Combining Wellbutrin and Lexapro: Safety and Efficacy
Yes, combining Wellbutrin (bupropion) and Lexapro (escitalopram) is safe and represents a recognized treatment strategy for depression, particularly when used as augmentation therapy after inadequate response to monotherapy. 1
Evidence Supporting Safety
The American College of Physicians recognizes this combination as a legitimate treatment approach, with both medications working through different mechanisms—bupropion affects dopaminergic and noradrenergic systems while escitalopram is a selective serotonin reuptake inhibitor (SSRI). 1
Moderate-quality evidence demonstrates that discontinuation due to adverse events was actually lower with bupropion augmentation compared to buspirone augmentation, indicating a favorable safety profile. 2, 1
Low-quality evidence shows no difference in serious adverse events or suicidal ideation when augmenting SSRIs with bupropion. 2
Clinical Advantages of This Combination
Bupropion has a lower risk of sexual side effects compared to other antidepressants, which can counteract the sexual dysfunction commonly associated with SSRIs like escitalopram. 1
Open-label studies show response rates of 62% and remission rates of 50% with this combination, substantially higher than typical SSRI monotherapy. 3
The combination was well-tolerated in clinical trials, with only 6% of patients discontinuing due to side effects. 3
Efficacy Considerations
However, the highest quality randomized controlled trial (2014) did not demonstrate that starting both medications together outperformed monotherapy in either speed of remission or overall remission rates. 4
This suggests the combination is most appropriate as augmentation therapy rather than initial treatment. 1
When used as augmentation of citalopram (a closely related SSRI to escitalopram), bupropion decreased depression severity more than buspirone augmentation. 2
Critical Safety Monitoring
Both medications can potentially lower the seizure threshold, though this is primarily a concern with bupropion at higher doses. 1
Bupropion is contraindicated in patients with seizure risks, including those with history of stroke or brain metastases. 1
Neither medication should be combined with MAOIs due to risk of hypertensive crisis or serotonin syndrome. 1
Monitor for neuropsychiatric symptoms, though recent large trials have not shown significant increases in these events. 1
Recommended Dosing Strategy
Start with escitalopram 10 mg daily as monotherapy first, then add bupropion 150 mg daily if there is partial response after an adequate trial (typically 4-8 weeks). 1
- Maximum dose of escitalopram: 20 mg daily 3
- Maximum dose of bupropion: 300-400 mg daily (divided dosing for immediate release, once or twice daily for sustained release) 3
- Mean effective doses in clinical studies: escitalopram 18 mg/day and bupropion-SR 327 mg/day 3
Clinical Algorithm
Initiate monotherapy with either escitalopram or bupropion based on patient-specific factors (sexual dysfunction concerns favor bupropion; anxiety comorbidity favors escitalopram). 1
Assess response after 4-8 weeks at therapeutic doses. 1
If partial response, add the second agent rather than switching. 1
Titrate the second medication over 1-2 weeks while maintaining the first agent at therapeutic dose. 3
Monitor closely for side effects during the first 2-4 weeks of combination therapy, particularly insomnia, tremor, and activation. 3, 5
Common Pitfalls to Avoid
Do not start both medications simultaneously as initial treatment—evidence does not support superior outcomes compared to monotherapy, and it complicates identification of which medication causes side effects. 4
Do not use inadequate doses—ensure each medication reaches therapeutic levels before concluding the combination is ineffective. 3
Do not overlook sexual dysfunction from the SSRI—this is where bupropion augmentation provides particular benefit. 1
Do not exceed bupropion 450 mg/day due to dose-dependent seizure risk. 1