Auvelity
Generic: dextromethorphan / bupropion · Brand: Auvelity® · Class: NMDA Receptor Antagonist + NDRI
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How It Works
Auvelity is a first-in-class oral antidepressant combining two medications: dextromethorphan (DXM) and bupropion. DXM is an NMDA receptor antagonist — it blocks glutamate receptors in the brain, which is the same mechanism as ketamine. Bupropion serves a dual purpose: it acts as an antidepressant itself (NDRI) while also slowing the breakdown of DXM in the body, allowing it to reach therapeutic levels. Together, this combination works on glutamate, serotonin, norepinephrine, and dopamine simultaneously — making it uniquely effective and fast-acting compared to traditional antidepressants. Many patients notice improvement within 1–2 weeks, significantly faster than SSRIs or SNRIs.
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What It Treats
Major Depressive Disorder (MDD)FDA-approved for adults — the first new oral antidepressant mechanism approved in decades
Treatment-Resistant DepressionOften considered when SSRIs and SNRIs have not provided adequate relief
Depression with Slow Response HistoryFaster onset makes it a strong option when previous antidepressants took too long to work
Pseudobulbar Affect (PBA)DXM/quinidine (Nuedexta) is related — Auvelity may also help with emotional lability
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Dosing Overview
| Phase | Dose | Timing | Notes |
|---|---|---|---|
| Days 1–3 Starting dose | 45/105 mg | Once daily (AM) | Take with food |
| Day 4+ Target dose | 45/105 mg | Twice daily | Morning and evening |
| Maximum Do not exceed | 45/105 mg BID | Twice daily | No higher doses approved |
Each tablet contains dextromethorphan 45 mg + bupropion 105 mg. Must be swallowed whole with food. Space doses at least 8 hours apart.
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What to Expect — Timeline
1
Week 1
Some patients notice early mood improvement — faster than any traditional antidepressant
2
Week 2
Many patients report meaningful improvement by end of week 2 in clinical trials
4–6
Weeks 4–6
Full antidepressant effect typically established — reassess response with provider
3m+
3+ Months
Continued treatment for sustained remission; duration discussed with your provider
⚡ Faster than most antidepressants. In clinical trials, Auvelity showed significant antidepressant effects as early as week 1–2 — much faster than the 4–8 weeks typical of SSRIs and SNRIs. This does not mean it works instantly, but the onset is notably quicker.
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Side Effects
Common (often temporary)
- Dizziness
- Headache
- Diarrhea
- Drowsiness
- Dry mouth
- Sexual side effects
- Hyperhidrosis (sweating)
- Nausea
Call us if you notice
- Dissociation or feeling detached
- Hallucinations or confusion
- Worsening depression or suicidal thoughts
- Seizures
- Significant increase in blood pressure
- Serotonin syndrome signs
- Hypomania or mania
Dizziness and drowsiness are most common early on and often improve. Because DXM affects glutamate receptors similarly to ketamine, some dissociative effects are possible — contact your provider if you feel detached from reality or have unusual perceptual experiences.
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Tips for Success
Always With FoodMust be taken with food — improves absorption and reduces side effects.
Space 8 Hours ApartWhen taking twice daily, space doses at least 8 hours apart.
Swallow WholeDo not crush, chew, or split tablets — they must be taken intact.
Use Caution DrivingDizziness and drowsiness can occur — be careful with driving until you know how it affects you.
Avoid AlcoholAlcohol significantly increases dizziness and dissociative effects with Auvelity.
Track Your MoodNote changes week by week — the faster onset means you may see early signals sooner.
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Important Safety Information
Black Box Warning (under 25): Antidepressants may increase risk of suicidal thinking in children, adolescents, and young adults, especially in the first few weeks. Monitor closely and contact us right away if new or worsening thoughts of self-harm appear.
MAOIs — Absolutely Contraindicated: Do not take Auvelity within 14 days of stopping an MAOI. Do not start an MAOI within 14 days of stopping Auvelity. This combination can be life-threatening.
Seizure Risk: Contains bupropion, which lowers the seizure threshold. Do not use if you have a seizure disorder, bulimia, or anorexia nervosa. Never exceed the prescribed dose.
Dissociation / Psychosis Risk: DXM can cause dissociative symptoms or, rarely, psychosis — especially at higher doses or when combined with other substances. Avoid alcohol and recreational drug use while taking Auvelity.
Many Drug Interactions: Auvelity interacts with MAOIs, opioids (especially tramadol), other DXM-containing products (cough medicines), serotonergic medications, and CYP2D6 inhibitors. Always share your full medication list — including over-the-counter medications.
Blood Pressure: Contains bupropion which can raise blood pressure. Monitor blood pressure periodically, especially early in treatment.
Pregnancy & Breastfeeding: Limited safety data available. Discuss risks and benefits with your provider. Do not stop without consultation.
Questions? I am here.
Reach me between appointments if you have concerns about side effects, notice mood changes, or have questions about your medication. You do not have to wait until your next visit.
360-389-3712
info@rootedmindspsychiatry.com