dextromethorphan bupropion

Adjunctive therapy

Brands: Auvelity

Last reviewed 2026-01-05

Reviewed by PsychMed Editorial Team.

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Quick answers

What is dextromethorphan bupropion?
Dextromethorphan-bupropion (brand Auvelity) is an oral combination antidepressant indicated for major depressive disorder (MDD) in adults (label).
What is Auvelity?
Auvelity is a brand name for dextromethorphan bupropion.
What is Auvelity (dextromethorphan bupropion) used for?
Label indications include: Major depressive disorder in adults (label).
What drug class is Auvelity (dextromethorphan bupropion)?
Combination antidepressant pairing dextromethorphan (NMDA receptor antagonist and sigma-1 receptor agonist) with bupropion, which inhibits CYP2D6 to increase dextromethorphan exposure; used for major depressive disorder.
What strengths does Auvelity (dextromethorphan bupropion) come in?
Extended-release tablets: 45 mg dextromethorphan / 105 mg bupropion (fixed-dose) (label).
What is dextromethorphan bupropion hydrochloride (HCl)?
Extended-release tablets contain 45 mg dextromethorphan hydrobromide and 105 mg bupropion hydrochloride (label).

Snapshot

Class: Adjunctive therapy
Common US brands: Auvelity
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2026-01-05

Label indications

Major depressive disorder in adults (label).

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Clinical Highlights

Dextromethorphan-bupropion (brand Auvelity) is an oral combination antidepressant indicated for major depressive disorder (MDD) in adults (label). It pairs dextromethorphan (an NMDA receptor antagonist and sigma-1 receptor agonist) with bupropion, which inhibits CYP2D6 to increase dextromethorphan exposure; this interaction is a core part of the product’s pharmacology (label).

Because it includes bupropion, key risk considerations include seizure risk (dose-related), hypertension, and activation/insomnia in susceptible patients; these risks often drive screening and early follow-up (label/clinical).
As with other antidepressants, monitoring for suicidal thoughts and behaviors is emphasized during initiation and dose changes, especially in younger adults (label).
The compare view, dextromethorphan-bupropion evidence feed, and dextromethorphan-bupropion print page help contextualize adverse-effect and interaction trade-offs across antidepressant options.

Dosing & Formulations

Extended-release tablets contain 45 mg dextromethorphan hydrobromide and 105 mg bupropion hydrochloride (label). The recommended starting regimen is one tablet once daily in the morning; after 3 days, increase to one tablet twice daily given at least 8 hours apart (label).

The label states not to exceed two doses within the same day; missed doses are generally not “made up” with extra dosing because seizure risk is dose-related (label/clinical).
Dose adjustments are required for certain situations: moderate renal impairment, known CYP2D6 poor metabolizers, or concomitant strong CYP2D6 inhibitors (once-daily dosing) (label).
Because the combination is fixed-dose, dose strategy often focuses on tolerability and interaction management rather than fine-grained dose titration of each component (clinical).

Monitoring & Risks

Seizure risk is a central safety issue (bupropion component). Clinicians commonly screen for seizure disorder, eating disorder history, heavy alcohol use, and recent sedative/hypnotic withdrawal (label/clinical). Blood pressure increases can occur; monitoring is especially relevant when other noradrenergic agents or stimulants are also used (label/clinical).

Dizziness, nausea, headache, and somnolence are common early adverse effects in trials; early follow-up is often used to assess function and driving safety (label/clinical).
Serotonin syndrome is a rare but clinically important risk when combined with serotonergic agents; prompt evaluation is typical if symptoms emerge (label/clinical).
In bipolar-spectrum illness, antidepressants can precipitate mania/hypomania; clinicians often document screening and monitoring plans when history suggests risk (clinical).

Drug Interactions

MAOIs are contraindicated (and require washout) due to risk of serious interactions including hypertensive crisis and serotonin syndrome (label). Strong CYP2D6 inhibitors raise dextromethorphan concentrations; the label recommends once-daily dosing in this setting and monitoring for adverse effects such as somnolence and dizziness (label).

Strong CYP2B6 inducers (e.g., carbamazepine) can reduce exposure to both components and are generally avoided (label).
Bupropion and its metabolites inhibit CYP2D6 and can increase exposure to CYP2D6 substrates (including some antidepressants, antipsychotics, and beta-blockers); interaction review is often a deciding factor in polypharmacy regimens (label/clinical).

Practice Notes

In real-world use, success often depends on matching the medication to symptom profile (depression with prominent fatigue vs insomnia/anxiety) and proactively managing activation and sleep effects (clinical). When symptom improvement is limited after an adequate trial, clinicians typically reassess diagnosis, adherence, comorbidities, and psychotherapy engagement rather than continuing indefinitely without a defined goal (APA/clinical).

Because the regimen is scheduled (not PRN), adherence routines and early tolerability check-ins are commonly emphasized (clinical).

References

Auvelity (dextromethorphan AND Bupropion) Extended Release Tablets Prescribing Information — DailyMed (2026)
Efficacy AND Safety OF AXS 05 (dextromethorphan Bupropion) IN Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (gemini) — Journal of Clinical Psychiatry (2022)
APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)