Can You Add Lexapro 5mg to Wellbutrin SR 150mg BID?
Yes, you can safely add Lexapro (escitalopram) 5mg to Wellbutrin SR (bupropion) 150mg twice daily—this combination is commonly used, well-tolerated, and effective for treatment-resistant depression. 1
Evidence Supporting the Combination
The combination of an SSRI (like escitalopram) with bupropion is a well-established strategy in clinical practice:
A pilot study specifically evaluated escitalopram combined with bupropion-SR in 51 outpatients with chronic or recurrent major depressive disorder, demonstrating a 62% response rate and 50% remission rate—significantly higher than typical SSRI monotherapy. 1
The combination was well-tolerated with only 6% of patients discontinuing due to side effects, and the mean doses achieved were escitalopram 18mg/day and bupropion-SR 327mg/day. 1
Combinations of SSRIs and bupropion can convert partial response to full response in patients with treatment-resistant depression. 2
Safety Considerations
Serotonin Syndrome Risk (Low but Monitor)
While combining two serotonergic agents theoretically increases risk, the actual clinical risk is manageable:
Exercise caution when combining two or more non-MAOI serotonergic drugs, starting the second agent at a low dose and increasing slowly, with monitoring especially in the first 24-48 hours after dosage changes. 3
Escitalopram/citalopram has the least effect on CYP450 isoenzymes compared with other SSRIs and thus has a lower propensity for drug interactions. 3
Bupropion is a dopamine/norepinephrine reuptake inhibitor (not primarily serotonergic), which reduces the theoretical risk of serotonin syndrome when combined with an SSRI. 3
Practical Monitoring
Monitor for serotonin syndrome symptoms: mental status changes (confusion, agitation, anxiety), neuromuscular hyperactivity (tremors, clonus, hyperreflexia), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis). 3
Assess patient status, therapeutic response, and adverse effects within 1-2 weeks of initiating the combination therapy. 3
Dosing Strategy
Your proposed starting dose is appropriate:
Starting escitalopram at 5mg is conservative and reasonable, as this is below the typical starting dose of 10mg/day. 3
The patient's current bupropion SR 150mg BID (300mg total daily) is at the maximum recommended dose and should not be increased further. 3
If needed, escitalopram can be titrated up to 10-20mg daily based on response, with dose increases every 1-2 weeks. 3
Common Pitfalls to Avoid
Do not combine with MAOIs—this is absolutely contraindicated due to severe serotonin syndrome risk. 3
Be aware that bupropion can cause dose-related adverse effects including insomnia (give second dose before 3 PM), agitation, and rarely dystonia at higher doses. 3, 4
SSRIs commonly cause sexual dysfunction, but bupropion may actually counteract this side effect—a therapeutic advantage of this combination. 5
Monitor for increased suicidal thoughts/behaviors, particularly in the first 1-2 months of treatment, as SSRIs carry this FDA warning. 3