Can Wellbutrin (bupropion) be added to augment a selective serotonin reuptake inhibitor (SSRI)?

Augmenting SSRIs with Bupropion (Wellbutrin) for Depression Treatment

Yes, bupropion (Wellbutrin) can effectively be added to augment an SSRI for patients with inadequate response to SSRI monotherapy, with evidence showing it decreases depression severity more than some other augmentation strategies. 1

Evidence for SSRI + Bupropion Combination

• Low-quality evidence from clinical trials shows that augmenting citalopram with bupropion decreases depression severity more effectively than augmentation with buspirone 1
• Moderate-quality evidence indicates that discontinuation due to adverse events is lower with bupropion than with buspirone when used as augmentation agents 1
• Open-label studies show approximately 54% of patients classified as responders when bupropion SR is added to SSRIs, demonstrating a decrease in depression rating scores of 50% or more 2

Advantages of Bupropion Augmentation

• Complementary mechanisms of action: Bupropion primarily affects dopamine and norepinephrine neurotransmission, while SSRIs target serotonin, providing a synergistic effect 3
• Addresses residual symptoms: Particularly effective for fatigue, low energy, and concentration difficulties that may persist despite SSRI treatment
• Sexual dysfunction management: Can help reduce SSRI-induced sexual side effects 4
• Minimal weight gain: Unlike some other augmentation strategies, bupropion is not associated with significant weight gain 5

Implementation Protocol

1. Patient selection:

   • Patients with partial response to adequate SSRI trial (typically 8-12 weeks at maximum tolerated dose)
   • Particularly suitable for patients with predominant symptoms of fatigue, anhedonia, or concentration difficulties
   • Consider for patients experiencing SSRI-induced sexual dysfunction

2. Dosing strategy:

   • Start with bupropion SR 150 mg once daily in the morning 3
   • After 3-7 days, may increase to 150 mg twice daily if tolerated
   • Maximum recommended dose is typically 300-400 mg/day when used as augmentation
   • Take morning dose before 3 PM to minimize insomnia risk 3

3. Monitoring requirements:

   • Assess for improvement in depression severity using standardized scales
   • Monitor for potential side effects: insomnia, agitation, dry mouth, headache
   • Evaluate blood pressure at baseline and periodically during treatment
   • Watch for rare but serious adverse effects including seizures (0.1% risk) 3

Precautions and Contraindications

• Seizure risk: Bupropion lowers seizure threshold; use with caution in patients with seizure history, head trauma, CNS tumors, or eating disorders 3
• Serotonin syndrome: Although rare with this combination, monitor for symptoms including agitation, hyperthermia, hyperreflexia, and incoordination 6
• Drug interactions: Bupropion inhibits CYP2D6, potentially increasing blood levels of certain SSRIs 6
• Avoid in patients with:
  • Current or prior diagnosis of bulimia or anorexia nervosa
  • Undergoing abrupt discontinuation of alcohol or sedatives
  • Taking MAO inhibitors (require 14-day washout)

Alternative Approaches if Bupropion Augmentation Fails

1. Switch to a different SSRI (moderate-quality evidence shows no difference in response when switching from one SGA to another) 1
2. Consider augmentation with an atypical antipsychotic (though this carries different side effect profile) 1
3. Consider switching to an SNRI like venlafaxine 1
4. Add cognitive behavioral therapy (low-quality evidence shows no difference in response or remission compared to medication switches) 1

Bupropion augmentation represents a well-tolerated, evidence-based approach for patients with inadequate response to SSRI monotherapy, with particular benefits for addressing specific residual symptoms and minimizing sexual side effects.