(213) An Assessment of Use and Emerging Safety of Esketamine Nasal Spray in the U.S., 2019-2023

Background: The U.S. Food and Drug Administration approved Spravato™ (esketamine, nasal spray) in 2019 for treatment-resistant depression, in conjunction with an oral antidepressant. The Spravato REMS (Risk Evaluation and Mitigation Strategy) is intended to ensure safe administration of the nasal spray in a healthcare setting with patient monitoring after administration given concerns over sedation, dissociation, and abuse/misuse. Assessment of esketamine use and safety in the real-world setting is warranted.

Objectives: To characterize the use of esketamine nasal spray in the U.S. and investigate any potential adverse events using a self-controlled design with tree-based scan statistics on U.S. administrative claims data

Methods: New users of esketamine were identified from 2019 through 2023 in U.S. PharMetrics administrative claims data. The retrospective cohort of new users was descriptively characterized by age group, gender, geographic region, history of depression, and psychiatric medication use. Signal detection was performed using tree-based scan statistics on the hierarchical ICD-10 coding tree across all coding levels, using only incident events occurring in any care setting. A self-controlled tree temporal scan analysis using TreeScan™ software compared the occurrence of any ICD-10 diagnosis code in all combinations of risk windows to control windows in the 30-day period following esketamine initiation. Test statistics were maximum log likelihood ratios (LLRs) calculated for each node and branch, generating p-values that serve as signaling thresholds (p < 0.05).

Results: A total of 1,273 new users of esketamine were identified in Pharmetrics between 2019 and 2023, with use increasing over time. Users were predominantly female (61.4%), over 40 years of age (63.7%), and resided in either the southern (48.8%) or midwestern (25.4%) U.S.. Nearly 85% of users were dispensed an antidepressant and 44.5% were dispensed dispensed an antipsychotic in the 90 days before esketamine use. The proportion of esketamine users with a dispensing for an antidepressant in days 1-90, 91-180, and 181-270 post-esketamine use were 96.0%, 72.6%, and 57.0%, respectively, while dispensing of antipsychotics occurred in 41.3%, 33.7%, and 28.0% of new esketamine users, respectively. Only 1 safety alert was detected among esketamine users- “Other and unspecified disorders of nose and nasal sinuses” (LLR=7.1, p< 0.02, risk window: days 8-11).

Conclusions: Descriptive analyses suggest patients are initiating esketamine in the U.S. as indicated in the label and that antidepressant use is decreasing in the months following esketamine initiation. Only 1 potential safety alert was detected in the 30 days following first use, which may warrant further exploration.