How to switch from 45mg mirtazapine (Remeron) to trazodone (Serotonin Antagonist and Reuptake Inhibitor, SARI)?

Switching from 45mg Mirtazapine to Trazodone

A gradual cross-tapering approach is recommended when switching from 45mg mirtazapine to trazodone to minimize withdrawal symptoms and maintain therapeutic efficacy. 1

Recommended Cross-Tapering Schedule

1. Week 1:

   • Reduce mirtazapine from 45mg to 30mg daily
   • Start trazodone at 50mg at bedtime

2. Week 2:

   • Reduce mirtazapine to 15mg daily
   • Increase trazodone to 100mg at bedtime

3. Week 3:

   • Discontinue mirtazapine
   • Titrate trazodone to target dose (typically 150-300mg for depression or 50-100mg for insomnia)

Pharmacological Considerations

• Mirtazapine has a half-life of 20-40 hours, allowing for a gradual taper 2
• At 45mg daily, plasma concentrations of mirtazapine are approximately 28±12 ng/mL 3
• Trazodone has a shorter half-life and works through different mechanisms:
  • Functions as a 5-HT2A/5-HT2C receptor antagonist and serotonin reuptake inhibitor 1
  • At 150mg daily, plasma concentrations reach approximately 624-680 ng/mL 3

Monitoring During Transition

• First 7-10 days: Monitor closely for withdrawal symptoms from mirtazapine (irritability, anxiety, sleep disturbances) and side effects from trazodone (sedation, dizziness, dry mouth)
• Sedation management: Since both medications can cause sedation, administer both doses at bedtime during the cross-tapering period
• Cardiovascular effects: Monitor for QT prolongation with trazodone, especially in patients with pre-existing cardiac conditions 1

Dosage Considerations

• For insomnia treatment: Target trazodone dose is typically 50-100mg at bedtime
• For depression treatment: Target trazodone dose is typically 150-300mg daily (maximum outpatient dose: 400mg daily) 4
• Therapeutic response timing: One-third of inpatients and half of outpatients show significant therapeutic response to trazodone by the end of the first week, with others responding within 2-4 weeks 4

Important Precautions

• Risk of serotonin syndrome: While the risk is low during cross-tapering of these specific medications, be alert for symptoms (agitation, tremor, hyperthermia)
• Cardiac patients: Use trazodone with caution due to potential for QT prolongation 1
• Bipolar disorder: Both medications have low risk for switch to mania when used at lower doses, particularly when used for sleep promotion 5

Follow-up Recommendations

• Schedule follow-up within 7-10 days of initiating the switch to assess tolerability and efficacy
• Use standardized measures like the Insomnia Severity Index (ISI) if treating insomnia, or depression rating scales if treating depression
• Adjust the trazodone dose based on therapeutic response and side effects

This cross-tapering approach minimizes the risk of withdrawal symptoms while allowing for assessment of trazodone's efficacy and tolerability before completely discontinuing mirtazapine.