Long-Term Safety 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 safety of esketamine nasal spray (ESK) in adults with treatment-resistant depression (TRD) dosed according to US prescribing information. Methods: Safety 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 entered SUSTAIN-3 in either the IND or OP/M. 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. Results: A total of 1021 patients were included in this analysis. The median (max) duration of ESK treatment was 46.9 (79) months. Among included patients, 440 (43.1%) entered the study at IND and 581 (56.9%) entered at OP/M. During the combined IND and OP/M phases, 967 patients (94.7%) experienced a treatment-emergent adverse event (TEAE). The most common (>20%) TEAEs were headache (37.4%), dizziness (34.7%), nausea (34.4%), dissociation (26.4%), somnolence (23.6%), nasopharyngitis (23.0%), and dysgeusia (21.6%). Most TEAEs were mild or moderate in severity and resolved on the same day as dosing. A total of 4 patients (0.9%) in the IND phase and 180 patients (18.3%) in the OP/M phase experienced ≥1 serious AE. Conclusion: Results from this subgroup analysis were consistent with the established safety and tolerability profile, with no new safety signals identified, for long-term treatment (up to 6.5 years) with flexibly-dosed ESK in adults with TRD.