Aims: To investigate real-world treatment attrition, concomitant use of pharmaceuticals with known drug-interactions, total cost of care, claims-based outcomes, and health disparities for individuals initiated on esketamine therapy in the United States. Methods: Individuals aged 18-64 with >=1 adjudicated claim for esketamine intranasal spray from 2019 to 2022 in the Optum Labs Data Warehouse (OLDW) were included. Continuous health plan enrollment was required for 6 months prior and 6 months post-esketamine start date. Medical claims, pharmacy claims data, and socioeconomic data were descriptively analyzed to investigate characteristics of the real-world esketamine cohort. Results: There were 833 individuals in the esketamine analysis cohort. 33% had <8 treatment sessions and did not finish the first stage of treatment (induction phase). Use of pharmaceuticals with drug interactions was high— 60.2% had at least one prescription fill for a drug with a known esketamine interaction in the 90-day window after esketamine initiation. Total costs of care went from $2,905 per patient per month (PPPM) in the baseline period to $5,734 PPPM in the follow-up period. Emergency department utilization with mental-health related diagnoses reduced by 42.5% in the follow-up period. PPPM utilization for office visits, excluding all claims on esketamine treatment days, went up 45% in the follow-up period. The esketamine cohort was pharmaceutically complex, and many of them had fractured care: 20% had prescription fills for >=11 drugs in the follow-up period. 18.6% percent of the cohort had >=7 drug-prescribing providers, and over 35% of the cohort had encounters with more than 10 healthcare practitioners in the follow-up period. The esketamine cohort had 26.6% more individuals in the highest socioeconomic status quintile (least socially deprived), compared to individuals with treatment-resistant depression (TRD), not initiated on esketamine. Limitations: This was a retrospective cohort descriptive analysis with small sample sizes. Additional statistical analysis was not performed. Conclusions: The esketamine cohort was characterized by considerable complexity from both a polypharmacy and lifestyle perspective. These contextual factors likely had significant bearing on adoption, access, and eventual claims-based outcomes. Understanding the interplay of these factors with the treatment dynamics of consciousness-altering compounds will be important to obtain the best real-world results from therapeutic classes with psychedelic compounds.

BT conceived of the research idea and analysis while a graduate student at University of St. Thomas and was also an employee at UnitedHealth Group and held stock in the company.

No funding was received for this research.

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Institutional Review Board of UnitedHealth Group Office of Human Research Affairs waived ethical approval for this work.

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