Spravato vs Auvelity: two newer options, built for different moments.
Spravato and Auvelity both act on glutamate, the brain's main signalling chemical, which sets them apart from older antidepressants. Auvelity is a pill taken twice a day for major depression. Spravato is a nasal spray given in a certified office for depression that hasn't responded to at least two antidepressants. Which fits depends mostly on your history.
Spravato vs Auvelity in one table.
| Spravato (esketamine) | Auvelity (dextromethorphan-bupropion) | |
|---|---|---|
| Approved for | Treatment-resistant depression, on its own or with an oral antidepressant; and, with an oral antidepressant, depression with acute suicidal thoughts | Major depressive disorder in adults |
| How it's taken | Nasal spray you take yourself in a certified office | Tablet at home, twice a day |
| How often | Twice a week in month one, then less often | Every day |
| How it works | Acts on glutamate (NMDA receptor) | Acts on glutamate (NMDA receptor), with bupropion |
| Side effects | Temporary, inside the two hours you rest with us | Ongoing while you take it, such as dizziness, headache, dry mouth or sexual side effects |
| Monitoring | Two hours in our office after every dose | Regular check-ins with your prescriber |
From the SPRAVATO® and AUVELITY® Prescribing Information. No trial has compared the two directly.
Is Spravato or Auvelity more effective?
No study has compared Spravato and Auvelity head to head, and they were tested in different groups of people, so neither can be called more effective. Auvelity was studied in major depression; Spravato in depression that had already failed at least two antidepressants. If you've already tried several pills, including newer ones, that history is what qualifies you for Spravato.
A pill every day, or a visit or two a week.
Auvelity is taken at home every day, and its side effects can come with every dose. Spravato's side effects are temporary: they stay inside the two hours you rest in our office, and most people go home feeling like themselves.
Which works faster, Spravato or Auvelity?
Both are faster than older antidepressants. In Spravato's approval trial, people on Spravato were doing better than the comparison group from day 2 (Popova et al., 2019). In Auvelity's main trial, people improved more than on placebo from the first week (Iosifescu et al., 2022). Because the trials enrolled different people, the timings can't be compared directly.
Who shouldn't take each one?
Auvelity contains bupropion, so its label rules it out for people with a seizure disorder or a current or past eating disorder such as bulimia or anorexia, among others (Auvelity Prescribing Information). Spravato is ruled out by certain blood-vessel conditions, a past bleed in the brain, or an allergy to esketamine or ketamine. Who shouldn't take Spravato.
Can you take Auvelity and Spravato together?
Yes, and in our practice we often do. Both work on the glutamate system, so when the oral antidepressant someone is on isn't doing much, adding Auvelity alongside Spravato is one of the combinations we use most, with excellent results in our patients. There's no formal trial of the two combined, so we look at your full medication list and blood pressure and decide with you and your prescriber.
It isn't a prediction about Spravato.
Even though both act on glutamate, they're different medicines given in different ways. A medicine that didn't work isn't a verdict on you. It's part of what qualifies you for Spravato.
When does Spravato make more sense than Auvelity?
- When you've already tried at least two antidepressants and still aren't well. That's the group Spravato was studied and approved for.
- When you'd rather not add another daily pill, or daily side effects have been the problem before.
- When you want close monitoring while you start: every Spravato dose comes with two hours of our team's attention.
Or both. It doesn't have to be one or the other. Because they work on the same system in different ways, many of our patients take Auvelity as their daily antidepressant alongside Spravato.
Auvelity may make more sense earlier on, before treatment resistance, or for someone who can't get to an office a couple of times a week. That's a conversation for you and your psychiatrist, and we're glad to be part of it.
Eight visits in month one, then fewer.
30 doses
Every day.
Side effectsEvery single day: sedation, dry mouth, sexual side effects, weight gain.
8 visits
Twice a week.
4 visits
Down to once a week.
2–4 visits a month
Down to once a week or every other week. Dashed: weeks you may or may not need.
Side effectsMostly gone by the end of each visit.
Find out if Spravato is an option for you.
Answer a few questions about the treatments you've tried, and we'll tell you whether Spravato is likely to fit.
Name, date of birth and insurer. We check your plan and call you back. No commitment.
Check my coverageRegister once, and our team starts your insurance check and reaches out to schedule your evaluation.
Request an evaluationWhat people ask about Spravato and Auvelity.
What is the difference between Spravato and Auvelity?
Auvelity is a daily pill for major depression. Spravato is a nasal spray given in a certified office for treatment-resistant depression. Both act on glutamate signalling.
Is Auvelity a type of ketamine?
No. Auvelity combines dextromethorphan and bupropion. Spravato is esketamine, which is related to ketamine.
Can Spravato work if Auvelity didn't?
It can. They're different medicines, and a treatment that didn't work is part of the history that qualifies you for Spravato.
Can you take Auvelity and Spravato at the same time?
Yes. We often combine them in our practice, especially when someone's current antidepressant isn't doing much, and we've seen excellent results. We plan it with you and your prescriber.
Which works faster, Auvelity or Spravato?
Both can work faster than older antidepressants: Spravato from day 2 in its approval trial, Auvelity from the first week in its main trial. The trials enrolled different people, so they can't be compared directly.
Does insurance cover Spravato and Auvelity?
Both are covered by many plans, often with prior authorization. We handle the Spravato approval for you.