Can mirtazapine and bupropion be prescribed together?

Prescribing Mirtazapine and Bupropion Together

Yes, mirtazapine and bupropion can be safely prescribed together and may provide complementary benefits due to their different mechanisms of action. 1, 2

Pharmacological Rationale

• Mirtazapine: Works as an alpha-2 adrenergic antagonist that enhances norepinephrine and serotonin neurotransmission, with additional antagonist effects at 5-HT2, 5-HT3, and H1 receptors 2

  • Initial dose: 7.5 mg at bedtime
  • Maximum dose: 30 mg at bedtime
  • Promotes sleep, appetite, and weight gain 1

• Bupropion: Acts as a norepinephrine and dopamine reuptake inhibitor with no serotonergic activity 2

  • Initial dose: 37.5 mg every morning, then increase by 37.5 mg every 3 days
  • Maximum dose: 150 mg twice daily
  • Activating, may rapidly improve energy levels 1

Benefits of Combination

1. Complementary mechanisms: Mirtazapine affects serotonin and norepinephrine systems while bupropion affects dopamine and norepinephrine systems, potentially addressing a broader range of symptoms 2

2. Counterbalancing side effects:

   • Mirtazapine's sedating effects may balance bupropion's activating properties 1, 2
   • Bupropion's tendency to decrease appetite may offset mirtazapine's appetite-stimulating and weight gain effects 1

3. Improved efficacy: Research suggests combination antidepressant therapy from treatment initiation may double the likelihood of remission compared to monotherapy 3

Clinical Considerations

Dosing Strategy

• Start with lower doses of each medication
• For mirtazapine: Begin with 7.5-15 mg at bedtime
• For bupropion: Begin with 37.5-75 mg in the morning
• Titrate doses gradually based on response and tolerability
• To minimize insomnia risk, administer the second dose of bupropion before 3 PM 1

Monitoring Parameters

• Sleep patterns: Watch for insomnia (from bupropion) or excessive sedation (from mirtazapine)
• Appetite and weight: Monitor for significant changes in either direction
• Blood pressure and heart rate: Both medications can affect cardiovascular parameters
• Seizure risk: Bupropion lowers seizure threshold; maximum dose should not exceed 150 mg twice daily 1

Potential Adverse Effects

• Common side effects:
  • Bupropion: Insomnia, dry mouth, headache, nausea, tremor 2
  • Mirtazapine: Sedation, increased appetite, weight gain, dizziness 2
• Serious concerns:
  • Seizure risk with bupropion, especially at higher doses 1
  • Potential for transient elevations in liver function tests with mirtazapine 2

Special Populations and Contraindications

• Avoid in patients with:

  • Seizure disorders (bupropion contraindicated) 1
  • Concurrent use of MAO inhibitors (requires 14-day washout period) 4
  • Patients on opioids (may reduce efficacy) 4

• Use with caution in:

  • Elderly patients (start with lower doses of both medications)
  • Patients with liver or kidney dysfunction 4
  • Patients with cardiovascular disease 4

Practical Implementation

1. Begin with lower doses of both medications
2. Schedule bupropion in the morning and mirtazapine at bedtime to optimize the activating and sedating effects, respectively
3. Gradually increase doses based on clinical response and tolerability
4. Monitor for improvement in both mood and energy levels
5. If discontinuation is needed, taper gradually to minimize withdrawal symptoms 4

This combination can be particularly beneficial for patients with depression characterized by both low mood and fatigue/lack of motivation, as it addresses multiple neurotransmitter systems involved in depression pathophysiology.