esketamin

Esketamine is the S-enantiomer of ketamine, a dissociative anesthetic. It is used as a rapid-acting antidepressant in adults with treatment-resistant depression, typically as an adjunct to a standard oral antidepressant. Esketamine is administered as a nasal spray in clinical settings under supervision.

Pharmacology and mechanism of action: Esketamine acts as a non-competitive antagonist of the NMDA receptor in the brain. By inhibiting NMDA receptor activity, it is thought to enhance glutamatergic signaling through AMPA receptors, promoting synaptic plasticity and changes in neural connectivity that may contribute to rapid mood improvement. As the more potent enantiomer of ketamine, esketamine has a distinct pharmacokinetic and pharmacodynamic profile.

Regulatory status and clinical use: In the United States, esketamine nasal spray (brand name Spravato) received FDA approval in 2019 for adults with treatment-resistant depression, to be used in addition to a traditional antidepressant. It is available only through a restricted program and must be administered in a certified health care setting with monitoring due to potential adverse effects. It is not approved as a standalone antidepressant.

Safety and monitoring: Esketamine carries boxed warnings for sedation and dissociation, transient increases in blood pressure, and risk of misuse or dependence. Common adverse effects include dizziness, nausea, and blurred vision or dissociation. Because of these risks, patients require post-dose observation, and there are cautions about activities such as driving for a period after administration.