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esketamine

Adjunctive therapy

Brand: Spravato

Published 2026-03-18 · Last reviewed 2026-03-25 · 5 references

Content sourced from FDA labeling (DailyMed) and peer-reviewed literature.

Print sheet Review evidence

At a glance

Class: Adjunctive therapy·Typical dose: Administration occurs under direct observation in a certified healthcare setting with post-dose monitoring for at least 2 hours (label/REMS).·Half-life: Single-dose range 7–12 h·LAI available: No

Class: Adjunctive therapy
Typical dose: Administration occurs under direct observation in a certified healthcare setting with post-dose monitoring for at least 2 hours (label/REMS).
Half-life: Single-dose range 7–12 h
LAI available: No

Quick answers

What is esketamine?: Esketamine (brand Spravato) is an intranasal antidepressant option used under a REMS program for treatment-resistant depression (TRD) in adults (as monotherapy or in conjunction with an oral antidepressant) and for depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant (label).
What is Spravato?: Spravato is a brand name for esketamine.
What is Spravato (esketamine) used for?: Label indications include: Treatment-resistant depression in adults (as monotherapy or with an oral antidepressant); depressive symptoms in adults with MDD with acute suicidal ideation or behavior (with an oral antidepressant); REMS-restricted (label).
What drug class is Spravato (esketamine)?: NMDA Antagonist.
What is the mechanism of action of Spravato (esketamine)?: Intranasal NMDA receptor antagonist (esketamine) used under a REMS for treatment-resistant depression (as monotherapy or with an oral antidepressant) and depressive symptoms in MDD with acute suicidal ideation/behavior (with an oral antidepressant); administered in a certified healthcare setting due to sedation, dissociation, respiratory depression, and abuse/misuse risk.
What strengths does Spravato (esketamine) come in?: Nasal spray device: 28 mg esketamine per device; 56 mg dose uses two devices and 84 mg dose uses three devices (label).
What is the maximum dose of Spravato (esketamine) for major depressive disorder (clinical depression)?: Depressive symptoms with MDD and acute suicidal ideation/behavior: 84 mg twice weekly for 4 weeks (may reduce to 56 mg based on tolerability); benefit beyond 4 weeks is not established in trials for this indication (label).

General information

Esketamine (Spravato) is an intranasal antidepressant option used under a REMS program for treatment-resistant depression (as monotherapy or with an oral antidepressant) and for depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior (with an oral antidepressant) (label).

Administration is supervised in a certified healthcare setting because sedation, dissociation, and respiratory depression can occur; the label requires post-dose monitoring for at least 2 hours (label).

Transient blood pressure increases are common; blood pressure monitoring before and after dosing is part of routine safety checks (label).

Esketamine is a controlled substance and carries an abuse and misuse warning; screening for substance use history and ongoing monitoring are common parts of practice (label/clinical).

The esketamine compare view, evidence feed, and print page help compare side-effect profiles and implementation logistics.

U.S. approvals

Treatment-resistant depression (with an oral antidepressant; REMS program) (2019)
Depressive symptoms in MDD with acute suicidal ideation or behavior (with an oral antidepressant; REMS program) (2020)
Treatment-resistant depression as monotherapy (REMS program) (2025)

Formulations & strengths

Nasal spray device: 28 mg esketamine per device; 56 mg dose uses two devices and 84 mg dose uses three devices (label).
Dose kits commonly correspond to 56 mg and 84 mg total doses (label).

Generic availability

Not available generically (brand-only).

Esketamine is a high-resource intervention due to REMS certification requirements, on-site administration, required post-dose monitoring, and same-day driving restrictions. Access and scheduling capacity often shape use as much as clinical need (label/clinical).

View labelExact

Mechanism of action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Esketamine is the S-enantiomer of ketamine and acts as an NMDA receptor antagonist. Its antidepressant effect is commonly framed in terms of downstream glutamatergic and synaptic plasticity changes rather than monoamine reuptake inhibition (label/clinical).

Rapid symptom improvement can occur in some patients. For TRD, esketamine may now be used as monotherapy or with an oral antidepressant; structured follow-up and monitoring remain required (label/clinical).

