The practical difference is that esketamine nasal spray (Spravato) has specific FDA-approved uses for adults with depression and must be given under a restricted safety program; ketamine injection is FDA-labeled as an anesthetic, and IV ketamine used for depression is off-label. They are related medicines, but not interchangeable products or care pathways. Whether either is appropriate depends on a clinician’s assessment—not on the chemical distinction alone.
What’s the difference between ketamine and esketamine?
Ketamine contains two mirror-image forms, called enantiomers. Esketamine is the S-enantiomer of ketamine; racemic ketamine contains both S- and R-enantiomers. The Drug Enforcement Administration describes the S-enantiomer as the more potent one, but that chemical fact does not show that esketamine is clinically more effective for depression.
Spravato is the brand name for intranasal esketamine. “Ketamine” in the depression-treatment context often refers to ketamine hydrochloride given intravenously at a subanesthetic dose. The route and regulatory status matter: the nasal spray has a labeled depression indication and mandated safeguards, while IV ketamine for depression is off-label.
Is Spravato the same as ketamine?
No. Spravato contains esketamine, a component form of ketamine, but it is a distinct prescription product with its own FDA labeling and access requirements. It is not simply another name for ketamine, and a patient should not substitute one for the other.
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Is esketamine FDA approved for depression?
Yes. The 2025 FDA prescribing information lists two adult indications for Spravato:
- Treatment-resistant depression (TRD): treatment as monotherapy or in conjunction with an oral antidepressant.
- Depressive symptoms in major depressive disorder with acute suicidal ideation or behavior: treatment in conjunction with an oral antidepressant.
The second indication concerns depressive symptoms in a defined clinical setting. It should not be interpreted as proof that Spravato prevents suicide or reduces suicidal behavior.
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Spravato is a Schedule III controlled substance and is available only through the restricted SPRAVATO REMS. The program requires supervised administration and observation. This is a safety and access condition, not an optional convenience feature.
Is ketamine FDA approved for depression?
Ketamine hydrochloride injection is FDA-labeled for anesthesia, including induction and maintenance. The FDA labeling cited here does not approve ketamine injection for depression. NIH describes subanesthetic IV ketamine used for depression as an off-label treatment: a clinician may prescribe a medicine outside its approved labeling, but that does not make the use FDA-approved.
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Off-label ketamine care does not have one universal protocol established by the sources cited here. Clinics may differ in their evaluation, administration, observation, and follow-up practices. Ask the treating clinician what the specific plan involves and what safeguards are in place.
How do the treatments compare?
| Comparison | Esketamine (Spravato) | Ketamine |
|---|---|---|
| Composition | Esketamine is the S-enantiomer of ketamine (DEA). | Racemic ketamine contains both enantiomers (DEA). |
| Depression status | FDA-labeled for the specified adult depression indications above (FDA, 2025 prescribing information). | Subanesthetic IV treatment for depression is off-label (NIH). |
| Route in the cited depression context | Intranasal spray (FDA, 2025 prescribing information). | Intravenous use in depression research; the injection product label is for anesthesia (NIH; DailyMed). |
| Administration and monitoring | Restricted SPRAVATO REMS, supervised administration, and observation (FDA; DailyMed). | A single standard protocol across off-label providers is not established by the sources cited here. |
| Which is more effective? | A universal winner is not established by the sources cited here; they do not provide an adequate head-to-head comparison. | |
What are the side effects and safety risks?
Both treatments can cause sedation and dissociation—feeling detached from oneself or one’s surroundings, or experiencing altered perception. Effects and side effects vary among people. The DEA characterizes ketamine as a dissociative drug with hallucinogenic effects; this describes a drug effect, not a predictable or uniform experience.
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Spravato safety information
FDA and DailyMed labeling warns about sedation, dissociation, respiratory depression, and abuse or misuse. It also identifies increased blood pressure and impairment in attention, judgment, thinking, reaction speed, and motor skills. The label says patients must not drive or operate machinery until the next day after a restful sleep. The supervised setting and observation requirements are intended to address risks associated with administration and its effects.
The label also calls for assessment of patients with psychosis. A prescriber can explain how individual health conditions, medicines, and blood pressure affect the treatment decision.
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What has been reported after IV ketamine?
In a 2019 report, NIH summarized short-term side-effect data from five placebo-controlled trials conducted over 13 years, involving 163 people with major depressive disorder or bipolar disorder and 25 healthy controls. The report said the most common short-term side effect after a single antidepressant dose of IV ketamine was feeling “strange or loopy,” quoting Acevedo-Diaz of the NIMH Intramural Research Program. Those study observations do not predict an individual’s experience or establish the full long-term risk profile.
Independent reader supportYour contribution helps us test, update, and keep practical guides available for everyone.Which works better for depression?
The evidence summarized here does not establish that IV racemic ketamine or intranasal esketamine is universally more effective, faster, or longer-lasting. The treatments differ in formulation, route, regulatory status, and care pathway; comparing results requires evidence that matches the patients, treatment schedules, comparison groups, and outcomes. The sources cited here do not provide an adequate direct comparison or comparative response, remission, onset, or durability figures.
A clinician can help weigh the treatment’s indication, the person’s medical history and current medicines, the required monitoring, and their preferences. Ask what outcome the proposed treatment is intended to address and how progress and side effects will be assessed.
What should you ask before considering either treatment?
- Which diagnosis and treatment goal does this option address in my case?
- Is this use FDA-labeled or off-label, and what does that mean for the proposed care?
- Where will the medicine be administered, who will supervise it, and what monitoring or follow-up is planned?
- What effects should I report, and what restrictions apply afterward?
- What will my insurer cover, and what costs should I confirm with the provider?
The sources cited here do not establish a general price, insurance-coverage rate, or access advantage for either treatment. Coverage and costs can depend on the insurer, location, provider, indication, and current rules; confirm them with the insurer and treating clinician.
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