INTRODUCTION: Treatment-resistant depression (TRD) is related to disproportionate unemployment and productivity burden in the USA. The current study describes real-world mental health (MH)-related disability days and costs of patients with TRD initiated on esketamine nasal spray or conventional therapies in the USA. METHODS: Adults with TRD were selected from Merative™ MarketScan RESULTS: The study comprised four cohorts: esketamine (n = 107
mean age: 45.5 years, female: 54.2%), ECT (n = 55
mean age: 47.6 years, female: 41.8%), TMS (n = 443
mean age: 46.1 years, female: 57.3%), and SGA (n = 4374
mean age: 44.8 years, female: 59.1%). In month 6 pre-index, mean number of MH-related disability days was 1.7 in the esketamine cohort, 1.2 in the TMS cohort, 1.3 in the ECT cohort, and 0.8 in the SGA augmentation cohort
mean MH-related disability costs were US 43 in the esketamine cohort, US 39 in the TMS cohort, US 78 in the ECT cohort, and US 43 in the SGA augmentation cohort. In all cohorts, a peak in mean MH-related disability days and costs was observed 1 month after therapy initiation followed by a decreasing trend. In month 6 post-index versus month 6 pre-index, the mean number of MH-related disability days trended lower in the esketamine cohort (- 0.4 days), remained the same in the TMS cohort and largely the same in the SGA augmentation cohort (+ 0.1 days), and trended higher (+ 1.6 days) in the ECT cohort. In the same timeframe, MH-related disability costs trended lower in the esketamine and TMS cohorts, with observed reductions of US 12 and US 23, respectively. Costs remained largely the same in the SGA augmentation cohort (+ US 6), and trended higher (+ US 53) in the ECT cohort. CONCLUSIONS: In this descriptive study, initiation of esketamine was associated with trends toward lower MH-related disability days and costs. Conventional therapies demonstrated varied patterns, with no consistent trend toward reductions in disability days across all therapies and no observed cost-savings trends for SGA augmentation and ECT. These trends suggest potential economic and societal gains of esketamine treatment for TRD but warrant further investigation with larger samples and robust statistical comparisons.