Pharmacology Corner: Esketamine (Spravato)-A New Novel Medication to Treat Depression-But With a Strong Warning.

Esketamine (Spravato), a nasal spray formulation of the NMDA receptor antagonist ketamine, was approved by the FDA in March 2019 for treatment-resistant depression in adults, to be used alongside an oral antidepressant. About one third of patients with major depressive disorder are treatment resistant to current antidepressants, and depression in bipolar disorder also responds poorly to them. Esketamine must be administered under direct healthcare provider supervision, with blood pressure monitoring before and after dosing, and patients observed for at least 2 hours. To reduce nausea and vomiting, patients should avoid food for 2 hours and liquids for 30 minutes before administration.

Study at a glance

Abstract

Treatment resistant depression is a common and burdensome condition with poor outcomes and few treatment options. Approximately one third of patients with major depressive disorder are treatment resistant to the current antidepressants. In addition, depression in patients with bipolar disorder is typically poorly responsive to antidepressants. And so, there is an unmet need for rapidly acting antidepressants in those treatment-resistant patients with either major depressive disorder or bipolar disorder. Currently, the most commonly used oral antidepressants are thought to treat depression by increasing levels of neurotransmitters (serotonin, norepinephrine, and dopamine) in areas of the brain that affect mood. Research evidence suggests that N-methyl-D-aspartate (NMDA) receptor antagonism produces antidepressant effects (Stahl, 2013). Ketamine, an NMDA antagonist, is a racemic mixture comprising equal parts of R-ketamine (arketamine) and S-ketamine (esketamine). Because S-ketamine has a higher affinity for the NMDA receptor, esketamine was developed as an antidepressant, and in March 2019, esketamine nasal spray was approved by the U. S. Food and Drug Administration for use in conjunction with an oral antidepressant for the treatment of treatment-resistant depression in adults (Hashimoto, 2019). Esketamine is marketed by Janssen under the trade name Spravato. It is a Schedule III medication and is formulated as a nasal spray. There are multiple restrictions that may affect time management for the provider. The medication must be administered under the direct supervision of a healthcare provider, and postadministration observation is also required. Before administration, blood pressure must be assessed. After dosing, blood pressure is reassessed at approximately 40minutes and subsequently as clinically warranted. If blood pressure is decreasing and the patient appears clinically stable for at least 2 hours, the patientmay be discharged at the end of the postdose monitoring period. Because some patients may experience nausea and vomiting after administration of Spravato, the patient should be advised to avoid food for at least 2 hours and avoid liquids for at least 30 minutes prior to administration.