Is it safe to use fluoxetine (Prozac) and valbenazine (Ingrezza) together?

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Last updated: December 20, 2025View editorial policy

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Using Prozac (Fluoxetine) and Ingrezza (Valbenazine) Together

Yes, it is safe to use fluoxetine (Prozac) and valbenazine (Ingrezza) together—these medications have distinct, non-overlapping mechanisms with no clinically significant pharmacokinetic interactions. 1

Why This Combination Is Safe

Valbenazine and fluoxetine work through completely separate pathways: valbenazine reduces dopamine release via VMAT2 inhibition while fluoxetine increases serotonin availability through selective serotonin reuptake inhibition. 1 Although fluoxetine has moderate effects on CYP2D6 metabolism, valbenazine's metabolic pathway does not create clinically significant interactions with this enzyme system. 1

Key Monitoring Parameters

Watch for Serotonin Syndrome (Low Risk with This Combination Alone)

  • Monitor for serotonin syndrome symptoms if other serotonergic agents are added to the regimen: mental status changes, neuromuscular hyperactivity (myoclonus, hyperreflexia), and autonomic hyperactivity (diaphoresis, diarrhea). 1
  • These symptoms typically arise within 24-48 hours after combining multiple serotonergic medications. 1
  • The risk with fluoxetine and valbenazine alone is minimal since valbenazine is not serotonergic. 1

Standard SSRI Monitoring

  • Continue routine psychiatric monitoring for behavioral activation, particularly during the first month of fluoxetine treatment or with dose increases. 1
  • This is standard practice for any patient on SSRIs and not specific to the combination. 2

Common Pitfalls to Avoid

Do Not Confuse Valbenazine with Antipsychotics

The concern about QT prolongation that applies to antipsychotics does not apply to valbenazine—it is not an antipsychotic and did not demonstrate clinically significant QT prolongation in clinical trials. 1 This is a critical distinction since fluoxetine itself carries FDA warnings about QT prolongation in certain populations (CYP2D6 poor metabolizers, congenital long QT syndrome). 2

Do Not Discontinue Valbenazine Unnecessarily

  • Avoid unnecessary discontinuation of valbenazine, as tardive dyskinesia symptoms will re-emerge if the medication is stopped. 1
  • Plan for long-term treatment if TD improvement is achieved with valbenazine. 1 3

Clinical Context

Valbenazine is the first FDA-approved medication specifically for tardive dyskinesia, with clinically significant efficacy at 80 mg/day (effect size d=0.90). 3 When patients with TD require concurrent antidepressant therapy, fluoxetine can be safely prescribed alongside valbenazine without dose adjustments or special precautions beyond standard monitoring for each individual medication. 1

References

Guideline

Safe Concurrent Use of Ingrezza and Prozac

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Valbenazine for Tardive Dyskinesia.

Clinical schizophrenia & related psychoses, 2017

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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