TOPLINE:

The 5-year “real-world” safety profile of esketamine nasal spray for depression was consistent with prior clinical trial data, with most adverse events (AEs) being transient and serious AEs observed in less than 0.2% of all treatment sessions, new research showed.

METHODOLOGY:

• Researchers analyzed safety data for more than 58,000 individuals (64% aged 26-55 years; 61% women) who underwent nearly 1.5 million outpatient treatment sessions with esketamine between 2019 and 2024.
• The data were collected from the Risk Evaluation and Mitigation Strategy (REMS) program, which was developed by manufacturer Janssen Pharmaceuticals on the basis of FDA requirements, and from Janssen’s US Global Medical Safety (US-GMS) database.
• The treatment phases included induction (sessions 1-8), early maintenance (sessions 9-12), and late maintenance (sessions 13 and beyond).
• The primary outcomes included incidence of AEs (sedation, dissociation, and elevated blood pressure) and serious AEs. The incidence of suicidality and drug abuse or misuse was also evaluated.

TAKEAWAY:

• At least one AE occurred in 51% of treatment sessions, with sedation reported in 35%, dissociation in 41%, and increased blood pressure in 1% of sessions.
• The incidence of sedation was highest during the first esketamine session, followed by the induction and early maintenance phases (39 vs 37 vs 35 per 100 administrations, respectively), as was the incidence of dissociation (46.9 vs 43.5 vs 41.2 per 100 administrations) and increased blood pressure (1.6 vs 1.2 vs 0.9 per 100 administrations).
• Serious AEs occurred in less than 0.1% of sessions in the REMS database and in 0.18% of sessions in the US-GMS database. The rate of serious AEs was highest during the first esketamine session (0.3%), followed by the induction (0.1%) and early maintenance (< 0.1%) phases.
• The incidence of completed suicide was 0.18 per 100 patient-years. A total of 210 cases of potential drug abuse or misuse were reported, and the estimated incidence of death was 0.6 per 100 patient-years.

IN PRACTICE:

“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,” the investigators wrote, adding that they did not identify any new safety signals.

SOURCE:

The study was led by Gerard Sanacora, MD, PhD, Yale Depression Research Program, Yale University, New Haven, Connecticut. It was published online on September 10 in The American Journal of Psychiatry.

LIMITATIONS:

The study was limited by the occasional presence of illegible or missing fields in REMS patient monitoring forms. Solicited reporting may have led to an overestimation of sedation and dissociation events, and reporters may not have been fully trained in Good Clinical Practice guidelines. Efficacy outcomes were also not assessed, and discrepancies between REMS and US-GMS data, including potential duplicates in the US-GMS database, may have affected comparisons.

DISCLOSURES:

The research was supported by Janssen Scientific Affairs, a Johnson & Johnson company. Sanacora reported receiving several financial relationships, including research grants or contracts from Johnson & Johnson/Janssen. The other investigators are current or former employees of Johnson & Johnson. Full details are listed in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.