What is the recommended dosage and precautions for using Wellbutrin (bupropion) and Trazodone together?

Dosage and Precautions for Using Wellbutrin (Bupropion) and Trazodone Together

The combination of Wellbutrin (bupropion) and trazodone is generally not recommended as a first-line treatment approach due to limited evidence supporting its efficacy and potential for adverse interactions, including the risk of serotonin syndrome.

Dosing Recommendations

If this combination must be used (such as for treatment-resistant depression or specific symptom profiles):

• Bupropion (Wellbutrin):

  • Starting dose: 100-150 mg once daily
  • Maintenance dose: 150 mg twice daily (SR) or 300 mg once daily (XL)
  • Maximum dose: 450 mg per day for immediate-release; 400 mg per day for sustained-release 1

• Trazodone:

  • Starting dose: 25-50 mg at bedtime
  • Therapeutic dose for insomnia: 50-100 mg at bedtime
  • Maximum dose: 400 mg per day in outpatients (divided doses); up to 600 mg in hospitalized patients 2, 3

Key Precautions

Risk of Serotonin Syndrome

• The combination can potentially cause serotonin syndrome, particularly when combined with other serotonergic agents or ECT 4, 5
• Symptoms include:
  • Altered mental status (confusion, agitation)
  • Neuromuscular abnormalities (myoclonus, hyperreflexia, tremor)
  • Autonomic instability (hyperthermia, tachycardia)
  • Gastrointestinal symptoms (nausea, vomiting, diarrhea)

Seizure Risk

• Bupropion carries a dose-dependent seizure risk of approximately 0.1% 1
• Risk factors include:
  • History of seizures or head trauma
  • CNS tumors
  • Eating disorders
  • Concomitant medications that lower seizure threshold
  • Abrupt discontinuation of alcohol or sedatives

Cardiovascular Considerations

• Trazodone may cause orthostatic hypotension and has been associated with cardiac arrhythmias in some patients with preexisting cardiac conditions 6
• Monitor blood pressure and heart rate, particularly when initiating or adjusting doses
• Use with caution in patients with preexisting ventricular irritability 6

Pharmacological Considerations

• Bupropion primarily affects dopamine and norepinephrine neurotransmission, with minimal effect on serotonin 3
• Trazodone is a serotonin antagonist and reuptake inhibitor with significant sedative properties 3
• The combination creates complementary effects:
  • Bupropion: activating, may cause insomnia, weight loss
  • Trazodone: sedating, may help with sleep, potential weight gain 7

Administration Guidelines

1. Timing:

   • Administer bupropion in the morning and early afternoon (before 3 PM) to minimize insomnia 1
   • Administer trazodone at bedtime to capitalize on its sedative effects 2

2. Titration:

   • Start with lower doses of both medications
   • Increase gradually at 5-7 day intervals to minimize side effects
   • Allow 4-6 weeks at therapeutic doses to evaluate efficacy 1, 3

3. Monitoring:

   • Weekly monitoring during initial titration
   • Assess for signs of serotonin syndrome, seizures, or cardiovascular effects
   • Evaluate therapeutic response after 4-6 weeks 1

Alternative Approaches

The American Academy of Sleep Medicine suggests that trazodone is not FDA approved for insomnia and its efficacy for this indication is not well established 2. Consider FDA-approved alternatives for insomnia if that is the primary reason for adding trazodone.

For depression, the American College of Physicians recommends modifying treatment if patients do not have an adequate response to pharmacotherapy within 6-8 weeks 1. Alternative augmentation strategies with better evidence may include:

• Mirtazapine (complementary to bupropion's mechanism)
• Aripiprazole or other atypical antipsychotics
• SNRIs like duloxetine

Special Populations

• Elderly: Use lower starting doses of both medications; increased risk of falls and orthostatic hypotension
• Pregnancy: Bupropion should be discontinued if pregnancy is planned or confirmed 1
• Hepatic impairment: Dose reduction may be necessary for both medications

Remember that this combination should be used with caution and only when the potential benefits outweigh the risks, with close monitoring for adverse effects.