Mirtazapine Taper Plan for Transition to SNRI
For a patient on 15mg mirtazapine transitioning to an SNRI over 1-2 weeks, reduce the dose by 50% (to 7.5mg) for 3-7 days, then discontinue, while monitoring closely for withdrawal symptoms and adjusting the timeline if needed. 1
Specific Tapering Schedule
Week 1 (Days 1-7):
- Reduce mirtazapine from 15mg to 7.5mg daily (50% reduction) 1
- Continue at 7.5mg for at least 3-7 days to assess tolerance
- Monitor for withdrawal symptoms including anxiety, insomnia, nausea, or mood changes
Week 2 (Days 8-14):
- If withdrawal symptoms are minimal or absent after 3-7 days at 7.5mg, discontinue mirtazapine completely 1
- Begin SNRI at this point according to standard initiation protocols
Why This Approach Works
Mirtazapine has a relatively favorable discontinuation profile compared to other antidepressants due to its 20-40 hour elimination half-life, which provides a natural buffer against abrupt withdrawal 2, 3. At the low dose of 15mg, a single 50% reduction followed by discontinuation is typically well-tolerated over 1-2 weeks 1.
The mechanism of mirtazapine (alpha-2 adrenergic antagonism with enhanced noradrenergic and serotonergic activity) differs substantially from SNRIs, which directly inhibit reuptake of serotonin and norepinephrine 4, 5. This mechanistic difference means there is minimal pharmacological overlap requiring extended cross-tapering.
Adjusting for Withdrawal Symptoms
If withdrawal symptoms become severe or intolerable:
- Return to the previous well-tolerated dose (15mg) temporarily 1
- Extend the time at 7.5mg for an additional 7-14 days before attempting discontinuation 1
- Consider splitting the final taper into smaller steps (e.g., 7.5mg → 3.75mg → discontinuation) if symptoms persist 1
Do not set arbitrary time limits for completing the taper—patient response should guide the timeline 1.
Timing the SNRI Initiation
Optimal approach: Start the SNRI on the same day you discontinue mirtazapine (after the 7.5mg taper period) to minimize the antidepressant-free interval and reduce risk of depressive symptom recurrence.
Alternative approach: If withdrawal symptoms are concerning, you may initiate the SNRI at a low dose while still on 7.5mg mirtazapine for 2-3 days, then discontinue mirtazapine. This brief overlap is generally safe given mirtazapine's unique mechanism 4, 5.
Common Withdrawal Symptoms to Monitor
- Neurological: Dizziness, headache, paresthesias
- Psychiatric: Anxiety, irritability, mood lability, insomnia 5
- Somatic: Nausea, fatigue, flu-like symptoms
- Sleep-related: Insomnia or vivid dreams (particularly relevant given mirtazapine's sedating properties at lower doses) 5, 3
Critical Pitfalls to Avoid
Avoid tapering too quickly, which increases withdrawal symptom risk and potential for depressive relapse 1. The 1-2 week timeline is appropriate for 15mg, but longer tapers may be needed if the patient has been on mirtazapine for years 1.
Time the final discontinuation when the patient has fewer life stressors, as this improves tolerability 1.
Monitor for re-emergence of the symptoms mirtazapine was treating, particularly insomnia and anxiety, which mirtazapine addresses through H1 receptor antagonism and 5-HT2/5-HT3 blockade 4, 3. The SNRI may not immediately address these symptoms as effectively.
Special Considerations for SNRI Transition
When initiating the SNRI (such as venlafaxine or duloxetine), start at standard initial doses and follow standard titration protocols 6. SNRIs require their own gradual titration to minimize gastrointestinal side effects and allow tolerance to develop 7.
Be aware that SNRIs can cause nausea and constipation, which may be particularly noticeable after discontinuing mirtazapine, as mirtazapine's 5-HT3 antagonism provides antiemetic effects 7, 4.