Ketamine vs Esketamine
Ketamine is an anesthetic used off-label for depression; esketamine (Spravato) is its derivative, approved as a nasal spray under supervision. Compare uses, evidence and risks.
Content last updated . This page has not been medically reviewed.
Safety first. Both medicines can cause sedation, dissociation (feeling detached from your body or surroundings) and breathing problems. The esketamine label requires monitoring for at least two hours after each treatment session because of these risks. [1] Ketamine taken outside medical care, especially with opioids or alcohol, can be life-threatening. [2] For an emergency call 911 (US) or your local emergency number; US Poison Help is 1-800-222-1222; in a US mental health crisis call or text 988. This page is education only and gives no amounts or advice to start, stop or change any medicine. Talk with the prescriber.
Evidence labels used here: approved medicine (name the regulator and indication), promising but limited, mixed, insufficient evidence. Where we looked and found nothing usable, we write "Proper evidence not found."
Definitions
- Ketamine is a chemical compound used as an anesthetic in humans and animals. It is a dissociative, not a classic psychedelic. [2][3] NIDA also notes that illicitly manufactured ketamine exists. [2]
- Esketamine is a derivative of ketamine. The FDA label explains that ketamine is a racemic mixture, meaning it contains two mirror-image forms, arketamine and esketamine. [1] Esketamine is sold in the US as the nasal spray Spravato. [2]
- Both block NMDA receptors, part of the brain's glutamate system. [3][1]
Do not merge the two. They are related but regulated, studied and offered differently.
Side-by-side
| Ketamine | Esketamine (Spravato) | |
|---|---|---|
| FDA-approved use | Anesthetic. NIDA says it is not FDA-approved for any mental health condition. [2] | Treatment-resistant depression in adults; depressive symptoms in adults with major depressive disorder who have acute suicidal ideation or behavior, with an oral antidepressant. [1] |
| Use for depression | Off-label; clinics offer oral, nasal spray, intravenous or intramuscular forms, sometimes with talk therapy. [2] | Intranasal, under direct supervision of a healthcare provider, in a restricted program (REMS). [1] |
| US federal schedule | Schedule III [4] | Schedule III (label lists CIII) [1] |
| Not approved for | Any mental health condition [2] | Pediatric patients; use as an anesthetic [1] |
What research shows
- Esketamine, treatment-resistant depression: approved medicine (US FDA, adults, as above). [1] In the ESCAPE-TRD trial (336 vs 340 people, open-label with blinded raters, industry-funded), remission at week 8 was 27.1% with esketamine nasal spray versus 17.6% with extended-release quetiapine, each added to an antidepressant. [5]
- Ketamine versus esketamine head to head: promising but limited. A 2025 meta-analysis found eight studies (978 people), seven of them observational. Intravenous ketamine and nasal esketamine showed comparable response and remission, with intravenous ketamine possibly acting faster. The authors say large head-to-head randomized trials are needed. [6]
- Several routes are compared in that review, so it does not show that the two molecules themselves differ in effect, only that the evidence is mostly observational. [6]
Risks
- Esketamine label: sedation, dissociation, respiratory depression, potential for abuse and misuse, and increased suicidal thoughts and behaviors in young people taking antidepressants. [1] In trials, 48% to 61% of treated patients developed sedation. [1]
- Ketamine in depression: a systematic review found psychiatric, cardiovascular and neurological side effects reported more often than with placebo, while long-term and repeated-use safety was poorly assessed. [7]
- Nonmedical ketamine: NIDA links heavy long-term use to memory problems, bladder (uropathy) and gut problems, and problems reported to poison centers rose 81% from 2019 to 2021. [2]
- Pregnancy: the esketamine label says it may cause fetal harm based on animal findings with racemic ketamine. [1]
Legal and regulatory note
Laws change and this is not legal advice. For the United States, ketamine appears in the federal Schedule III list in 21 CFR 1308.13, read 2026-10-22. [4] Other countries: not verified.No universal winner
Which medicine, if any, suits a person is a decision for their prescriber. Related guides: ketamine, esketamine (Spravato) and treatment-resistant depression evidence.Frequently asked questions
Is esketamine the same as ketamine?
No. Esketamine is one of the two mirror-image forms in racemic ketamine and is a separately approved medicine. [1]
Which one is FDA-approved for depression?
Esketamine nasal spray is approved for treatment-resistant depression in adults. Ketamine is approved as an anesthetic, not for depression. [1][2]
Is ketamine safer than esketamine?
No source we read supports a safety ranking. The available head-to-head evidence is mostly observational. [6]
Is a ketamine clinic offering the same thing as Spravato?
Not necessarily. NIDA notes clinics offer ketamine off-label in several forms, while the esketamine label applies only to Spravato. Ask a licensed clinician about risks for your own health. [2][1]
References
- US Food and Drug Administration, SPRAVATO (esketamine) nasal spray, CIII: prescribing information, label revised 01/2025. Read 2026-10-22.
- NIDA, Ketamine, National Institute on Drug Abuse. Read 2026-10-22.
- NIDA, Psychedelic and Dissociative Drugs, National Institute on Drug Abuse. Read 2026-10-22.
- US Code of Federal Regulations, 21 CFR 1308.13, Schedule III, read through the eCFR API. Read 2026-10-22.
- Reif A et al. Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression. N Engl J Med. 2023. PubMed 37792613. Read 2026-10-22.
- Elmosalamy A et al. Intravenous ketamine versus esketamine for depression: a systematic review and meta-analysis. Ther Adv Psychopharmacol. 2025. PubMed 41244961. Read 2026-10-22.
- Short B et al. Side-effects associated with ketamine use in depression: a systematic review. Lancet Psychiatry. 2018. PubMed 28757132. Read 2026-10-22.