Esketamine
Spravato
NMDA Receptor AntagonistSchedule IIIGeneric available
Esketamine, the S-enantiomer of racemic ketamine, is a non-selective, non-competitive antagonist of the N -methyl- D -aspartate (NMDA) receptor, an ionotropic glutamate receptor. The mechanism by which esketamine exerts its antidepressant effect is unknown. The major circulating metabolite of esketamine (noresketamine) demonstrated activity at the same receptor with less affinity.
Compare Esketamine →FDA-Approved Indications
- Treatment-resistant depression — mono or with oral antidepressant (adults)
- MDD with acute suicidal ideation/behavior — with oral antidepressant (adults)
Common Off-Label Uses
- Chronic pain (subanesthetic)
- Acute suicidality in non-MDD conditions
What Sets This Drug Apart
- S-enantiomer of ketamine; only FDA-approved NMDA antagonist nasal spray for treatment-resistant depression (TRD) and MDD with acute suicidal ideation/behavior
- REMS-mandated: must be administered in certified healthcare settings with 2-hour post-dose monitoring; cannot be taken home
- Rapid onset antidepressant effect (within hours to days) — fundamentally different time course from all traditional antidepressants (weeks)
- Dissociative side effects are frequent and expected (perceptual changes, depersonalization); peak ~30 min post-dose, resolve within 2 hours
- Schedule III controlled substance; must be co-prescribed with an oral antidepressant (not approved as monotherapy)
Boxed Warning
WARNING: SEDATION