Esketamine: Difference between revisions
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{{MedTemplate | {{MedTemplate | ||
| | | brand = Spravato | ||
| classes = NMDA receptor antagonist (uncompetitive), dissociative | |||
| classes | | 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 | | 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:Anesthetics]] | ||
[[Category:Arylcyclohexylamines]] | |||
[[Category:Dissociative Anesthetics]] | |||
[[Category:General (IV) Anesthetics]] | |||
[[Category:NMDA receptor antagonists]] | |||
[[Category:Antidepressants]] | |||
[[Category:Dissociatives]] | |||
Latest revision as of 05:02, 23 May 2026
NMDA receptor antagonist (uncompetitive), dissociative
Esketamine
Spravato
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.
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).
Experience
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Effects
Dissociation, sedation, dizziness, nausea, vertigo, blood pressure elevation, anxiety, sedation. Long-term risks include abuse/dependence, cognitive effects.
Pharmacodynamics
Interactions
Fluoxetine via Category:Antidepressants exp n/a/5 outcome n/a (n=1) exp 1.0/5 outcome +33.0 (n=1)
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Summary
Classes
NMDA receptor antagonist (uncompetitive), dissociative
Common 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).
Pharmacy
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)
US FDA Max
84 mg per session
Pharmacology
Routes
Intranasal (under direct medical supervision)
Onset
Within hours of first administration
Duration
Acute effect ~24 hours; cumulative effect builds with repeated dosing
Half-life
~7-12 hours
Bioavailability
~48% intranasal
Pregnancy
Avoid; may cause fetal harm
Legal status
Rx, Schedule III (US). REMS program required.
Purported 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).