Short answer: Esketamine (Spravato) is a nasal spray for treatment-resistant depression and for depression with suicidal thoughts. It is a form of ketamine, given only in certified clinics where patients are monitored for at least two hours. It is a Schedule III controlled substance and is never dispensed to take home.
Key takeaways
- What it is: Esketamine is a nmda receptor antagonist (nasal) and a Schedule III controlled substance in the US.
- Main uses: Treatment-resistant depression.
- Timing: effects start in minutes (dissociation); hours to days (mood) and last dissociation about 1 to 2 hours.
- Most dangerous mix: Benzodiazepines, opioids, alcohol, which can cause more sedation.
- Naloxone: it does not reverse this drug, but give it whenever opioids could be involved.
- Dependence risk: Moderate.
- Legal route: only with a prescription from a DEA-registered clinician, filled by a licensed pharmacy.
What is esketamine?
Esketamine is approved for adults with treatment-resistant depression, either with an oral antidepressant or, since January 2025, on its own, and with an oral antidepressant for major depression with acute suicidal thoughts or behavior.
It is the S-form of ketamine. It works on the glutamate system rather than serotonin, which may explain why it can help people for whom standard antidepressants failed.
Quick facts
| Fact | Esketamine |
|---|---|
| Generic name | Esketamine hydrochloride |
| Brand names | Spravato |
| Drug class | NMDA receptor antagonist |
| US legal status | Schedule III; restricted distribution (REMS) |
| Approved uses | Treatment-resistant depression (with an oral antidepressant or alone); major depression with suicidal thoughts or actions |
| Forms | Nasal spray device, 28 mg each |
| Onset | Within hours to days |
| Monitoring | At least 2 hours after each dose |
| Half-life | 7 to 12 hours |
How long does esketamine last?
- Starts working: Minutes (dissociation); hours to days (mood)
- Effects last: Dissociation about 1 to 2 hours
- Half-life: 7 to 12 hours
Timing varies with the dose, the form, how it is taken, liver and kidney function, age, and other drugs taken at the same time.
What are the biggest risks of esketamine?
The FDA requires boxed warnings, its strongest, on esketamine products, including:
- Sedation, dissociation, and breathing depression; patients must be monitored for at least 2 hours after each dose.
- Potential for abuse and misuse.
- Increased risk of suicidal thoughts and behaviors in children, teens, and young adults taking antidepressants.
Common side effects include dissociation, dizziness, nausea, sedation, spinning sensation, numbness, anxiety, raised blood pressure, vomiting, and feeling drunk.
Who should not use it: people with aneurysms or arteriovenous malformations, or a history of bleeding in the brain, because it raises blood pressure.
What should you never mix with esketamine?
| Combined with | What happens | Label guidance |
|---|---|---|
| Benzodiazepines, opioids, alcohol | More sedation | Monitor closely |
| Stimulants, MAOIs | Raised blood pressure | Monitor blood pressure |
| Nasal steroids or decongestants | May change absorption | Use at least 1 hour before Spravato |
Check any combination with the DoseUses combination checker or ask a pharmacist.
What are the signs of an esketamine overdose, and what should you do?
Because it is only given under supervision in measured doses, overdose is rare. Excess effects would include heavy sedation, dissociation, and high blood pressure.
If someone may have overdosed
- Call 911 if the person is unresponsive, breathing slowly, having a seizure, very hot, or violently agitated.
- Place an unresponsive person on their side so they do not choke if they vomit.
- Keep them away from roads, water, and heights. People on dissociatives often cannot feel pain or judge danger.
- If opioids could be involved, give naloxone. It will not harm the person.
What happens when esketamine treatment stops?
No withdrawal syndrome was seen in trials. Stopping maintenance treatment raises the risk of depression returning; trials showed relapse was more likely in patients who stopped than in those who continued.
- WeeksWatch moodDepression can return gradually.
- MonthsRelapse riskHigher after stopping maintenance.
- OngoingPlan with the prescriberDecide together on frequency and duration.
See the withdrawal timelines and the full esketamine withdrawal guide.
Is esketamine legal?
In the United States, esketamine is a Schedule III controlled substance. The only legal way to get it is with a prescription from a clinician registered with the Drug Enforcement Administration (DEA), filled by a licensed pharmacy. Depending on state law, that can be a physician, nurse practitioner, or physician assistant.
- Refills: a Schedule III prescription can be refilled up to five times within six months of the date it was written. After that, a new prescription is needed.
- Telehealth: federal flexibilities let DEA-registered clinicians prescribe Schedule II to V medicines after a telemedicine visit, without a prior in-person exam, through December 31, 2026. A permanent DEA rule was under final review in late 2026. State rules can be stricter.
- Monitoring: prescribers and pharmacists in most states check a prescription drug monitoring program, a database of controlled-substance prescriptions, before prescribing or dispensing.
Outside the United States
| Country | Status |
|---|---|
| European Union | Approved prescription medicine (Spravato) |
| United Kingdom | Licensed but not recommended by NICE; Class B |
| Canada | Approved prescription medicine |
| International | Not under UN control |
Frequently asked questions about esketamine
How fast does Spravato work?
Some people notice improvement within hours to days, faster than typical antidepressants, which take weeks.
Can I drive after Spravato?
No. You must not drive until the next day after a restful sleep.
Is Spravato the same as ketamine?
It is the S-form of ketamine, given as a nasal spray. Ketamine infusions for depression are off-label; Spravato is FDA-approved.
Can Spravato be used alone?
Yes. Since January 2025, it is approved without an oral antidepressant for treatment-resistant depression.
Sources
- Spravato (esketamine) prescribing information, DailyMed, US National Library of Medicine.
- Controlled Substance Schedules, DEA Diversion Control Division.
- 21 CFR 1306.22, Refilling of prescriptions (Schedules III and IV), Electronic Code of Federal Regulations.
- Prescribing controlled substances via telehealth, US Department of Health and Human Services.
- BeSafeRx: Your Source for Online Pharmacy Information, US Food and Drug Administration.
- Safe Pharmacy, National Association of Boards of Pharmacy.
- International drug control conventions, United Nations Office on Drugs and Crime.
This guide summarizes the sourced DoseUses Esketamine profile, written from FDA labels, DEA rules, and federal health agencies. It is educational and is not medical advice. Last updated October 5, 2026.
