Long-Term Safety and Maintenance of Response With Esketamine Nasal Spray in Participants With Treatment-Resistant Depression: Interim Results of the SUSTAIN-3 Study.

In an open-label extension study of adults with treatment-resistant depression, long-term intermittent intranasal esketamine combined with an oral antidepressant maintained improvements in depression ratings. Among 1,148 participants, mean Montgomery-Åsberg Depression Rating Scale scores decreased during the 4-week induction phase and remained stable during optimization/maintenance, with 35.6% and 46.1% of participants in remission at the respective endpoints. Common side effects included headache, dizziness, nausea, dissociation, somnolence, and nasopharyngitis. No new safety signal emerged over up to 4.5 years of treatment, supporting sustained efficacy and tolerability for this population.

Study at a glance

Abstract

Patients with treatment-resistant depression (TRD) have higher rates of relapse and pronounced decreases in daily functioning and health-related quality of life compared to patients with major depressive disorder who are not treatment-resistant, underscoring the need for treatment choices with sustained efficacy and long-term tolerability. Adults with TRD who participated in ≥1 of 6 phase 3 "parent" studies could continue esketamine treatment, combined with an oral antidepressant, by enrolling in phase 3, open-label, long-term extension study, SUSTAIN-3. Based on their status at parent-study end, eligible participants entered a 4-week induction phase followed by an optimization/maintenance phase, or directly entered the optimization/maintenance phase of SUSTAIN-3. Intranasal esketamine dosing was flexible, twice-weekly during induction and individualized to depression severity during optimization/maintenance. At the interim data cutoff (01 December 2020), 1148 participants were enrolled, 458 at induction and 690 at optimization/maintenance. Mean (median) cumulative duration of maintenance esketamine treatment was 31.5 (37.7) months (totaling 2769 cumulative patient-years). Common treatment-emergent adverse events (≥20%) were headache, dizziness, nausea, dissociation, somnolence, and nasopharyngitis. Mean Montgomery-Åsberg Depression Rating Scale (MADRS) total score decreased during induction, and this reduction persisted during optimization/maintenance (mean [SD] change from the baseline to the endpoint of each phase: induction -12.8 [9.73]; optimization/maintenance +1.1 [9.93]), with 35.6% and 46.1% of participants in remission (MADRS total score ≤12) at induction and optimization/maintenance endpoints, respectively. Improvement in depression ratings generally persisted among participants who remained in maintenance treatment, and no new safety signal was identified during long-term treatment (up to 4.5 years) using intermittent-dosed esketamine in conjunction with daily antidepressant. Appeared originally in Neuropsychopharmacology 2023; 48: 1225-1233.