Sustained Response to Esketamine Nasal Spray in Patients With Treatment-Resistant Depression: Analysis of Long-Term Data from the SUSTAIN-2 Study

Abstract: Background: This post hoc analysis of SUSTAIN-2 (NCT02497287), an open-label, long-term safety and efficacy study of esketamine nasal spray (ESK), assessed sustained response (SR) to ESK in combination with an oral antidepressant (OAD) in adults with treatment-resistant depression (TRD). Methods: Adults who completed the 4-week induction phase (IND) and entered the 48-week optimization/maintenance phase (OP/M) with ≥8 weeks of exposure in OP/M were included. Patients received ESK 56 mg or 84 mg twice weekly during IND and flexible dosing during OP/M (both in combination with an OAD). Definitions of SR were based on the Montgomery- Åsberg Depression Rating Scale (MADRS), 9-item Patient Health Questionnaire (PHQ-9), Clinical Global Impression-Severity Scale (CGI-S), and the Sheehan Disability Scale (SDS); SR was assessed between weeks 4 and 48 during OP/M. Results: The analysis included 440 patients. Mean (SD) baseline MADRS, PHQ-9, SDS, and CGI-S total scores were 31.1 (4.67), 17.7 (4.58), 22.2 (4.82), 4.9 (0.71), respectively. The percentages of patients with SR to ESK from weeks 4 to 48 (weeks 3 to 47 for PHQ-9) were 85.4%, 79.6%, 65.3%, and 95.7%, respectively. The most common (≥20%) TEAEs were dizziness (37.3%), headache (34.6%), dissociation (32.1%), and nausea (30.9%); 1 patient (0.2%) in IND and 28 patients (6.4%) in OP/M experienced ≥1 serious AE. Conclusion: Depending on assessment used, 65%-96% of patients were considered as having a SR to ESK treatment over a 48-week period. Results were consistent with the established tolerability profile of ESK; no new safety signals were identified.Short Description: In a post hoc analysis of SUSTAIN-2 (NCT02497287), an open-label, long-term safety and efficacy study of esketamine nasal spray (ESK), sustained response to ESK in combination with an oral antidepressant was observed in 85.4%, 79.6%, 65.3%, and 95.7% of patients after 48 weeks of treatment as determined per MADRS, PHQ-9, SDS, and CGI S assessments, respectively. Results of this analysis were consistent with the established tolerability profile of ESK. No new safety signals were identified.Name of Sponsoring Organization(s): Janssen Scientific Affairs, LLC