Can patients take trazodone and Wellbutrin (bupropion) together?

Trazodone and Bupropion Combination Safety and Efficacy

Yes, patients can take trazodone and bupropion (Wellbutrin) together, but this combination requires monitoring for potential serotonin syndrome, especially when initiating therapy or changing doses.

Mechanism and Rationale for Combination

• Trazodone is a serotonin antagonist and reuptake inhibitor (SARI) primarily used off-label for insomnia at lower doses (50-150mg), while at higher doses (150-400mg) it functions as an antidepressant 1
• Bupropion (Wellbutrin) uniquely targets norepinephrine and dopamine neurotransmitters with no significant serotonergic activity 2
• The combination may be beneficial as it:
  • Targets multiple neurotransmitter systems (serotonin via trazodone; norepinephrine/dopamine via bupropion)
  • Addresses both depression and insomnia simultaneously
  • May minimize side effects compared to higher doses of either agent alone 1

Clinical Evidence Supporting Combination

• Clinical experience suggests the general safety and efficacy of combining medications from different antidepressant classes 1
• Combination therapy may improve efficacy by targeting multiple sleep-wake mechanisms while minimizing toxicity that could occur with higher doses of a single agent 1
• Bupropion is often combined with other antidepressants due to its complementary mechanism of action 2

Potential Risks and Monitoring

Serotonin Syndrome Risk

• While rare, case reports document serotonin syndrome with this combination, particularly when combined with other factors like electroconvulsive therapy 3
• The risk appears lower than with SSRI combinations, as bupropion has minimal direct serotonergic activity 4

Drug Interactions

• Bupropion and its metabolites inhibit CYP2D6, which could potentially affect trazodone metabolism, though this specific interaction is not well-documented 5
• Both medications can lower seizure threshold, so caution is needed in patients with seizure disorders 5

Side Effect Profile

• Common side effects to monitor:
  • Sedation (primarily from trazodone)
  • Insomnia, agitation, dry mouth (primarily from bupropion)
  • Dizziness, headache (both medications)
  • Sexual dysfunction (less common than with SSRIs) 2

Dosing Considerations

• Start with low doses of both medications and titrate gradually:
  • Trazodone: Often started at 50-100mg at bedtime for sleep
  • Bupropion: Initial dose of 150mg once daily, gradually increasing if needed 2
• Maximum recommended doses:
  • Trazodone: 400mg daily for outpatients (600mg for inpatients under supervision) 2
  • Bupropion: 450mg daily (immediate-release) or 400mg daily (sustained-release) 2

Contraindications

• Absolute contraindications:
  • Concurrent use of MAO inhibitors (must allow 14-day washout period) 5
  • Seizure disorders (relative contraindication for bupropion) 5
  • Pregnancy or attempting to conceive 1

Clinical Decision Algorithm

1. Assess need: Determine if combination is appropriate (e.g., depression with insomnia)
2. Screen for contraindications: Seizure history, MAOIs use, pregnancy
3. Start low: Begin with lowest effective doses of both medications
4. Monitor closely: Watch for signs of serotonin syndrome (confusion, agitation, muscle rigidity, hyperthermia) especially in first few weeks
5. Titrate gradually: Increase doses based on response and tolerability
6. Reassess regularly: Evaluate ongoing need for combination therapy

Bottom Line

The combination of trazodone and bupropion can be effective and relatively safe when properly monitored, particularly for patients with depression and insomnia. The complementary mechanisms of action may provide better symptom control than monotherapy while potentially reducing side effects associated with higher doses of either medication alone.