Real-World Safety of Esketamine Nasal Spray: A Comprehensive Analysis Almost 5 Years After First Approval.
Gerard Sanacora, Muhammad Ahmed, Brianne Brown, Patricia Cabrera, Teodora Doherty, M. Himedan, David M. Kern, Lisa Lim, Oliver J Lopena, R. R. Naranjo, I. Nuamah, Amir Sarayani, I. Turkoz, Hannah E Bowrey
American Journal of Psychiatry September 10, 2025 DOI: 10.1176/appi.ajp.20240655 via Semantic Scholar
Summary
Over nearly five years of real-world use in the United States, esketamine's safety profile remains consistent with clinical trial findings and product labeling. Among 58,483 patients completing 1,486,213 outpatient sessions, sedation occurred in 34.7% of sessions, dissociation in 41.0%, and increased blood pressure in 0.9%. Serious adverse events were rare, reported in less than 0.1% of sessions in the REMS program and 0.18% in the US-GMS database. Suicide rates were lower than background rates, and 210 incidences of all-cause abuse or misuse were reported. No new safety signals were identified.
Study at a glance
| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 58,483 |
| Population | Patients in the United States who had at least one esketamine treatment session |
| Keywords | Medicine |
| Citations | 24 |
| Key finding | Esketamine's real-world safety over nearly five years shows no new safety signals, with sedation and dissociation being common but serious adverse events rare. |
Abstract
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.