What are the considerations for adding Bupropion (Wellbutrin) to Escitalopram (Lexapro) in treatment?

Adding Bupropion (Wellbutrin) to Escitalopram (Lexapro): Clinical Considerations

Adding bupropion to escitalopram is an effective strategy for patients with depression who have had an inadequate response to escitalopram monotherapy, experience sexual side effects, or have comorbid conditions that may benefit from this combination. 1, 2

Benefits of Adding Bupropion to Escitalopram

• Bupropion can enhance antidepressant response in patients who have had an inadequate response to escitalopram alone 2
• The combination can effectively address sexual dysfunction associated with SSRI treatment 2
• Bupropion has a different mechanism of action (affecting dopaminergic and noradrenergic systems) that complements escitalopram's serotonergic effects 3
• This combination may be particularly beneficial for patients with depression who are also attempting smoking cessation 1
• Bupropion may help counteract the common SSRI side effects of fatigue, sedation, and weight gain 1

Clinical Evidence Supporting the Combination

• Open-label studies have shown that combining bupropion with SSRIs like escitalopram can be effective for treatment-resistant depression 4, 3
• In one pilot study, the combination of escitalopram and bupropion-SR showed promising results with 50% of patients achieving remission 4
• The combination is generally well-tolerated with a low level of treatment-emergent adverse events 4

Important Considerations and Precautions

• Monitor vital signs regularly, especially blood pressure and heart rate, as bupropion can cause elevations in both 1
• Bupropion lowers the seizure threshold and should be avoided in patients with:
  • Seizure disorders
  • History of seizures
  • Clinical factors that increase seizure risk 1
• The combination should not be used in patients:
  • Taking monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOIs 1
  • With uncontrolled hypertension 1
  • Requiring opioid therapy (due to naltrexone component in some bupropion formulations) 1
• Monitor for neuropsychiatric adverse effects, including suicidal thoughts and behaviors, especially in individuals younger than 24 years 1

Dosing Recommendations

• Start with lower doses and titrate gradually:
  • Begin bupropion at 150 mg/day while maintaining the established dose of escitalopram 4
  • Gradually increase bupropion dose based on response and tolerability
  • Maximum recommended dose of bupropion is typically 400 mg/day when used in combination 4
• Allow 1-2 weeks between dose adjustments to assess response and side effects 1

Potential Side Effects to Monitor

• Common side effects include:
  • Nausea, headache, dry mouth, insomnia, constipation 1, 5
  • Increased blood pressure and heart rate 1
  • Anxiety or agitation 1
• Serious but rare side effects include:
  • Seizures (dose-dependent risk) 1
  • Neuropsychiatric symptoms including suicidal ideation 1
  • Hypertensive crisis (especially if combined with MAOIs) 1

Special Populations

• For older adults, start with lower doses and titrate more slowly 1
• Use with caution in patients with:
  • Cardiovascular disease
  • Hepatic or renal impairment
  • History of bipolar disorder (risk of triggering mania) 1

Monitoring Recommendations

• Assess therapeutic response within 1-2 weeks of initiating combination therapy 1
• Monitor blood pressure and heart rate periodically, especially in the first 12 weeks 1
• Evaluate for emergence of neuropsychiatric symptoms 1
• Reassess the need for continued combination therapy periodically 1