esketamine

Esketamine, the S-enantiomer of ketamine, is a dissociative anesthetic with rapid-acting antidepressant effects. It is formulated as a nasal spray and approved in several countries as an adjunct to antidepressants for adults with major depressive disorder who have not responded to prior treatment (treatment-resistant depression). In some indications it is used for depressive symptoms in adults with MDD and acute suicidality, when combined with an oral antidepressant. Dosing occurs in a controlled medical setting due to risks of sedation and dissociation; it is often delivered under a REMS program.

Pharmacology: Esketamine is an NMDA receptor antagonist. By reducing NMDA activity, it triggers glutamatergic signaling that increases brain-derived neurotrophic factor (BDNF) and synaptogenesis, potentially enabling rapid mood improvements. The S-enantiomer is generally more potent at NMDA blockade than the R-enantiomer.

Administration and dosing: In practice, esketamine nasal spray is given in sessions under supervision, typically twice weekly for several weeks, then tapered. It is used in combination with a background antidepressant and is not intended as monotherapy. Individual treatment plans require monitoring for adverse effects and vital signs.

Safety and adverse effects: Common events include dissociation, dizziness, sedation, nausea, headache, and transient blood pressure increases. There is potential for misuse or diversion. Contraindications can include certain cardiovascular or intracranial conditions, and use requires careful patient selection, monitoring for suicidality, and adherence to regulatory restrictions.

Regulatory status: Esketamine nasal spray is approved in the United States and other regions for TRD and for depressive symptoms in MDD with suicidality, with a REMS program in place in some markets. Ongoing research continues to assess long-term safety and efficacy.