What is the recommended dosing when combining Wellbutrin (bupropion) and Mirtazepine (mirtazapine)?

Dosing Recommendations for Combining Wellbutrin (Bupropion) and Mirtazapine

When combining bupropion (Wellbutrin) and mirtazapine (Remeron), the recommended dosing is bupropion 150 mg twice daily (maximum) and mirtazapine 7.5-30 mg at bedtime. 1

Initial Dosing and Titration

Bupropion (Wellbutrin)

• Starting dose: 37.5 mg every morning
• Titration: Increase by 37.5 mg every 3 days
• Target dose: 150 mg twice daily (maximum)
• Administration timing: Give second dose before 3 p.m. to minimize insomnia risk 1

Mirtazapine (Remeron)

• Starting dose: 7.5 mg at bedtime
• Target dose: 30 mg at bedtime (maximum)
• Administration timing: Always administer at bedtime to take advantage of sedative effects 1

Pharmacological Rationale for Combination

This combination leverages complementary mechanisms of action:

• Bupropion: Acts primarily on dopamine and norepinephrine neurotransmission with no appreciable serotonin activity 2

  • Activating effects (improves energy levels)
  • Rapid improvement in energy levels
  • No sexual dysfunction side effects

• Mirtazapine: Enhances both noradrenergic and serotonergic neurotransmission via blockade of central α2-adrenergic auto- and heteroreceptors 3

  • Promotes sleep and appetite
  • Sedating effects (beneficial at bedtime)
  • Weight gain potential

Monitoring and Titration Schedule

1. Week 1:

   • Bupropion 37.5 mg morning for 3 days, then increase to 75 mg morning
   • Mirtazapine 7.5 mg at bedtime

2. Week 2:

   • Bupropion 75 mg morning and 75 mg afternoon (before 3 p.m.)
   • Mirtazapine 15 mg at bedtime if 7.5 mg well-tolerated

3. Week 3-4:

   • Bupropion 150 mg morning and 150 mg afternoon (maximum dose)
   • Mirtazapine 15-30 mg at bedtime based on response and tolerability

4. Week 4-8: Assess full therapeutic response (full trial requires 4-8 weeks) 1

Important Precautions

Contraindications

• Seizure disorders (bupropion increases seizure risk) 1, 4
• Concurrent use of MAO inhibitors 4
• Patients with significant agitation (bupropion may worsen) 1

Side Effects to Monitor

• Bupropion: Insomnia, dry mouth, headache, agitation, tremor 2, 5
• Mirtazapine: Sedation, increased appetite, weight gain, dizziness 1, 3
• Combined therapy: Monitor for additive anticholinergic effects (dry mouth, constipation)

Drug Interactions

• Limited pharmacokinetic interactions between these specific agents have been reported
• Both medications are metabolized hepatically, so caution with other hepatically metabolized drugs 3

Efficacy Considerations

• The combination of antidepressants with complementary mechanisms may provide better outcomes than monotherapy for treatment-resistant depression 6
• A study comparing mirtazapine and paroxetine found that combination therapy produced greater improvement than monotherapy, with 43% remission rates for the combination versus 19-26% for monotherapy 6

Dosage Adjustments for Special Populations

• Hepatic/Renal Impairment: Reduce doses of both medications and titrate more slowly 3
• Elderly: Start with lower doses (bupropion 37.5 mg daily, mirtazapine 7.5 mg at bedtime) and titrate more gradually 1

Discontinuation

• After 9 months of successful treatment, consider gradual dose reduction to reassess need for medication 1
• Discontinue gradually over 10-14 days to limit withdrawal symptoms 1

This combination takes advantage of bupropion's activating properties and mirtazapine's sedating effects, potentially creating a balanced approach for patients with depression who need both daytime energy and nighttime sleep improvement.