What is the recommended transition schedule from Parnate (tranylcypromine) to Symbyax (olanzapine/fluoxetine)?

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 16, 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.

Recommended Transition Schedule from Parnate (Tranylcypromine) to Symbyax (Olanzapine/Fluoxetine)

When transitioning from Parnate (tranylcypromine), a monoamine oxidase inhibitor (MAOI), to Symbyax (olanzapine/fluoxetine), a minimum washout period of 14 days is required to prevent potentially life-threatening serotonin syndrome.

Understanding the Risks

  • MAOIs like Parnate (tranylcypromine) require special precautions when switching to medications containing serotonergic agents like fluoxetine (a component of Symbyax) due to the risk of serotonin syndrome 1
  • Serotonin syndrome can be fatal and may result from inappropriate co-administration of antidepressants with different mechanisms of action 1
  • The long half-life of fluoxetine (component of Symbyax) requires particular caution during the transition 1

Recommended Transition Protocol

Step 1: Discontinuation of Parnate

  • Gradually taper Parnate over 10-14 days to minimize withdrawal symptoms 2, 1
  • A common tapering schedule involves reducing the dose by approximately 25% every 3-7 days 2
  • Monitor for withdrawal symptoms including anxiety, irritability, insomnia, and mood changes 1

Step 2: Washout Period

  • After complete discontinuation of Parnate, observe a mandatory washout period of at least 14 days 1
  • This washout period is critical to allow complete clearance of the MAOI from the system 1
  • During this period, patients may experience withdrawal symptoms and should be monitored closely 2

Step 3: Initiation of Symbyax

  • Begin Symbyax at a low dose after the 14-day washout period is complete 3
  • Typical starting dose is 6 mg olanzapine/25 mg fluoxetine once daily 3, 4
  • Titrate gradually based on clinical response and tolerability 3

Special Considerations

  • Consider temporary use of benzodiazepines during the washout period to manage anxiety, agitation, or insomnia if clinically indicated 2
  • Patients with bipolar disorder require careful monitoring during the transition to assess for emergence of manic symptoms 2
  • Symbyax has shown efficacy in bipolar depression with a lower risk of treatment-emergent mania compared to antidepressant monotherapy 3, 4

Monitoring During Transition

  • Monitor closely for signs of serotonin syndrome (agitation, hyperthermia, rigidity, autonomic instability) 1
  • Watch for withdrawal symptoms from Parnate (irritability, agitation, insomnia) 1
  • Assess for adverse effects associated with Symbyax including weight gain, metabolic changes, and sedation 3, 4
  • Regular follow-up appointments are essential during the transition period 1

Potential Pitfalls to Avoid

  • Never overlap Parnate and Symbyax administration due to risk of serotonin syndrome 1
  • Do not shorten the recommended 14-day washout period even if the patient experiences worsening of depression 1
  • Avoid abrupt discontinuation of Parnate, as this increases risk of withdrawal symptoms 2, 1
  • Be aware that fluoxetine has a long half-life, which can complicate management if adverse effects occur 1

Remember that this transition requires careful clinical management to ensure patient safety while maintaining effective treatment of the underlying condition.

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.