Real-World Safety Profile of Esketamine Nasal Spray During the First 12 Treatment Sessions: An Analysis at 46 Months After Approval in the United States

This work was sponsored by Janssen Scientific Affairs, LLC Purpose: To examine real-world incidence of esketamine nasal spray (ESK) treatment-emergent adverse events (TEAEs) of interest (i.e., sedation, dissociation, increased blood pressure [BP]) and serious adverse events (SAEs) in the United States, and to determine if the rates of these events change between induction and maintenance periods. Methods: ESK Risk Evaluation and Mitigation Strategy patient monitoring forms were evaluated to summarize key safety findings for the first 46 months (March 5, 2019, to January 5, 2023) after US product approval, with a focus on induction (weeks 1-4 of treatment with twice-weekly ESK dosing) and maintenance (weeks 5-8 of treatment with once-weekly ESK dosing) periods. Results: A total of 34,110 patients had ≥1 ESK treatment session during the evaluation period. The cumulative percentage of patients who experienced ≥1 TEAEs of interest during sessions 1-8 and sessions 9-12 were 58.4% and 48.2% for sedation, 62.7% and 52.6% for dissociation, and 6.5% and 3.1% for increased BP, respectively. Hospitalizations occurred in 0.2% of patients (first session, 0.1%; sessions 1-8, 0.1%; sessions 9-12, 0.1%). For all treatment phases, the most common (≥0.2%) descriptions associated with SAEs were nausea, vomiting, and increased BP. At first treatment session, sessions 1-8, and sessions 9-12, descriptions for sedation, dissociation, and increased BP were present in ≤0.1% of SAE reports. Conclusion: Rates of TEAEs of sedation, dissociation, and increased BP generally decreased over time. The overall frequency of SAEs with ESK was low and no new safety signals were identified.