Esketamine

Esketamine, sold under the brand names Spravato (for depression) and Ketanest (for anesthesia) among others, is the S(+) enantiomer of ketamine. It is a dissociative medication used as a general anesthetic and as an antidepressant. Esketamine is the active enantiomer of ketamine in terms of NMDA receptor antagonism and is more potent than racemic ketamine. However, racemic ketamine may produce larger and more sustained antidepressant effects than esketamine. As an anesthetic, esketamine is indicated for high-risk patients or as a supplement to incomplete regional anesthesia. As an antidepressant, it is specifically used as both a monotherapy and combination therapy for treatment-resistant depression (TRD) as well as major depressive disorder (MDD) with co-occurring suicidal ideation or behavior. Its efficacy as combination therapy for TRD is modest and similar to that of atypical antipsychotics; evidence for its efficacy as a monotherapy is very limited. Antisuicidal efficacy remains unproven. Esketamine is not used by infusion into a vein for depression as it is only FDA-approved in the form of a nasal spray under direct medical supervision for this indication (the parent compound ketamine is most often administered intravenously). Adverse effects of esketamine include dissociation, dizziness, sedation, nausea, vomiting, vertigo, numbness, anxiety, lethargy, increased blood pressure, and feelings of drunkenness. Less often, esketamine can cause bladder problems. Esketamine acts primarily as a NMDA receptor antagonist. Esketamine has faster clearance and stronger dopamine inhibition than arketamine, contributing to its dissociative and psychotomimetic effects. In the form of racemic ketamine, esketamine was first synthesized in 1962 and introduced for medical use as an anesthetic in 1970. Enantiopure esketamine was introduced for medical use as an anesthetic in 1997 and as an antidepressant in 2019. It is used as an anesthetic in the European Union and as an antidepressant in the United States and Canada. Due to...