Real-World Safety of Esketamine Nasal Spray: A Comprehensive Analysis Almost 5 Years After First Approval.

Objective: The objective of this study was to comprehensively examine the real-world safety of esketamine using 58 months of postapproval data in the United States.

Methods: U.S. safety data from patient monitoring forms submitted to the esketamine Risk Evaluation and Mitigation Strategy (REMS) program and reports submitted to the Janssen U.S. Global Medical Safety (US-GMS) database were evaluated (March 5, 2019, to January 5, 2024). Patient characteristics, use and dosage patterns, adverse events of interest (actively solicited reports of sedation, dissociation, and increased blood pressure), and serious adverse events following esketamine administration were described. The incidence of suicidality and drug abuse/misuse was also evaluated.

Results: Most patients were 26-55 years of age (64.3%) and female (61.1%). A total of 1,486,213 outpatient treatment sessions were completed by 58,483 patients who had at least one esketamine treatment session. Sedation, dissociation, and increased blood pressure were reported in 34.7%, 41.0%, and 0.9% of sessions, respectively. Serious adverse events were reported in <0.1% and 0.18% of treatment sessions in REMS and US-GMS, respectively; suicide rates were lower than background rates; and 210 incidences of all-cause abuse/misuse were reported.

Conclusions: Analysis of almost 5 years of real-world use of esketamine in the United States remains consistent with the established safety profile from clinical studies and current product labeling. No new safety signals were identified.