How do I switch from Duloxetine to Mirtazapine?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: October 15, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Switching from Duloxetine 120mg to Mirtazapine: Recommended Regimen

When switching from duloxetine 120mg daily to mirtazapine, a gradual cross-tapering approach is recommended to minimize withdrawal symptoms and maintain therapeutic efficacy.

Rationale for Switch

  • Mirtazapine is a potent and well-tolerated antidepressant that promotes sleep, appetite, and weight gain, making it particularly useful for patients with insomnia and poor appetite 1
  • Mirtazapine differs from duloxetine by not being a reuptake inhibitor; instead, it enhances noradrenergic neurotransmission through alpha2-autoreceptor blockade 2

Recommended Switching Protocol

Week 1:

  • Reduce duloxetine from 120mg to 90mg daily
  • Start mirtazapine 15mg at bedtime 3
  • Monitor for serotonin syndrome or withdrawal symptoms 4

Week 2:

  • Further reduce duloxetine to 60mg daily
  • Increase mirtazapine to 30mg at bedtime if tolerated and clinically indicated 3

Week 3:

  • Reduce duloxetine to 30mg daily
  • Maintain mirtazapine at 30mg at bedtime (or increase to 45mg if needed and tolerated) 1

Week 4:

  • Discontinue duloxetine completely
  • Continue mirtazapine at optimal dose (30-45mg at bedtime) 3

Important Considerations

Potential Withdrawal Symptoms

  • Abrupt discontinuation of duloxetine can cause withdrawal symptoms including dizziness, nausea, headache, paresthesia, irritability, and nightmares 1
  • Abrupt discontinuation of mirtazapine has been associated with panic attacks and anxiety symptoms 5

Monitoring Parameters

  • Monitor for serotonin syndrome during cross-tapering (symptoms include agitation, hallucinations, rapid heart rate, fever, excessive sweating, shivering, tremor, muscle stiffness, coordination problems) 1
  • Assess sleep quality, as mirtazapine is more sedating than duloxetine 6
  • Monitor for common side effects of mirtazapine including somnolence, increased appetite, weight gain, and dry mouth 1

Dosage Adjustments

  • The recommended starting dose of mirtazapine is 15mg once daily at bedtime 3
  • Dose can be increased to a maximum of 45mg per day based on response 3
  • Allow 1-2 weeks between dose changes to properly evaluate response 3

Special Considerations

  • If insomnia is a prominent symptom, mirtazapine may be particularly beneficial due to its sedating properties 1
  • Mirtazapine is contraindicated with MAOIs; ensure at least 14 days between stopping mirtazapine and starting an MAOI 3
  • Consider drug interactions: strong CYP3A inducers or inhibitors may require dosage adjustments of mirtazapine 3

Advantages of This Approach

  • Cross-tapering minimizes the risk of discontinuation symptoms 4
  • The gradual approach allows time to assess tolerability of mirtazapine while maintaining antidepressant coverage 7
  • Evening dosing of mirtazapine capitalizes on its sedating effects to improve sleep 1

This regimen balances the need to minimize withdrawal symptoms while transitioning to an effective alternative medication with a different mechanism of action.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Mirtazapine: clinical overview.

The Journal of clinical psychiatry, 1999

Research

Switching and stopping antidepressants.

Australian prescriber, 2016

Research

Immediate switching of antidepressant therapy: results from a clinical trial of duloxetine.

Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists, 2005

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.