Is hydroxyzine safe to use with Parnate (tranylcypromine), a monoamine oxidase inhibitor (MAOI)?

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Hydroxyzine and Parnate (Tranylcypromine) Combination

Hydroxyzine can be safely used with Parnate (tranylcypromine), as hydroxyzine is an antihistamine without serotonergic or sympathomimetic properties that would interact with MAOIs.

Mechanism and Safety Profile

Hydroxyzine is an H1-receptor antagonist (antihistamine) used primarily for anxiety and allergic conditions 1. Unlike medications that are contraindicated with MAOIs, hydroxyzine does not:

  • Increase serotonin levels (it is not a serotonin reuptake inhibitor)
  • Have sympathomimetic activity (it does not increase norepinephrine or dopamine)
  • Inhibit monoamine oxidase enzymes

Medications That ARE Contraindicated with Parnate

The following drug classes pose serious risks when combined with MAOIs like Parnate and should be avoided 2:

  • Sympathomimetic agents (phentermine, pseudoephedrine, phenylephrine) - risk of hypertensive crisis 2
  • Serotonergic antidepressants (SSRIs, SNRIs, tricyclics) - risk of serotonin syndrome 2, 3, 4
  • Certain opioids (meperidine, tramadol, methadone, dextromethorphan) - risk of serotonin toxicity 3, 5
  • Other MAOIs - risk of hypertensive crisis and reduced efficacy 2

Key Distinction

Hydroxyzine does not fall into any of these contraindicated categories. The primary side effects of hydroxyzine are sedation and drowsiness 1, which do not interact with MAOI mechanisms. The antihistamine properties of hydroxyzine work through a completely different pathway than monoamine oxidase inhibition.

Clinical Considerations

  • Monitor for additive sedation when combining hydroxyzine with Parnate, as both medications can cause drowsiness 1
  • Hydroxyzine has been studied and used safely for generalized anxiety disorder without concerns regarding MAOI interactions 1
  • The combination may actually be beneficial for patients on MAOIs who need additional anxiolytic therapy without the risks associated with serotonergic agents 6

References

Research

Hydroxyzine for generalised anxiety disorder.

The Cochrane database of systematic reviews, 2010

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Safety of Using Strattera (Atomoxetine) and Remeron (Mirtazapine) Together

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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.

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