NMDA receptor antagonist + NDRI combination

Auvelity (dextromethorphan-bupropion) Withdrawal

Auvelity is a newer FDA-approved antidepressant (2022) that combines an NMDA receptor antagonist (dextromethorphan) with an NDRI (bupropion). Discontinuation data is more limited than for older agents. Reported withdrawal patterns appear similar to bupropion alone given the bupropion component dominates the longer-term effects.

By Dr. Ben Soffer, DO — board-certified physician, at-home ketamine therapy in Florida and New Jersey.

Half-life

Dextromethorphan component ~22 hours when combined with bupropion (which inhibits its metabolism); bupropion component ~21 hours.

Withdrawal timeline

Onset— 1-3 days after dose reduction

Mild symptoms can emerge within a few days.

Peak— Week 1

Symptoms typically peak in the first week.

Resolution— 2-3 weeks

Most patients return to baseline within 2-3 weeks.

Common symptoms

  • Fatigue
  • Irritability
  • Mood lability
  • Return of depression symptoms

Less common

  • Headache
  • Sleep changes

Tapering guidance

  • Auvelity is dosed twice daily. A typical taper reduces to once daily for 1-2 weeks, then stops.
  • Coordinate any taper with the prescribing physician.

Where ketamine therapy fits

Auvelity is mechanistically interesting in the ketamine conversation because its dextromethorphan component is an NMDA receptor antagonist, the same receptor family ketamine targets. The two are not redundant (different binding profiles, different downstream effects), but there is clinical overlap. Patients on Auvelity who are considering ketamine should discuss the combination with both prescribing physicians; in practice the two can usually be used together with monitoring.

Check ketamine therapy eligibilityMedication safety with ketamine

Frequently asked questions

How does Auvelity withdrawal compare to SSRI withdrawal?

Auvelity withdrawal appears mild compared to SSRI/SNRI withdrawal, similar to bupropion alone. No prominent brain zaps or severe dizziness. Most discontinuation involves fatigue, mood changes, and return of underlying depression.

Can I take Auvelity and ketamine together?

In most cases yes, with monitoring. Both Auvelity (via its dextromethorphan component) and ketamine work on the NMDA receptor system, but their binding profiles differ. Discuss with both prescribing physicians; combination therapy can usually be done safely.

Important: This page is informational and does not constitute medical advice or a recommendation to start, stop, or change any medication. Tapering psychiatric medications should always be coordinated with the prescribing physician. Compounded ketamine for anxiety, depression, PTSD, and chronic pain is not FDA approved.

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