What is the best approach to tapering mirtazapine (an antidepressant medication) from 15mg to 0mg after being on 30mg, while introducing a Serotonin-Norepinephrine Reuptake Inhibitor (SNRI)?

Tapering Mirtazapine and Introducing an SNRI

Gradually taper mirtazapine from 30mg to 15mg over 1-2 weeks, then from 15mg to 7.5mg for another 1-2 weeks, and finally discontinue after an additional week at 7.5mg, while simultaneously starting the SNRI at its initial therapeutic dose once mirtazapine reaches 7.5mg or lower. 1

Rationale for Gradual Tapering

The FDA label for mirtazapine explicitly states that adverse reactions may occur upon discontinuation or dose reduction, and recommends gradually reducing the dosage rather than stopping abruptly whenever possible 1. This guidance is supported by multiple case reports demonstrating that even after medium-duration treatment (10 weeks) at 30mg daily, abrupt discontinuation can precipitate severe withdrawal symptoms including recurrent panic attacks, anxiety, tremor, nausea, and loss of appetite 2, 3.

Specific Tapering Protocol

Week 1-2: Reduce from 30mg to 15mg

• You have already completed one week at 30mg and one week at 15mg, which represents appropriate initial tapering 1
• Continue at 15mg for at least one additional week to ensure stability 4

Week 3-4: Reduce from 15mg to 7.5mg

• Cut the 15mg dose in half to 7.5mg daily 4
• Monitor closely for withdrawal symptoms including anxiety, nausea, tremor, insomnia, or mood changes 2, 3
• This intermediate step is critical because case reports show withdrawal symptoms can occur even at low doses (15mg) 3

Week 5: Discontinue mirtazapine

• After 1-2 weeks at 7.5mg, discontinue completely 1
• The total taper duration of 4-5 weeks aligns with general antidepressant discontinuation guidance recommending tapers over 10-14 days minimum, though longer tapers (weeks to months) are increasingly recognized as superior 4, 5, 6

Timing of SNRI Introduction

Start the SNRI when mirtazapine reaches 7.5mg or lower, not before. This approach minimizes the risk of serotonin syndrome while providing therapeutic coverage as mirtazapine is withdrawn 6. There is no pharmacological interaction requiring a washout period between mirtazapine and SNRIs (unlike MAOIs, which require 14 days) 1.

Key considerations:

• Begin the SNRI at its standard starting dose per FDA labeling 1
• The overlapping period at low mirtazapine doses (7.5mg) provides a safety buffer against symptom recurrence 6
• Full therapeutic effect of the SNRI will require 4-8 weeks, so some transient symptom return is possible 4

Monitoring During Transition

Schedule follow-up visits every 1-2 weeks during the tapering process to assess for: 4, 7

• Withdrawal symptoms: Anxiety, agitation, nausea, dizziness, tremor, insomnia, flu-like symptoms 2, 6, 3
• Return of depressive symptoms: Monitor for recurrence versus withdrawal (withdrawal symptoms typically emerge within 2-7 days of dose reduction and resolve within 1-2 weeks) 2, 6, 3
• Tolerability of new SNRI: Assess for SNRI-specific side effects and therapeutic response 6

Common Pitfalls to Avoid

Do not abruptly discontinue mirtazapine, even at 15mg, as case reports document severe withdrawal syndromes including panic attacks recurring every 1-2 hours for up to 5 days, requiring medication reinstatement 2, 3. One patient experienced symptoms for 14 days after stopping 15mg daily before requiring reinitiation 3.

Do not mistake withdrawal symptoms for depression relapse. Withdrawal typically presents with somatic symptoms (dizziness, nausea, tremor, flu-like symptoms) alongside psychological symptoms (anxiety, agitation), whereas depression relapse shows gradual onset of core depressive symptoms over weeks 6.

If severe withdrawal symptoms emerge, reinstate the previous mirtazapine dose immediately and slow the taper rate 6. Case reports show symptoms resolve rapidly (within hours to days) upon medication reinstatement 2, 3.

Alternative Approach for High-Risk Patients

For patients with history of severe withdrawal from antidepressants or significant anxiety, consider an even more gradual taper: 5

• 30mg → 22.5mg → 15mg → 11.25mg → 7.5mg → 3.75mg → discontinue
• Each step lasting 1-2 weeks
• This hyperbolic tapering approach (reducing by smaller absolute amounts at lower doses) minimizes receptor-level changes and withdrawal symptoms 5