Can you mix Escitalopram and Bupropion (Wellbutrin)?

Combining Escitalopram and Bupropion

Yes, escitalopram and bupropion can be safely combined and this combination is commonly used in clinical practice for treating depression, particularly when patients have had an inadequate response to monotherapy or experience specific side effects. 1

Rationale for Combination

• Complementary mechanisms of action:

  • Escitalopram: Selective serotonin reuptake inhibitor (SSRI)
  • Bupropion: Norepinephrine-dopamine reuptake inhibitor

• Clinical benefits:

  1. Enhanced efficacy: The combination may help patients who have had partial response to either medication alone 2
  2. Reduced sexual dysfunction: Bupropion can counteract SSRI-induced sexual side effects 1, 3
  3. Improved energy and concentration: Bupropion is particularly helpful for patients with fatigue or low energy 1

Evidence for Safety and Efficacy

• A pilot study of 51 patients with chronic or recurrent depression treated with escitalopram and bupropion-SR showed:

  • 62% response rate and 50% remission rate
  • Only 6% discontinued due to side effects 2

• However, a later randomized controlled trial found that initial combination therapy with escitalopram and bupropion did not outperform monotherapy with either agent in terms of speed or rate of remission 4

Dosing Considerations

• Escitalopram: Start at 10 mg/day, can be titrated up to 20 mg/day
• Bupropion: Start at 150 mg/day, can be gradually increased to 300-400 mg/day
• In clinical studies, mean doses used were:
  • Escitalopram: 18 mg/day
  • Bupropion-SR: 327 mg/day 2

Potential Adverse Effects and Monitoring

• Common side effects:

  • Nausea, headache, insomnia, dry mouth, constipation
  • Sexual dysfunction (though less than with SSRI alone)
  • Increased blood pressure and heart rate

• Serious concerns:

  1. Seizure risk: Bupropion lowers seizure threshold; avoid in patients with seizure disorders 1
  2. Drug interactions: Bupropion inhibits CYP2D6, which could potentially affect escitalopram metabolism
  3. Rare case reports: One case of seizure-like symptoms in an infant exposed through breastfeeding 5

Contraindications

• Absolute contraindications:

  • Active seizure disorders
  • Current or prior diagnosis of bulimia or anorexia nervosa
  • Concurrent use of MAO inhibitors 6

• Use with caution in:

  • Patients with history of seizures
  • Patients with bipolar disorder (risk of triggering mania)
  • Pregnancy and breastfeeding

Monitoring Recommendations

1. Initial follow-up: 1-2 weeks after starting combination
2. Regular monitoring: Every 2-4 weeks until stable, then every 3 months
3. Parameters to assess:
   • Therapeutic response using standardized measures
   • Side effects, particularly insomnia and anxiety
   • Blood pressure and heart rate
   • Suicidal ideation, especially early in treatment 1

Clinical Pearls

• Start with lower doses of both medications and titrate gradually
• Consider this combination particularly for patients with:
  • SSRI-induced sexual dysfunction
  • Depression with prominent fatigue or concentration difficulties
  • Partial response to either medication alone
• Monitor closely for signs of increased anxiety, insomnia, or agitation
• The combination appears well-tolerated in most patients when properly dosed and monitored 3, 7

This combination represents a rational pharmacologic approach for many patients with depression, particularly those who haven't achieved full remission on monotherapy or who experience troublesome side effects from SSRIs alone.