esketamine

General information

• Class: Adjunctive therapy
• Common US brands: Spravato
• Typical dose range: Administration occurs under direct observation in a certified healthcare setting with post-dose monitoring for at least 2 hours (label/REMS).
• Therapeutic drug monitoring not routinely recommended.
• Last reviewed: 2026-03-25

Dosing & forms

• Forms/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).
• Frequency: 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).
• Typical range: Administration occurs under direct observation in a certified healthcare setting with post-dose monitoring for at least 2 hours (label/REMS).

Mechanism (brief)

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.

Metabolism & Half‑life

• Metabolism: CYP2B6, CYP3A4, CYP2C9, CYP2C19
• Half‑life: Single-dose range 7–12 h

Therapeutic Drug Monitoring (TDM)

Recommended: No

Monitoring highlights

• 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).

Sources

• 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)
• AGNP TDM Consensus — Pharmacopsychiatry (2018)
• APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)
• FDA approves SPRAVATO (esketamine) as monotherapy for treatment-resistant depression in adults — Janssen Pharmaceuticals (2025)