What Is Spravato?

Both names refer to the same product. Patients will see “Spravato” on clinic paperwork and “esketamine” in insurance documents and medical literature.

Ketamine as a molecule exists in two mirror-image forms, called enantiomers. Racemic ketamine — the form used in anesthesia and in off-label infusion treatment — contains both. Esketamine is only the S-form. [FDA label]

The practical distinctions matter more than the chemistry. Spravato has FDA-approved labeling for specific depression indications, a defined dosing schedule, and a mandatory safety program. Racemic ketamine is FDA-approved as an anesthetic; its use for depression is off-label, meaning it is prescribed outside the indications on its approved label. Off-label prescribing is legal and common in medicine, but it means the FDA has not reviewed and approved that specific use.

A fuller side-by-side comparison, including route, monitoring, and coverage, is in Spravato vs. IV ketamine.

The FDA-approved labeling lists two indications, both in adults:

• Treatment-resistant depression (TRD) in adults, as monotherapy or in conjunction with an oral antidepressant. [FDA label] The monotherapy option was added by FDA supplement approval on January 17, 2025. [FDA approval letter]
• Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior, in conjunction with an oral antidepressant. [FDA label]

Limitations of use stated in the labeling

The label attaches explicit limits to the second indication, and these matter:

• The effectiveness of Spravato in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated. [FDA label]
• Use of Spravato does not remove the need for hospitalization when hospitalization is clinically warranted.
• Spravato is not approved as an anesthetic agent.

In other words, the approval for that indication concerns depressive symptoms — not a demonstrated effect on suicide risk itself. Anyone in immediate danger needs emergency care, not an outpatient appointment.

Who fits these indications in practice is covered in Who qualifies for Spravato.

The prescribing information describes esketamine as a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, a receptor in the glutamate system. It also states plainly that the mechanism by which esketamine exerts its antidepressant effect is unknown. [FDA label]

That distinction is worth keeping. The receptor pharmacology is established; the causal chain from that pharmacology to symptom change is not. Explanations involving neuroplasticity or synaptic changes are active areas of research rather than statements in the approved labeling, and this page does not present them as settled.

Spravato is supplied in single-use nasal spray devices. The patient self-administers the spray under the direct observation of a healthcare provider — a 56 mg dose uses two devices and an 84 mg dose uses three, with a five-minute rest between devices. [FDA label]

The labeling also gives specific timing instructions before a dose:

• Avoid food for at least 2 hours before administration.
• Avoid liquids for at least 30 minutes before administration.
• If a nasal corticosteroid or nasal decongestant is needed, take it at least 1 hour before Spravato.

What a visit looks like start to finish is described in what to expect at your first appointment, and the dosing schedule over time is in how often treatment is given.

A Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program the FDA can require when a medication’s risks need managing beyond ordinary prescribing. Spravato is available only through the Spravato REMS, because of the risks of sedation, dissociation, respiratory depression, and abuse and misuse. [FDA label]

Under the program, the labeling specifies that Spravato is:

• dispensed and administered only in certified healthcare settings, with patients in outpatient settings enrolled in the program;
• administered by the patient under the direct observation of a healthcare provider, who then monitors the patient for at least two hours;
• dispensed by certified pharmacies only to certified healthcare settings.

The program is explained in more detail in what is the Spravato REMS program.

After each dose, patients are monitored by a healthcare provider for at least two hours, and are then assessed for clinical stability before they leave. [FDA label] Two hours is a minimum, not a fixed length: monitoring continues until the clinician judges the patient stable for discharge.

The monitoring period exists because of effects that are expected and timed:

• Blood pressure increases peak roughly 40 minutes after administration and last about four hours, so blood pressure is checked before the dose and again around 40 minutes afterward. [FDA label]
• Sedation and dissociation are most pronounced shortly after dosing and are observed until they resolve.
• Respiratory status, including pulse oximetry, is monitored during the period.

There is no take-home supply of Spravato. The REMS requirements limit dispensing and administration to certified healthcare settings, and certified pharmacies may ship only to those settings. [SPRAVATO REMS] The medication stays in the clinic; the patient comes to it.

Two consequences follow for scheduling. Every dose is an appointment of at least a couple of hours, and every appointment requires a way home that isn’t driving yourself — the labeling instructs patients not to drive or operate machinery until the next day after a restful sleep. [FDA label]

Spravato is esketamine nasal spray, given in a certified healthcare setting under observation. Its labeling covers treatment-resistant depression in adults, with or without an oral antidepressant, and depressive symptoms in adults with major depressive disorder and acute suicidal ideation or behavior, with an oral antidepressant. It is closely related to ketamine but is a separate, separately regulated product.

The requirements that define the treatment experience — in-office administration, at least two hours of monitoring, no driving until the next day, and no take-home supply — come from the FDA-approved labeling and the REMS program, not from any individual clinic’s policy.