Is it safe to combine Wellbutrin (bupropion) and Lexapro (escitalopram)?

Safety of Combining Wellbutrin (Bupropion) and Lexapro (Escitalopram)

Yes, combining Wellbutrin (bupropion) and Lexapro (escitalopram) is generally safe and can be an effective treatment strategy for depression. 1

Evidence for Safety and Efficacy

• Bupropion and escitalopram have different mechanisms of action, with bupropion affecting dopaminergic and noradrenergic systems while escitalopram is a selective serotonin reuptake inhibitor (SSRI) 1
• Clinical guidelines indicate that augmenting an SSRI (like escitalopram) with bupropion is a recognized treatment strategy for patients with depression 1
• Low-quality evidence from clinical trials shows that augmenting citalopram (similar to escitalopram) with bupropion can decrease depression severity more than augmentation with buspirone 1
• Moderate-quality evidence indicates that discontinuation due to adverse events was actually lower with bupropion than with buspirone when used as augmentation therapy 1

Advantages of This Combination

• Bupropion has a lower risk of sexual side effects compared to other antidepressants, which can help counteract the sexual dysfunction commonly associated with SSRIs like Lexapro 1
• The combination may provide more comprehensive neurotransmitter coverage by targeting both serotonergic (escitalopram) and dopaminergic/noradrenergic (bupropion) systems 2
• For treatment-resistant depression, combination therapy may be more effective than monotherapy in some cases 3

Potential Concerns and Monitoring

• Both medications can potentially lower the seizure threshold, though this is primarily a concern with bupropion at higher doses 1
• Bupropion is contraindicated for patients with seizure risks (stroke, brain metastases) 1
• While rare, there have been case reports of adverse events in special populations (such as an infant exposed through breastfeeding) when both medications were used together 4
• Careful monitoring for neuropsychiatric symptoms is recommended, although recent large trials have not shown significant increases in these events with either medication 1

Dosing Considerations

• When used in combination therapy, standard dosing can be maintained:
  • Bupropion: Usually 150-300 mg daily 1
  • Escitalopram: Usually 10-20 mg daily 1
• Dose adjustments may be needed based on individual response and tolerability 1

Drug Interaction Considerations

• The combination does not have major pharmacokinetic interactions that would significantly alter blood levels of either medication 5
• The risk of serotonin syndrome is lower with this combination compared to combining multiple serotonergic agents 5
• Neither medication should be combined with MAOIs due to risk of hypertensive crisis or serotonin syndrome 1, 5

Clinical Decision Algorithm

1. Start with either escitalopram or bupropion as monotherapy first
2. If partial response after adequate trial (4-6 weeks), consider adding the second agent
3. Monitor closely for side effects during the first few weeks of combination therapy
4. Assess for improvement in depressive symptoms and any emerging side effects
5. If both medications are well-tolerated but response remains inadequate, consider alternative strategies 1

This combination is supported by clinical guidelines and can be particularly helpful for patients who have had an inadequate response to SSRI monotherapy or who experience problematic side effects (particularly sexual dysfunction) with SSRIs alone 1, 3.