Long-Term Efficacy of Esketamine Nasal Spray Dosed in Accordance With US Prescribing Information in Adults With Treatment-Resistant Depression: A Subgroup Analysis of the SUSTAIN-3 Study Up to 6.5 Years

This work was sponsored by Janssen Scientific Affairs, LLC Purpose: To describe long-term efficacy of esketamine nasal spray (ESK) in adults with treatment-resistant depression (TRD) dosed according to US prescribing information. Methods: Efficacy data were drawn from SUSTAIN-3 (NCT02782104), a phase 3, open-label long-term extension study composed of 2 phases: a 4-week induction phase (IND) and a variable-duration optimization/maintenance phase (OP/M). This subgroup analysis included adults (aged 18-64 years) who previously participated in 1 of 5 ESK “parent” studies and then entered SUSTAIN-3. In addition to an oral antidepressant (OAD), patients received ESK 56 or 84 mg twice weekly during IND and flexibly-dosed ESK during OP/M. Clinician- and patient-reported disease severity were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS) and Patient Health Questionnaire 9-item (PHQ-9). Changes in efficacy outcomes are summarized descriptively. Results: A total of 1021 patients were included in this analysis. The median (max) duration of ESK treatment was 46.9 (79) months. At the beginning of IND, mean baseline MADRS and PHQ-9 were 29.1 and 15.4, respectively (consistent with moderate-to-severe disease). During the 4-week IND, mean (SD) changes from baseline in MADRS and PHQ-9 total scores were −12.9 (9.67) and −5.9 (5.77), respectively. These improvements were maintained over OP/M. The proportion of patients who achieved MADRS and PHQ-9 remission (defined as