What is the dose regimen for using mirtazapine with Wellbutrin (bupropion)?

Mirtazapine and Bupropion (Wellbutrin) Combination: Dosing Regimen

The recommended dosing regimen for using mirtazapine with bupropion (Wellbutrin) is to start with mirtazapine 7.5 mg at bedtime and bupropion 37.5 mg every morning, then gradually titrate to effective doses of mirtazapine 15-30 mg at bedtime and bupropion up to 150 mg twice daily. 1

Indications for Combination Therapy

This combination can be particularly beneficial for patients with:

• Depression with sleep disturbances (mirtazapine promotes sleep)
• Depression with fatigue or apathy (bupropion is activating)
• Depression with appetite/weight loss (mirtazapine increases appetite)
• Depression with anxiety symptoms

Dosing Algorithm

Mirtazapine Dosing:

• Initial dose: 7.5 mg at bedtime 1
• Titration: Increase to 15 mg at bedtime after 1 week
• Maximum dose: 30 mg at bedtime 1
• Timing: Always administer at bedtime to take advantage of sedative effects

Bupropion Dosing:

• Initial dose: 37.5 mg every morning 1
• Titration: Increase by 37.5 mg every 3 days as tolerated
• Maximum dose: 150 mg twice daily 1
• Timing: Morning dose and second dose before 3 PM to minimize insomnia risk

Pharmacological Rationale

This combination works well because:

1. Complementary mechanisms of action:

   • Mirtazapine: Noradrenergic and specific serotonergic antidepressant (NaSSA) that blocks α2-adrenergic receptors and 5-HT2/5-HT3 receptors 2
   • Bupropion: Norepinephrine-dopamine reuptake inhibitor with no significant serotonergic activity 2

2. Complementary side effect profiles:

   • Mirtazapine's sedative effects can counterbalance bupropion's activating properties
   • Bupropion's weight-neutral or weight-loss effects can offset mirtazapine's tendency to increase appetite and weight 2, 3

Monitoring Parameters

• First 4-8 weeks: Weekly monitoring for therapeutic response and side effects
• After stabilization: Monthly monitoring
• Key parameters to monitor:
  • Sleep quality
  • Energy levels
  • Appetite/weight changes
  • Vital signs (particularly blood pressure and heart rate)
  • Emergence of anxiety or agitation

Important Precautions

• Seizure risk: Bupropion lowers seizure threshold; use with caution in patients with seizure disorders 1
• Insomnia risk: To minimize insomnia with bupropion, administer the second dose before 3 PM 1
• Agitation: Bupropion should not be used in agitated patients 1
• Therapeutic trial duration: A full therapeutic trial requires at least 4-8 weeks 1
• Discontinuation: When discontinuing either medication, taper over 10-14 days to limit withdrawal symptoms 1

Clinical Pearls

• The sedative effects of mirtazapine are actually more pronounced at lower doses (7.5-15 mg) than at higher doses due to greater H1 receptor antagonism at lower concentrations 3, 4
• Despite common belief, higher doses of mirtazapine do not appear to significantly increase noradrenergic side effects like tachycardia or anxiety 4
• Bupropion may provide rapid improvement in energy levels, which can be beneficial early in treatment 1
• Mirtazapine has a long half-life (20-40 hours), making it suitable for once-daily dosing 3

This combination leverages the unique properties of both medications to potentially address multiple symptoms of depression while minimizing the side effects that might occur with higher doses of either medication alone.