Safety and Efficacy with Esketamine in Treatment-Resistant Depression: Long-Term Extension Study
Chen, L. N., Doherty, T., Drevets, W. C., Fu, D. J., Lacerda, A. L. T., Lane, R., Morrison, R. L., Paik, J.-W., Popova, V., Sanacora, G., Wilkinson, S. T., Young, A. H., Zaki, N.
This Phase III open-label extension study (n=1148) evaluates the long-term safety and efficacy of esketamine nasal spray combined with oral antidepressants in treatment-resistant depression (TRD) patients who previously participated in other Phase III trials. The study involved flexible dosing of intranasal esketamine (twice-weekly during induction, then weekly to monthly during maintenance) with direct staff supervision, with participants either entering through a 4-week induction phase (n=458) or directly into maintenance (n=690) based on their previous response.
Abstract
Importance The rates of relapse and suicide risk are higher in treatment-resistant depression (TRD) versus non-treatment-resistant major depressive disorder. Even among patients with TRD who initially respond, the majority (70%) relapse within 6 months.Objective To evaluate the long-term safety and efficacy of esketamine nasal spray, combined with an oral antidepressant, in patients with TRD.Design Phase 3, open-label, single-arm long-term extension study (SUSTAIN-3) conducted from June 2016 to December 2022Setting OutpatientParticipants Adults with TRD who participated in ≥1 of 6 phase 3 “parent” studies continued esketamine by either entering a 4-week induction phase followed by an optimization/maintenance phase of variable duration (n=458), or directly entering the optimization/maintenance phase of SUSTAIN-3 (n=690), based on their individual response to study drug at the endpoint of the parent study.Interventions Intranasal esketamine dosing was flexible, twice-weekly during induction and individualized to depression severity during optimization/maintenance (weekly, every-other-week, or every-4-weeks), under direct supervision by site staff.Main Outcomes and Measures To assess long-term safety of esketamine. Efficacy endpoint included change in depressive symptoms, assessed by Montgomery-Åsberg Depression Rating Scale (MADRS).