How do I taper mirtazapine before starting an SNRI?

Mirtazapine Tapering Before Starting an SNRI

Mirtazapine should be gradually tapered rather than stopped abruptly, with dose reductions of approximately 25% every 1-2 weeks, though no formal tapering is strictly required before initiating an SNRI since mirtazapine lacks significant serotonergic reuptake inhibition. 1

Key Principle: Why Tapering Matters

• The FDA label explicitly states that mirtazapine should be gradually reduced rather than stopped abruptly whenever possible to minimize discontinuation adverse reactions 1
• Abrupt discontinuation of mirtazapine after even medium-duration therapy (10 weeks) has been associated with severe withdrawal symptoms including recurrent panic attacks, palpitations, dyspnea, retrosternal pain, dizziness, nausea, and fear of dying 2
• These withdrawal symptoms can persist for days to weeks until mirtazapine is reintroduced 2

Recommended Tapering Protocol

Reduce mirtazapine by 25% of the current dose every 1-2 weeks until discontinuation 1

Specific Tapering Schedule Example:

• Week 1-2: If on 30mg daily, reduce to 22.5mg (or practically 22mg using 15mg + 7.5mg split tablet)
• Week 3-4: Reduce to 15mg daily
• Week 5-6: Reduce to 7.5mg daily (half of 15mg tablet)
• Week 7: Discontinue completely

Dose changes should not be made more frequently than 1-2 week intervals to allow sufficient time for evaluation of response to each dose reduction 1

Timing of SNRI Initiation

You can begin the SNRI immediately after completing the mirtazapine taper without requiring a washout period 3

• Unlike MAOIs which require a 14-day washout period, mirtazapine does not inhibit serotonin reuptake and therefore poses minimal risk of serotonin syndrome when transitioning to an SNRI 3, 4
• Mirtazapine lacks comparable evidence of analgesic efficacy compared to SNRIs and works through different mechanisms (alpha-2 adrenergic blockade rather than serotonin-norepinephrine reuptake inhibition) 3

Alternative Approach: Cross-Titration

If withdrawal symptoms are a concern, you may initiate the SNRI at low doses while simultaneously beginning the mirtazapine taper 5

• Start the SNRI at the lowest available dose (e.g., duloxetine 30mg once daily) 3
• Begin reducing mirtazapine by 25% every 1-2 weeks concurrently 1
• This cross-titration strategy provides continuous antidepressant coverage and may minimize withdrawal symptoms 5

Monitoring During Tapering

Monitor for withdrawal symptoms at each dose reduction before proceeding to the next step:

• Drowsiness or paradoxical insomnia 4, 6
• Increased anxiety or panic attacks 2
• Nausea, dizziness, or cardiovascular symptoms (palpitations, chest pain) 2
• Changes in appetite or weight 4, 6

If severe withdrawal symptoms develop, return to the previous well-tolerated dose and slow the taper further 5

Critical Pitfalls to Avoid

• Never discontinue mirtazapine abruptly, even after short-term use, as this significantly increases the risk of severe withdrawal symptoms including panic attacks 1, 2
• Do not rush the taper—the goal is tolerability and durability, not speed 7, 8
• Do not assume mirtazapine requires the same precautions as SSRIs or MAOIs when switching to an SNRI—it has a fundamentally different mechanism of action 3, 4

Special Considerations

In patients with hepatic or renal insufficiency, use even more gradual dose reductions and closer monitoring 6, 9

• Liver impairment causes approximately 30% decrease in mirtazapine clearance 9
• Severe renal impairment causes 50% decrease in clearance 9
• The elimination half-life ranges from 20-40 hours, supporting once-daily dosing during tapering 6, 9

Why This Approach is Different from Other Antidepressants

Mirtazapine's unique pharmacology means it does not require the same washout periods as serotonergic antidepressants:

• It enhances noradrenergic and serotonergic neurotransmission via alpha-2 adrenergic receptor blockade, not reuptake inhibition 4, 6
• It directly blocks 5-HT2 and 5-HT3 receptors while the increased serotonin release stimulates 5-HT1 receptors 6
• This mechanism creates minimal risk of serotonergic interactions when transitioning to SNRIs 3, 4