What are the indications for Auvelity (dextromethorphan-bupropion)?

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Auvelity Indications

Auvelity (dextromethorphan-bupropion) is FDA-approved exclusively for the treatment of major depressive disorder (MDD) in adults. 1, 2

Primary Indication

  • Major Depressive Disorder (MDD): Auvelity is indicated as a treatment option for adults with MDD, representing a mechanistically novel approach that targets glutamatergic signaling through NMDA receptor antagonism and sigma-1 receptor agonism (dextromethorphan component) combined with dopamine-norepinephrine reuptake inhibition (bupropion component). 1, 2

Clinical Context for Use

Auvelity can be deployed across multiple treatment scenarios in MDD:

  • First-line therapy: Can be initiated as initial pharmacotherapy for MDD. 2
  • Second-line option: Appropriate when patients have failed to achieve remission with serotonin-targeting agents (SSRIs/SNRIs). 2
  • Treatment-resistant depression: Suitable for patients who have not responded adequately to prior antidepressant trials. 2
  • Add-on therapy: Real-world data shows 71.2% of patients initiated Auvelity as add-on treatment, most commonly combined with SSRIs (10.7%) or SNRIs (6.5%). 3
  • Monotherapy: 28.8% of patients in real-world practice initiated Auvelity as monotherapy. 3

Key Clinical Advantages

  • Rapid onset of action: Significant reductions in Montgomery-Åsberg Depression Rating Scale (MADRS) scores observed within 2 weeks, distinguishing it from traditional monoamine-based antidepressants that typically require 4-8 weeks. 1, 4
  • High remission rates: Long-term studies demonstrate remission rates approaching 70% and response rates exceeding 80% with sustained treatment. 1

Important Limitations

  • Not approved for other indications: Despite containing bupropion, Auvelity is NOT indicated for smoking cessation, seasonal affective disorder, obesity management, or any other condition for which bupropion monotherapy might be used. 1, 2
  • Adult population only: No pediatric indication exists, and the boxed warning specifically highlights increased risk of suicidal thoughts and behaviors in pediatric and young adult patients. 5
  • Preliminary evidence only for bipolar depression: While DXM efficacy has been preliminarily reported in bipolar depression, this is not an FDA-approved indication and requires further study. 4

Contraindications to Consider

When evaluating Auvelity for MDD, absolute contraindications include:

  • Seizure disorder or history of seizures (bupropion lowers seizure threshold with 0.1% risk at therapeutic doses). 6, 7, 8
  • Current or prior diagnosis of bulimia or anorexia nervosa (increased seizure risk). 7, 8
  • Concurrent MAOI use or within 14 days of MAOI discontinuation. 7, 8
  • Uncontrolled hypertension. 7
  • Angle-closure glaucoma. 7, 8

References

Research

Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder.

Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology, 2023

Research

New Combination Drug for Depression.

The American journal of nursing, 2023

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Bupropion Contraindications and Precautions

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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