NMDA receptor antagonism (primary pharmacologic activity).
Downstream glutamatergic signaling changes (clinical framing).

Metabolism & pharmacokinetics

Esketamine is primarily metabolized to noresketamine via CYP2B6 and CYP3A4 and to a lesser extent CYP2C9 and CYP2C19; subsequent metabolites undergo glucuronidation (label).
After intranasal administration, plasma concentrations decline biphasically with a mean terminal half-life range of ~7 to 12 hours (label).
Esketamine and major metabolites generally do not show strong CYP inhibition potential; modest induction of CYP2B6 and CYP3A4 is described in human hepatocytes (label).

Dosing & administration

Administration occurs under direct observation in a certified healthcare setting with post-dose monitoring for at least 2 hours (label/REMS).
Treatment-resistant depression (adults): Induction is twice weekly for 4 weeks (56 mg or 84 mg), then once weekly for weeks 5–8 (56 mg or 84 mg), then every 2 weeks or once weekly for maintenance based on response (label).
Depressive symptoms with MDD and acute suicidal ideation or behavior: 84 mg twice weekly for 4 weeks (may reduce to 56 mg twice weekly based on tolerability); benefit beyond 4 weeks is not established for this indication (label).
The nasal spray device delivers 28 mg; 56 mg uses two devices and 84 mg uses three devices with a rest between devices during administration (label).
The label advises avoiding food for at least 2 hours and liquids for at least 30 minutes before dosing to reduce nausea/vomiting risk (label).

Monitoring & labs

Observe for sedation and dissociation for at least 2 hours after dosing, with assessment of clinical stability before discharge (label/REMS).
Respiratory status monitoring during the post-dose window (including pulse oximetry) (label).
Blood pressure checks before dosing and during post-dose observation (label).
Abuse/misuse risk screening and ongoing monitoring (label/clinical).
Suicidal thoughts and behaviors monitoring during treatment changes (label).

Adverse effects

FDA boxed warnings

Sedation, dissociation, and respiratory depression risk; monitoring for at least 2 hours after each dose is required (REMS/label).
Abuse and misuse risk (controlled substance); careful patient selection and monitoring are required (REMS/label).
Suicidal thoughts and behaviors warning for antidepressants; close monitoring is typical during treatment changes (label).

Common side effects (≥10%)

Dissociation: Common shortly after dosing; typically monitored during the required observation period (label).
Sedation / somnolence: Can occur after dosing; same-day driving restrictions and observation requirements reflect this risk (label).
Increased blood pressure: Transient increases are expected; monitoring before and after dosing is typical (label).
Nausea / vomiting: May be reduced by avoiding food for 2 hours and liquids for 30 minutes before dosing (label).
Dizziness / vertigo: Can occur during the post-dose window; fall-risk counseling is common (clinical).

Other notable effects

Cognitive and psychomotor impairment can occur after dosing; same-day driving restrictions are part of standard counseling (label).
Contraindications include aneurysmal vascular disease, arteriovenous malformation, and history of intracerebral hemorrhage (label).
Blood pressure-related symptoms (chest pain, severe headache, vision changes, seizures) prompt urgent evaluation (label).

Interactions

Additive sedation with alcohol, benzodiazepines, opioids, and other CNS depressants; medication reconciliation is common before initiation (label/clinical).
Psychostimulants and MAOIs can increase blood pressure; closer monitoring is typical when combinations are unavoidable (label).
Esketamine metabolism involves CYP2B6 and CYP3A4; interaction review is prudent in complex regimens with strong inducers or inhibitors, even though major inhibition effects are not a dominant feature (label/clinical).

Other useful information

A structured treatment setting is part of the therapy: certified site administration, post-dose monitoring, and documentation requirements are integral to risk mitigation (REMS/label).
Esketamine is typically paired with an oral antidepressant and reassessment of benefit after induction is common, particularly when symptom improvement is modest (label/clinical).
Same-day transportation planning is required because driving and hazardous activities are restricted after treatment sessions (label).

References

Related hubs:SMI toolkit·Support resources