Real-World Safety Profile of Esketamine Nasal Spray During the First 12 Treatment Sessions: An Analysis at 58 Months After Approval in the United States

Abstract: Purpose: To examine real-world incidence of esketamine nasal spray (ESK) treatment-emergent adverse events (TEAEs) of interest (i.e., actively solicited events of sedation, dissociation, and increased blood pressure [BP]) and serious adverse events (SAEs) in the US and determine whether the rates of these events changed between induction and maintenance periods. Methods: ESK Risk Evaluation and Mitigation Strategy (REMS) patient monitoring forms from the first 58 months after US product approval (March 5, 2019–January 5, 2024) were evaluated to summarize key safety findings. This analysis focused on the induction (weeks 1-4; twice-weekly ESK dosing) and early maintenance (weeks 5-8; once-weekly ESK dosing) phases of treatment. Results: 58,483 patients had ≥1 ESK treatment session during the evaluation period. The cumulative percentage of patients who experienced ≥1 TEAE of interest during sessions 1-8 and sessions 9-12 were 55.8% and 46.2% for sedation, 61.2% and 51.2% for dissociation, 6.2% and 2.8% for increased BP, respectively. Hospitalizations occurred in ≤0.1% of patients during the first session and induction and early maintenance phases. For all treatment phases, the most common descriptions associated with SAEs were dissociation, dizziness, hypertension, increased BP, nausea, and vomiting (all 0.1%). At first treatment session, sessions 1-8, and sessions 9-12, rates of serious sedation, dissociation, and increased BP were ≤0.1%. Future analyses will include respiratory depression, which was recently added to the REMS program. Conclusion: Rates of TEAEs of sedation, dissociation, and increased BP generally decreased over the course of treatment. The overall frequency of SAEs with ESK was low.Short Description: This analysis examined real-world safety data for esketamine nasal spray (ESK) for the first 58 months after US product approval and focused on TEAEs of interest (i.e., actively solicited events of sedation, dissociation, increased blood pressure) and serious AEs during the first 12 ESK treatment sessions. Rates of sedation, dissociation, and increased blood pressure decreased over the course of treatment. Overall frequency of serious AEs with ESK was low.Name of Sponsoring Organization(s): Janssen Scientific Affairs, LLC, a Johnson & Johnson company.