Can mirtazapine be administered with bupropion (Wellbutrin)?

Mirtazapine and Bupropion Combination Therapy for Depression

Mirtazapine can be safely and effectively administered with bupropion, offering complementary benefits for treating depression with potentially fewer side effects than either medication alone. 1

Rationale for Combination

The combination of mirtazapine and bupropion provides several therapeutic advantages:

• Complementary mechanisms of action:

  • Mirtazapine: Enhances norepinephrine and serotonin neurotransmission by blocking alpha-2 presynaptic adrenoceptors and antagonizes 5-HT2, 5-HT3, and H1 receptors 1, 2
  • Bupropion: Acts on norepinephrine and dopamine neurotransmitters with no appreciable activity on serotonin 2

• Enhanced efficacy: Combination therapy with mirtazapine and bupropion may double the likelihood of remission compared to monotherapy 1, 3

• Counterbalancing side effects:

  • Bupropion's activating properties can help offset mirtazapine's sedation 1
  • Mirtazapine's appetite-stimulating effects may balance bupropion's potential appetite suppression 2, 4

Dosing Recommendations

• Mirtazapine:

  • Starting dose: 7.5-15 mg at bedtime
  • Can be titrated to 30-45 mg daily
  • Effective dose range: 15-45 mg once daily 1, 4

• Bupropion:

  • Starting dose: 37.5-150 mg in the morning
  • Can be titrated to 150 mg twice daily
  • Second dose should be administered before 3 PM to minimize insomnia risk
  • Maximum doses: 450 mg/day (immediate-release) or 400 mg/day (sustained-release) 1, 2

Clinical Benefits of This Combination

1. Improved remission rates:

   • Studies show combination therapy may achieve remission rates of 46% compared to 25% with SSRI monotherapy 3

2. Reduced side effect burden:

   • Lower rates of sexual dysfunction compared to SSRIs 1
   • Morning dosing of bupropion and evening dosing of mirtazapine optimizes complementary effects 1

3. Particularly useful for specific symptom profiles:

   • Depression with insomnia (mirtazapine's sedative effects)
   • Poor appetite (mirtazapine increases appetite)
   • Fatigue (bupropion's activating effects)
   • Sexual dysfunction (bupropion has lower rates of sexual side effects) 1, 5

Potential Concerns and Management

• Seizure risk with bupropion:

  • Gradually titrate bupropion dose
  • Avoid in patients with seizure disorders 2

• Sedation with mirtazapine:

  • Administer at bedtime
  • Bupropion's activating effects may help counterbalance this side effect 1, 2

• Weight considerations:

  • Mirtazapine may increase appetite and weight
  • Bupropion may partially offset this effect 2, 4

• Restless legs syndrome:

  • If RLS develops with mirtazapine, bupropion may actually help resolve this side effect 6

Monitoring Recommendations

• Assess response within 1-2 weeks (early improvements may be seen)
• Full therapeutic effect typically observed at 4-6 weeks 2
• Monitor for:
  • Changes in sleep patterns
  • Appetite and weight changes
  • Sexual function
  • Mood and energy levels

Clinical Pearl

The combination of mirtazapine and bupropion represents a rational pharmacological approach that targets multiple neurotransmitter systems (serotonin, norepinephrine, and dopamine) while potentially minimizing side effects that might occur with either agent alone 1, 5. This combination may be particularly valuable for patients who have not responded adequately to monotherapy or who experience troublesome side effects with single agents.