Can Wellbutrin (bupropion) be added to Prozac (fluoxetine) 60mg in patients with inadequate response?

Adding Wellbutrin to Prozac 60mg for Inadequate Response

Wellbutrin (bupropion) can be effectively added to Prozac (fluoxetine) 60mg as an augmentation strategy for patients with inadequate response to antidepressant monotherapy. 1, 2

Rationale for Combination Therapy

• The American College of Physicians recommends modifying treatment if patients do not have an adequate response to pharmacotherapy within 6-8 weeks of initiation 1
• Multiple pharmacologic therapies may be required for patients who do not respond to first-line treatments 1
• Bupropion and fluoxetine have complementary mechanisms of action:
  • Fluoxetine primarily affects serotonin
  • Bupropion affects dopamine and norepinephrine 2, 3

Dosing and Administration

• Start bupropion at a low dose and titrate gradually:
  • Begin with 150mg once daily (morning) for 3-4 days
  • Increase to 150mg twice daily (maximum 400mg/day) 2, 4
  • Take second dose before 3pm to minimize insomnia risk 2
• Continue fluoxetine at current dose (60mg)
• Allow 4-6 weeks at optimal doses to evaluate full response 1, 4

Benefits of This Combination

• Improved efficacy: 50-60% of patients with inadequate SSRI response may benefit from bupropion augmentation 3, 5
• Complementary side effect profiles:
  • Bupropion may counteract SSRI-induced sexual dysfunction 3, 6
  • Bupropion's activating properties may help with residual fatigue/apathy 2, 6
• Lower risk of weight gain compared to some other augmentation strategies 6

Monitoring and Precautions

• Monitor closely for:
  • Blood pressure and heart rate increases (both medications can affect these) 2
  • Increased anxiety or agitation (particularly in first 1-2 weeks) 2
  • Seizure risk (bupropion lowers seizure threshold, 0.1% risk) 2
  • Suicidal thoughts/behaviors (especially in first 1-2 months) 1

Important Contraindications

• History of seizure disorder
• Current or prior diagnosis of bulimia or anorexia nervosa
• Use of MAO inhibitors within 14 days
• Abrupt discontinuation of alcohol or benzodiazepines 2, 6

If Inadequate Response

• If no significant improvement after 6-8 weeks of combination therapy:
  • Consider switching to a different antidepressant class
  • Consider other augmentation strategies (antipsychotics, mood stabilizers)
  • Evaluate for treatment-resistant depression requiring specialized approaches 1, 2

This combination approach is supported by both clinical guidelines and research evidence showing that bupropion augmentation can boost antidepressant response in patients with inadequate response to SSRI monotherapy.