esketamine

Adjunctive therapy

Brands: Spravato

Last reviewed 2025-12-30

Reviewed by PsychMed Editorial Team.

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Quick answers

What is esketamine?
Esketamine (brand Spravato) is an intranasal antidepressant option used under a REMS program for treatment-resistant depression and for depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior, always 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 (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)?
Intranasal NMDA receptor antagonist (esketamine) used under a REMS for treatment-resistant depression and depressive symptoms in major depressive disorder (MDD) with acute suicidal ideation/behavior; 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).

Snapshot

Class: Adjunctive therapy
Common US brands: Spravato
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2025-12-30

Label indications

Treatment-resistant depression in adults (with an oral antidepressant); depressive symptoms in adults with MDD with acute suicidal ideation or behavior (with an oral antidepressant); REMS-restricted (label).

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Clinical Highlights

Esketamine (brand Spravato) is an intranasal antidepressant option used under a REMS program for treatment-resistant depression and for depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior, always in conjunction with an oral antidepressant (label). Because sedation, dissociation, and respiratory depression can occur, dosing happens in a certified healthcare setting and patients are monitored for at least 2 hours after each treatment session (label).

Esketamine has abuse and misuse risk (it is a controlled substance), so screening for substance use history and ongoing monitoring are common parts of practice (label/clinical).
Transient increases in blood pressure are expected in many patients; blood pressure checks before dosing and during the post-dose observation window are typical (label).
The compare view, esketamine evidence feed, and esketamine print page help contextualize benefit, logistics, and side-effect trade-offs.

Dosing & Formulations

Esketamine is supplied as a 28 mg nasal spray device; 56 mg uses two devices and 84 mg uses three devices, with a short rest between devices during administration (label). 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/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).
To reduce nausea and vomiting, the label advises avoiding food for at least 2 hours and liquids for at least 30 minutes before dosing (label).
Esketamine is administered under direct observation and is not dispensed for home use (label/REMS).

Monitoring & Risks

Post-dose monitoring for sedation and dissociation is required; the label calls for observation for at least 2 hours with assessment of clinical stability before discharge (label). Respiratory status monitoring (including pulse oximetry) is recommended during the post-dose window because respiratory depression has been reported (label).

Blood pressure increases can occur and may last several hours; urgent evaluation is typical if severe symptoms occur (e.g., chest pain, shortness of breath, severe headache, vision changes, seizures) (label).
Same-day driving and hazardous activities are restricted after treatment sessions; transportation planning is part of practical counseling (label).
Contraindications include aneurysmal vascular disease, arteriovenous malformation, and history of intracerebral hemorrhage (label).

Drug Interactions

Additive sedation can occur with alcohol, benzodiazepines, opioids, and other CNS depressants; medication reconciliation of sedating co-therapies is common before starting esketamine (label/clinical). Concomitant psychostimulants or MAOIs can further raise blood pressure; closer monitoring is typical when combinations are necessary (label).

Esketamine is metabolized primarily via CYP2B6 and CYP3A4 (and to a lesser extent CYP2C9/2C19); interaction review is prudent in complex regimens that include strong inducers or inhibitors (label/clinical).

Practice Notes

Esketamine’s limiting factor is often logistics: twice-weekly visits early in treatment, on-site monitoring, and day-of-driving restrictions. Feasibility can drive selection as much as symptom severity (clinical). For treatment-resistant depression, clinicians commonly define a response target and reassess benefit after the induction phase rather than continuing indefinitely without objective improvement (label/clinical).

Continued oral antidepressant therapy and attention to psychotherapy, sleep, and substance use supports remain part of the overall care plan even when esketamine is added (APA/clinical).

References

SPRAVATO (esketamine) nasal spray prescribing information — DailyMed (2025)
Efficacy AND Safety OF Flexibly Dosed Esketamine Nasal Spray Combined With A Newly Initiated Oral Antidepressant IN Treatment Resistant Depression: A Randomized Double Blind Active Controlled Study — American Journal of Psychiatry (2019)
APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)