• Blood pressure and heart rate. 2
• ECG if risk factors for QT prolongation exist. 5
• Screen for seizure history or predisposing conditions. 2

Ongoing monitoring:

• Neuropsychiatric effects including suicidality, particularly in adults 18-24 years (slightly increased risk). 5, 2
• Vital signs periodically throughout treatment. 2
• Signs of serotonin syndrome if other serotonergic agents are added. 1, 2

Special Populations

Pregnancy: Both medications have concerns—avoid this combination in pregnancy or active desire to become pregnant. 2

Older adults: Reduce escitalopram maximum dose to 20 mg/day in patients >60 years due to QT prolongation risk. 5, 1

Important Caveat on Efficacy

One randomized controlled trial found that combination therapy did not outperform monotherapy with either agent alone in terms of speed or rate of remission. 7 However, this contrasts with multiple open-label studies and clinical experience showing benefit, particularly for treatment-resistant depression and sexual side effect management. 3, 4 The combination remains widely used and guideline-supported despite this single negative trial. 2