Barriers to Esketamine Nasal Spray Treatment Among Adults With Treatment-Resistant Depression

Background: Under a risk evaluation and mitigation strategy program, esketamine nasal spray CIII requires self administration at a certified treatment center. Our objective was to identify factors associated with esketamine initiation and continuation.Methods: A retrospective observational cohort study was conducted among US adults who met treatment-resistant depression (TRD) criteria. Cases (n = 966) initiated esketamine between October 11, 2019, and February 28, 2022, and were compared to controls (n = 39,219) with TRD but no esketamine use. Outcomes included initiation, induction (8 administrations within 45 days), and interruptions (30-day treatment gap). Comorbid psychiatric conditions were identified using International Classification of Diseases, Tenth Revision, Clinical Modification, codes.Results: Cases resided significantly closer to treatment centers (8.9 vs 20.3 miles). Compared to 0-9 miles, initiation rate decreased by 11.9%, 50.8%, 68.1%, 75.9%, and 92.8% for individuals residing 10-19, 20-29, 30-39, 40-49, and 50+ miles from a center. After adjustment, factors associated with increased likelihood of initiation were posttraumatic stress disorder, major depressive disorder with suicidal ideation, and male sex, while increasing distance, substance use disorder, Medicaid, Charlson Comorbidity Index (CCI), and older age were associated with lower likelihood. Factors associated with lower likelihood of completing induction were Medicaid, low socioeconomic status (SES), CCI, and Hispanic communities. Factors associated with increased likelihood of interruption were alcohol use disorder, distance, and minority communities, while generalized anxiety disorder and Medicaid were associated with lower likelihood.Conclusions: Travel distance, insurance, low SES, and minority communities are potential barriers to treatment. Alternative care models may be needed to ensure adequate access to care.