Auvelity Indication
Auvelity (dextromethorphan hydrobromide/bupropion hydrochloride) is FDA-approved for the treatment of major depressive disorder (MDD) in adults. 1
Mechanism and Rationale
Auvelity combines two active components with distinct mechanisms 1:
- Dextromethorphan: Functions as an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist, modulating glutamate signaling 1, 2
- Bupropion: Serves as a CYP450 2D6 inhibitor that increases dextromethorphan bioavailability by preventing its rapid metabolism, while also contributing noradrenergic and dopaminergic effects 1
Clinical Context
This medication represents a novel treatment option for adults with MDD, offering a rapid onset of action with significant symptom improvement observed as early as 1-2 weeks after initiation 3, 2. In clinical trials, remission rates approached 70% and response rates exceeded 80% in long-term studies 2.
Key Prescribing Considerations
Critical Warnings
Auvelity carries a boxed warning for increased risk of suicidal thoughts and behaviors in pediatric and young adult patients 1, 4. The medication is not approved for use in pediatric patients 1.
Absolute Contraindications 1:
- Seizure disorder
- Current or prior diagnosis of bulimia or anorexia nervosa
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
- Concurrent MAOI use or within 14 days of MAOI discontinuation
- Known hypersensitivity to bupropion, dextromethorphan, or other components
Real-World Usage Patterns
In a large US claims database analysis of 22,288 patients initiating Auvelity within one year of FDA approval 5:
- 28.8% initiated as monotherapy
- 71.2% used as add-on therapy (most commonly with SSRIs or SNRIs)
- 10.1% were treatment-naïve
- 83.7% had previously tried SSRIs, SNRIs, or bupropion monotherapy
This positioning aligns with the broader treatment landscape where second-generation antidepressants remain first-line pharmacotherapy for MDD 6, with Auvelity offering an alternative mechanism for patients requiring additional options.