Can Wellbutrin (bupropion), Buspar (buspirone), and Remeron (mirtazapine) be given together?

Concurrent Use of Wellbutrin, Buspar, and Remeron

Wellbutrin (bupropion), Buspar (buspirone), and Remeron (mirtazapine) can be safely administered together, though careful monitoring is required due to their unique mechanisms of action and potential for side effects.

Pharmacological Considerations

Individual Medication Profiles

1. Wellbutrin (Bupropion)

   • Unique antidepressant with no appreciable activity on serotonin; acts primarily on norepinephrine and dopamine neurotransmitters 1
   • Common side effects: agitation, insomnia, headaches, dry mouth, tremor
   • Most serious side effect: seizures (dose-dependent risk of approximately 0.1%) 2
   • Typical dosing: 150-450 mg daily (immediate-release) or 150-400 mg daily (sustained-release) 1

2. Buspar (Buspirone)

   • Anxiolytic that enhances serotonergic activity through 5-HT1A receptor partial agonism
   • Common side effects: dizziness, headache, nervousness, lightheadedness
   • Typical dosing: 15-45 mg daily divided into multiple doses 2

3. Remeron (Mirtazapine)

   • Enhances norepinephrine and serotonin neurotransmission by blocking alpha-2 presynaptic adrenoceptors
   • Also binds to 5-HT2, 5-HT3, and H1 receptors
   • Common side effects: sedation, increased appetite, weight gain, dizziness
   • Typical dosing: 7.5-45 mg once daily at bedtime 2, 1

Safety of Combination Therapy

The combination of these three medications can be used together with appropriate monitoring as:

1. Each medication has a distinct mechanism of action that can potentially provide complementary effects:

   • Bupropion primarily affects dopamine and norepinephrine
   • Buspirone acts as a 5-HT1A partial agonist
   • Mirtazapine affects multiple receptors including alpha-2 adrenergic and serotonin receptors

2. There are no absolute contraindications to using these medications together in the available guidelines 3, 2

3. Case reports and clinical experience have demonstrated that combinations of antidepressants with different mechanisms of action can be effective for treatment-resistant depression 4, 5

Potential Concerns and Monitoring

When using this combination, be aware of:

1. Seizure risk: Bupropion carries a dose-dependent seizure risk. Start with lower doses and titrate gradually 2, 1

2. Potential for drug interactions:

   • Bupropion is metabolized by CYP2B6
   • Mirtazapine is metabolized by CYP1A2, CYP2D6, and CYP3A4
   • Monitor for potential pharmacokinetic interactions

3. Additive side effects:

   • Sedation from mirtazapine may offset insomnia from bupropion
   • Potential for additive CNS effects
   • Risk of movement disorders (rare but reported with bupropion) 6

4. Serotonin syndrome risk:

   • While the risk is lower than with SSRIs, the combination of buspirone and mirtazapine theoretically increases this risk
   • Monitor for symptoms like agitation, hyperthermia, hyperreflexia, and incoordination

Dosing Recommendations

When initiating this combination:

1. Start with lower doses of each medication and titrate gradually:

   • Bupropion: Start at 150 mg once daily, with the second daily dose before 3 p.m. to minimize insomnia risk 2
   • Mirtazapine: Start at 7.5 mg at bedtime, titrating to a maximum of 30 mg 2
   • Buspirone: Start at lower doses and titrate to 15 mg three times daily as needed 7

2. Space the medications throughout the day to minimize peak concentration overlaps:

   • Mirtazapine at bedtime (leveraging sedative effects)
   • Bupropion in the morning (to minimize insomnia)
   • Buspirone divided throughout the day

Evidence for Efficacy

While there are no specific studies examining the exact three-drug combination:

1. Buspirone augmentation of antidepressants has been studied, though with mixed results 7

2. Bupropion has been successfully combined with serotonergic antidepressants in treatment-resistant depression 4

3. Mirtazapine's unique receptor profile makes it a rational choice for combination therapy due to its complementary mechanism of action 1

Conclusion

This three-medication combination can be used together with appropriate monitoring and dose adjustments. The distinct mechanisms of action may provide complementary benefits, particularly in treatment-resistant cases. Start with lower doses, monitor closely for side effects, and adjust based on individual response and tolerability.