Esketamine: Difference between revisions

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{{MedTemplate

| ~~generic~~ ~~= Esketamine~~

| brand = Spravato

~~| brand~~ = Spravato

| classes = NMDA receptor antagonist (uncompetitive), dissociative

| classes = ~~Dissociative~~, ~~Anesthetic, Antidepressant~~

| mechanism = The S-enantiomer of racemic ketamine. Uncompetitive NMDA receptor antagonist (binds open channel). Proposed antidepressant mechanism: NMDA blockade on GABA interneurons disinhibits glutamate burst → AMPA receptor activation → BDNF/VEGF release → mTOR-mediated synaptogenesis and dendritic spine formation within hours. Also binds sigma-1, opioid receptors (controversial μ-opioid contribution to antidepressant effect debated).

| mechanism = NMDA receptor antagonist (S-enantiomer of ketamine)

| uses = Treatment-resistant depression (TRD) in adults, as adjunct to oral antidepressant (FDA-approved March 2019). Depressive symptoms in adults with MDD with acute suicidal ideation or behavior (FDA-approved Aug 2020).

| starting_dose = Induction (TRD): 56 mg intranasal twice weekly × 4 weeks. Maintenance: 56-84 mg once weekly × 4 weeks, then 56-84 mg every 1-2 weeks. For acute suicidality: 84 mg twice weekly × 4 weeks. Administered under medical supervision in REMS-certified site.

| preparations = 28 mg/device (each dose uses 2 devices)

| fda_max = 84 mg per session

| routes = Intranasal (under direct medical supervision)

| onset = Within hours of first administration

| duration = Acute effect ~24 hours; cumulative effect builds with repeated dosing

| halflife = ~7-12 hours

| bioavailability = ~48% intranasal

| pregnancy = Avoid; may cause fetal harm

| legal = Rx, Schedule III (US). REMS program required.

| intro = '''Esketamine''' (brand name Spravato) is the S-enantiomer of ketamine, FDA-approved as an intranasal medicine for treatment-resistant depression (March 2019) and for major depression with acute suicidal ideation or behavior (August 2020). The S-enantiomer has approximately 4-fold higher NMDA receptor affinity than the R-enantiomer; Spravato delivers it via a nasal spray under direct medical supervision in a REMS-certified setting due to risks of dissociation, sedation, and abuse.

Mechanism: uncompetitive NMDA receptor antagonism on GABA interneurons disinhibits glutamatergic output, leading to AMPA receptor activation, BDNF/VEGF release, and rapid synaptogenesis through mTOR pathway activation. Antidepressant onset within hours is striking compared to monoaminergic antidepressants (4-6 weeks). Patients must be monitored ≥2 hours after dose due to dissociation, sedation, and blood pressure elevation.

| pharmacodynamics= Uncompetitive NMDA receptor antagonist with channel-trapping action. Sigma-1 receptor binding. Possible weak μ-opioid agonism (mechanism contribution debated; naltrexone-blockade studies have given conflicting results).

| effects = Dissociation, sedation, dizziness, nausea, vertigo, blood pressure elevation, anxiety, sedation. Long-term risks include abuse/dependence, cognitive effects.

| interactions = <pharmaInteractions/>

}}

[[Category:Anesthetics]]

[[Category:Arylcyclohexylamines]]

[[Category:Dissociative Anesthetics]]

[[Category:General (IV) Anesthetics]]

[[Category:NMDA receptor antagonists]]

[[Category:Antidepressants]]

[[Category:Dissociatives]]

CategoryClaude (talk | contribs)