Patients comparing Spravato with ketamine infusions are usually not choosing between two rival drugs. They are choosing between two regulatory worlds that happen to share a molecule family. One is an approved medicine with a defined indication, a certification system and, in much of Europe, a public funding route. The other is an older generic anaesthetic used off-label, mostly in private clinics, on the strength of an academic evidence base. This page sets the two side by side on the practical points; the clinical detail lives in our full esketamine evidence review and ketamine evidence review, and every clinical fact here is drawn from those two pages.
One molecule family, two products
Racemic ketamine is a 50:50 mix of two mirror-image molecules. Esketamine is one of them, isolated and developed into a distinct nasal-spray medicine that went through the full regulatory trial programme and received an EU-wide marketing authorisation on 18 December 2019. Racemic ketamine has never been through regulatory approval as an antidepressant; it remains a licensed anaesthetic, so depression treatment with it is off-label. Legal, but outside the licence.
Related is not interchangeable. Both act on NMDA glutamate receptors, which is why either can work within hours rather than weeks. But they carry different evidence bases, different supervision rules and different price tags, and a clinic offering one is not offering the other.
Side by side
| Spravato (esketamine) | Ketamine infusions (racemic) | |
|---|---|---|
| Approval | EU marketing authorisation since December 2019 | Licensed as an anaesthetic only; off-label for depression across Europe |
| Licensed indication | Treatment-resistant depression in adults, added to an SSRI or SNRI, after at least two failed antidepressants in the current episode | None for depression; protocols are clinic-defined |
| Route | Nasal spray (28–84 mg), self-administered under direct staff supervision, never dispensed for home use | Intravenous infusion administered by clinic staff |
| Setting | Clinic session with a monitoring period afterwards; no driving for the rest of the day | Clinic session with monitoring and a recovery period |
| Core evidence | Regulatory programme of roughly 1,800 patients: TRANSFORM-2 (short-term benefit), SUSTAIN-1 (relapse prevention), ESCAPE-TRD (win over quetiapine on remission) | Replicated rapid effect since Zarate 2006, confirmed by Cochrane and later meta-analyses; benefit of a single infusion usually fades within one to two weeks |
| Insurance | Publicly reimbursed in much of continental Europe under treatment-resistance criteria | Self-pay almost everywhere; Czechia has partial coverage at one clinic, Norway funds it publicly since 2025 |
| Typical cost to patient | Standard co-payments where reimbursed; expensive self-pay otherwise | Private per-infusion or per-programme fees; see our cost guide |
| Monitoring and risk framework | Blood pressure measured before and after each session; dissociation expected; misuse controls built into the licence; contraindicated after brain bleeds, recent heart attack and in aneurysmal vascular disease | Blood pressure and heart rate rise during infusion; dissociation expected; repeated use calls for monitoring of urinary symptoms (ketamine uropathy) and dependence risk |
| In our directory | 197 Spravato centres across five countries | 32 ketamine clinics across eleven countries |
The geography deserves a second look. The 197 Spravato centres sit in just five countries (Poland, Switzerland, the Netherlands, Germany and Italy) because certification follows national reimbursement programmes, and those programmes concentrate treatment in designated sites. The 32 ketamine clinics are spread across eleven countries because off-label practice follows the private market instead: it appears wherever licensed doctors set up, including England, where the public system reimburses neither.
When each route usually comes up
What follows describes practice as our country and evidence pages record it, not a recommendation of either treatment.
The Spravato route is the one European public systems have built a door for. Where a patient matches the licensed indication, at least two failed antidepressants in the current episode, with treatment added to an ongoing SSRI or SNRI, the national reimbursement machinery can engage: prescription by a psychiatrist, treatment at a certified centre, supervised sessions with observation time. Germany's G-BA, which initially rated the added benefit "not proven" in 2021, upgraded it to "considerable added benefit" in 2023 after the ESCAPE-TRD data, and several payers moved on the strength of that head-to-head result. Czechia added reimbursement in 2025.
