Auvelity (Dextromethorphan-Bupropion) and Ketamine Therapy | Tovani Health
Auvelity (Dextromethorphan / Bupropion) — NMDA receptor antagonist + CYP2D6-inhibiting boost (FDA-approved for major depressive disorder, 2022)
Verdict at Tovani Health
Real mechanistic overlap with ketamine — both target NMDA; we typically pick one approach rather than combine.
Auvelity alongside ketamine therapy requires individual evaluation. Auvelity is a fixed-dose combination of dextromethorphan (45mg) plus bupropion (105mg), FDA-approved in August 2022 for major depressive disorder. The clinical hook: dextromethorphan is an NMDA receptor antagonist (same primary mechanism as ketamine), and the bupropion is included specifically to inhibit CYP2D6 — slowing DXM metabolism so it builds up to therapeutic NMDA-antagonist plasma levels rather than being rapidly cleared. So Auvelity is functionally trying to be 'oral ketamine in a pill,' which makes the combination with at-home ketamine therapy a real clinical question rather than a routine one. We typically don't run both simultaneously: the mechanistic overlap means we're potentially blocking the same receptor target twice with no clear additive benefit and amplified dissociation/dizziness risk. If you're currently on Auvelity and want to try KAP, we evaluate whether to taper Auvelity first, and the bupropion component's own KAP considerations (mild seizure threshold effect) overlap with our bupropion page guidance. If you're already on KAP, we usually wouldn't add Auvelity. Two NMDA antidepressants is a coordination conversation, not a flat 'no.'
If you take Auvelity regularly and are considering at-home ketamine therapy, eligibility depends on your specific situation — we evaluate case by case. This page covers the brief pharmacologic context and what we do at intake.
How Auvelity interacts with ketamine
Dextromethorphan blocks NMDA receptors (uncompetitive open-channel blocker, like ketamine) and activates sigma-1 receptors. Bupropion's role is dual: contributes its own monoamine reuptake inhibition (NDRI activity) AND inhibits CYP2D6 — the primary enzyme that would otherwise rapidly demethylate DXM to its less-active metabolite dextrorphan. Net: bupropion serves as a pharmacokinetic booster, keeping DXM plasma levels in the therapeutic NMDA-antagonist range across the dosing interval. Bupropion is also itself a CYP2B6 substrate; ketamine is metabolized by CYP3A4 and CYP2B6, so there's a minor CYP2B6 competition story alongside the receptor overlap.
What we do at intake
Disclose current Auvelity dose and how long you've been on it. Tell us what response you've had so we can talk about whether KAP is augmentation, replacement, or a different question. We don't run both simultaneously by default — let's plan the transition.
Bottom line
Auvelity alongside ketamine therapy requires individual evaluation. Auvelity is a fixed-dose combination of dextromethorphan (45mg) plus bupropion (105mg), FDA-approved in August 2022 for major depressive disorder. The clinical hook: dextromethorphan is an NMDA receptor antagonist (same primary mechanism as ketamine), and the bupropion is included specifically to inhibit CYP2D6 — slowing DXM metabolism so it builds up to therapeutic NMDA-antagonist plasma levels rather than being rapidly cleared. So Auvelity is functionally trying to be 'oral ketamine in a pill,' which makes the combination with at-home ketamine therapy a real clinical question rather than a routine one. We typically don't run both simultaneously: the mechanistic overlap means we're potentially blocking the same receptor target twice with no clear additive benefit and amplified dissociation/dizziness risk. If you're currently on Auvelity and want to try KAP, we evaluate whether to taper Auvelity first, and the bupropion component's own KAP considerations (mild seizure threshold effect) overlap with our bupropion page guidance. If you're already on KAP, we usually wouldn't add Auvelity. Two NMDA antidepressants is a coordination conversation, not a flat 'no.'
Ready to find out if at-home ketamine fits your situation?
We’ll note that you’re on Auvelity (Dextromethorphan / Bupropion) at intake. The eligibility check takes 5 minutes and gives you an honest answer about whether at-home ketamine fits your specific situation.
FL and NJ residents only. Benjamin Soffer, DO — Tovani Health.
Sources
The verdict and clinical guidance on this page are based on the following peer-reviewed literature and FDA prescribing information.
- Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthetic and Pain Therapy. Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Clinical Pharmacokinetics. 2016. PMID: 27028535
Clinically reviewed
Reviewed by Benjamin Soffer, DO on May 23, 2026. Dr. Soffer is a board-certified physician (American Board of Internal Medicine) licensed in Florida and New Jersey, prescribing at-home ketamine therapy through Tovani Health.
This page is general information about how this medication interacts with at-home ketamine therapy at Tovani Health. It is not a substitute for medical advice from your prescribing physician about your specific situation. Always discuss medication changes with the doctor who prescribed them.