Tapering Remeron (Mirtazapine) from 15mg
Gradually reduce mirtazapine by 10% of the current dose every 2-4 weeks, tapering down to very small doses (as low as 1-2mg) before complete discontinuation to minimize withdrawal symptoms. 1, 2
Recommended Tapering Schedule
The FDA label explicitly states to "gradually reduce the dosage of mirtazapine tablets rather than stopping abruptly whenever possible" to prevent adverse reactions upon discontinuation. 1 Based on modern tapering principles for antidepressants, the following approach is recommended:
Week-by-Week Protocol
- Weeks 1-2: Reduce from 15mg to 13.5mg (10% reduction) 2, 3
- Weeks 3-4: Reduce to 12mg (10% of 13.5mg) 2
- Weeks 5-6: Reduce to 10.8mg (10% of 12mg) 2
- Continue this pattern: Each reduction should be 10% of the current dose, not the original 15mg dose 2, 3
Key Tapering Principles
- Use hyperbolic (percentage-based) reductions, not linear reductions, as research demonstrates this maintains more consistent receptor occupancy and minimizes withdrawal symptoms 2, 4
- Never use alternate-day dosing (e.g., 15mg every other day) as this creates severe fluctuations in receptor occupancy and significantly increases withdrawal risk 3
- Taper to very small final doses (1-2mg) before complete cessation, as stopping from even "low" therapeutic doses causes abrupt changes in receptor activity 2, 4
Obtaining Small Doses
Since mirtazapine tablets come in 7.5mg, 15mg, 30mg, and 45mg strengths, you will need strategies to achieve the small incremental reductions:
- Request liquid formulation if available for precise dosing 2
- Use a compounding pharmacy to create custom lower-dose capsules 2
- Tablet splitting may work initially but becomes impractical at lower doses 2
Timeline Expectations
- Minimum duration: 3-4 months for a complete taper from 15mg 5, 2
- More conservative approach: 6-12 months may be better tolerated, especially if the patient has been on mirtazapine for years 2
- The taper rate must be determined by patient tolerance, not arbitrary timelines—pauses are acceptable when withdrawal symptoms emerge 5
Monitoring and Managing Withdrawal Symptoms
Common Withdrawal Symptoms to Monitor
- Physical: Insomnia, anxiety, nausea, headache, dizziness, sweating, tremor 1, 2
- Neuropsychiatric: Irritability, mood changes, "brain zaps," flu-like symptoms 2
Management Strategies
- If withdrawal symptoms occur: Return to the previous well-tolerated dose and slow the taper further (reduce by 5% instead of 10%) 2, 3
- For insomnia during taper: Consider short-term trazodone 25-50mg at bedtime 6
- For anxiety symptoms: Cognitive behavioral therapy significantly increases taper success rates 6
- For muscle aches: Acetaminophen or NSAIDs 5, 6
Critical Pitfalls to Avoid
- Never taper faster than 10% every 2 weeks—older guidelines recommending 2-4 week tapers to minimum therapeutic doses show minimal benefit over abrupt discontinuation 2
- Never stop at 7.5mg thinking it's "low enough"—this still represents significant receptor occupancy and abrupt cessation will cause withdrawal 2, 4
- Never abandon the patient during tapering—maintain close follow-up even if the taper is unsuccessful 5, 6
- Never use alternate-day dosing as a tapering strategy 3
Special Considerations
- Mirtazapine's mechanism: As a noradrenergic and specific serotonergic antidepressant (NaSSA), it blocks α2-adrenergic receptors and 5-HT2/5-HT3 receptors, with an elimination half-life of approximately 22 hours 7, 8
- Drug interactions during taper: If the patient is on CYP3A4 inhibitors (ketoconazole, clarithromycin) or inducers (carbamazepine, phenytoin), dosage adjustments may be needed 1
- Older guideline context: The 2002 guideline suggesting "discontinuing an antidepressant over 10 to 14 days limits withdrawal symptoms" is outdated and contradicted by modern evidence showing much slower tapers are necessary 5, 2