Introduction: Efficacy and safety of esketamine (ESK) nasal spray were evaluated in ASPIRE-2 (NCT03097133), one of two phase-3 studies in the first global registration program in an understudied population of patients with major depressive disorder (MDD) at imminent risk for suicide.
Methods: In this double-blind (DB), multicenter study, patients (18-64 years) with MDD (DSM-5 criteria), active suicidal ideation with intent, and requiring psychiatric hospitalization were eligible. Patients were randomized (1:1) to ESK (84 mg) or placebo nasal spray twice-weekly along with comprehensive standard-of-care (SoC) for 4 weeks. Efficacy: change from baseline to 24-hours after first-dose in Montgomery-Ǻsberg Depression Rating Scale (MADRS) total score (primary endpoint) and Clinical Global Impression- Severity of Suicidality–Revised (CGI-SS-R; key secondary endpoint). Safety was monitored.
Results: Of 230 randomized patients, 227 (mean age: 40.8 years) received either ESK+SoC (n=114) or placebo+SoC (n=113); 184/230 (80%) completed DB treatment. Baseline mean MADRS total score was 39.7 and 91% of patients were moderately-extremely suicidal (CGI-SS-R). Patients receiving ESK+SoC showed significant improvement in MADRS total score over placebo+SoC at 24-hours after first dose (LS-mean [SE] difference: −3.9 [1.39]; p=0.006). Although improvement in CGI-SS-R was observed in both treatment groups, between group difference was not significant. During the double-blind phase the most common adverse events in the ESK+SoC group were dizziness (41%), dissociation (39%), nausea (33%) and dysgeusia (25%).
Conclusions: ESK+SoC showed rapid reduction in depressive symptoms in vulnerable MDD patients who have active suicidal ideation with intent. Safety profile was consistent with earlier ESK studies.
This poster was presented at the 32nd annual Psych Congress, held Oct. 3-6, 2019, in San Diego, California.