Ketamine infusions come up in different circumstances. In England and Wales there is no publicly funded esketamine, so the private ketamine market is the main route that exists at all. Elsewhere, private clinics apply their own criteria after their own screening, which can matter for people who fall outside a national programme's limits. Some clinics pair infusions with structured psychotherapy as ketamine-assisted psychotherapy; our evidence review rates that pairing promising but under-evidenced, since no large trial cleanly separates the drug effect from the psychotherapy. And in Norway the positions are reversed outright: the national system rejected Spravato, then decided in 2025 to fund generic IV ketamine for treatment-resistant depression in the specialist service, off-label and with registry follow-up.
One caution applies to both routes equally. A responsible provider screens cardiovascular health, current medicines and psychiatric history before any first dose, and for repeated ketamine programmes should track urinary symptoms over time. A provider that skips screening is a warning sign, whichever product is on offer.
Frequently asked questions
Is Spravato just patented ketamine?
No. Esketamine is one of the two molecules that make up racemic ketamine, isolated and taken through its own full trial programme to become an approved nasal-spray medicine. Racemic ketamine is the older generic anaesthetic, used off-label for depression by infusion. They share a mechanism; they do not share an evidence base or a regulatory status.
Which has the stronger evidence?
They are strong in different ways. Esketamine's programme is what regulators require: short-term benefit in TRANSFORM-2, relapse prevention in SUSTAIN-1 and a win over an active comparator in ESCAPE-TRD, with moderate rather than dramatic effect sizes. Ketamine's rapid antidepressant effect is the best-established fact in the field, shown since Zarate 2006 and confirmed by the Cochrane review, but the trials are smaller, the benefit of a single infusion usually fades within one to two weeks, and maintenance strategy remains unsettled.
Why is Spravato easier to get covered?
Because reimbursement systems pay for licensed medicines against their approved indication. Esketamine has one; ketamine does not, so its use for depression is off-label and public systems rarely fund it. The exceptions are narrow: partial insurer coverage of ketamine-assisted psychotherapy at one Czech clinic, and Norway's 2025 decision to fund generic IV ketamine in its specialist service.
Can I take either at home?
No. Spravato is self-administered under direct supervision and never dispensed for home use, with blood-pressure checks and an observation period built into the licence, partly because of misuse risk. Ketamine treatment likewise belongs in a monitored clinical setting; repeated dosing carries dependence and bladder-damage risks that need clinical oversight.
How do I find out which route is open where I live?
Coverage is national, so start with your country. Our eligibility check walks through the questions that decide it, the Spravato centre listings and ketamine clinic listings show what operates near you, and the two evidence reviews linked above cover what each treatment can and cannot claim.
Sources
- EMA: Spravato (esketamine) — medicine overview and EPAR
- Popova et al. (2019), American Journal of Psychiatry — TRANSFORM-2
- Daly et al. (2019), JAMA Psychiatry — SUSTAIN-1
- Reif et al. (2023), New England Journal of Medicine — ESCAPE-TRD
- Zarate et al. (2006), Archives of General Psychiatry — single-infusion ketamine in treatment-resistant depression
- Caddy et al. (2015), Cochrane Database of Systematic Reviews — ketamine and other glutamate receptor modulators for depression
- Marcantoni et al. (2020), Journal of Affective Disorders — meta-analysis of IV ketamine for treatment-resistant depression
- McIntyre et al. (2021), American Journal of Psychiatry — ketamine and esketamine evidence synthesis
- Systematic review (2026), Clinical Psychology Review — ketamine-assisted psychotherapies
- British Association of Urological Surgeons (2024), BJU International — consensus on ketamine uropathy
- G-BA: news on the 2023 esketamine benefit reassessment
- Nye metoder / Beslutningsforum (2025) — decision on IV ketamine for treatment-resistant depression
- Blossom (moreblossom.com): Czechia country and reimbursement report
This comparison is for general information only and is not medical advice, a diagnosis, or a recommendation of any treatment. Approved indications, reimbursement rules and clinical evidence change; always verify current information with your national regulator or a licensed clinician who knows your history. If you are in crisis, contact your local emergency number or a crisis line immediately.
This article awaits review by a licensed medical professional.