Can mirtazapine be administered with bupropion (Wellbutrin)?

Mirtazapine and Bupropion Combination Therapy in Depression

Yes, mirtazapine can be safely administered with bupropion, and this combination may offer complementary benefits for treating depression with potentially fewer side effects than either medication alone. 1, 2

Pharmacological Rationale for Combination

Mirtazapine and bupropion have distinct and complementary mechanisms of action:

• Mirtazapine: Acts as an alpha-2 adrenergic antagonist and blocks 5-HT2 and 5-HT3 receptors, enhancing norepinephrine and serotonin neurotransmission 3
• Bupropion: Inhibits norepinephrine and dopamine reuptake with no appreciable effect on serotonin 3

This combination provides a multi-neurotransmitter approach targeting serotonin, norepinephrine, and dopamine systems.

Clinical Evidence Supporting Combination

Research demonstrates that combining mirtazapine with other antidepressants, including bupropion, can be beneficial:

• A double-blind randomized study showed that mirtazapine combined with bupropion achieved a 46% remission rate compared to 25% with fluoxetine monotherapy 4
• The combination may reduce the latency of antidepressant response and enhance overall efficacy 5

Advantages of This Combination

1. Complementary side effect profiles:

   • Bupropion is activating and can counterbalance mirtazapine's sedative effects 1, 3
   • Mirtazapine promotes sleep, appetite, and weight gain, while bupropion is less likely to cause these effects 1

2. Sexual function benefits:

   • Bupropion has significantly lower rates of sexual adverse events compared to SSRIs 1, 2
   • Can be particularly beneficial for patients concerned about sexual dysfunction 2

3. Potential for improved efficacy:

   • Combination therapy from treatment initiation may double the likelihood of remission compared to monotherapy 4

Dosing Considerations

• Mirtazapine: Start with 7.5-15 mg at bedtime, can be titrated up to 30-45 mg daily 1, 3
• Bupropion: Start with 37.5-150 mg in the morning, can be titrated up to 150 mg twice daily 1
• To minimize insomnia risk, administer the second dose of bupropion before 3 PM 1

Monitoring and Precautions

1. Safety considerations:

   • No specific warnings against this combination in guidelines or drug labels 1
   • No significant drug interactions have been reported between these medications 3, 6

2. Potential adverse effects to monitor:

   • Mirtazapine: Sedation, increased appetite, weight gain 3, 6
   • Bupropion: Insomnia, dry mouth, headache, seizure risk (dose-dependent) 3
   • Monitor for changes in blood pressure and heart rate

3. Special situations:

   • In one case report, bupropion actually resolved restless legs syndrome associated with mirtazapine use 7

Clinical Pearls

• This combination may be particularly useful for patients with depression accompanied by insomnia, poor appetite, or sexual dysfunction
• The activating properties of bupropion can help counteract the sedation commonly experienced with mirtazapine
• Consider starting with lower doses of both medications and titrating gradually to minimize side effects
• Morning dosing of bupropion and evening dosing of mirtazapine can optimize the complementary effects

The evidence supports that mirtazapine and bupropion can be safely and effectively combined, potentially offering better efficacy and a more favorable side effect profile than either medication alone.