Patients with major depressive disorder (MDD) having active suicidal ideation with intent require immediate treatment.
This double-blind study (ASPIRE II) randomized adults (aged 18-64 years) with MDD having active suicidal ideation with intent to esketamine 84 mg or placebo nasal spray twice-weekly for 4 weeks, given with comprehensive standard-of-care (hospitalization ≥5 days and newly-initiated or optimized oral antidepressant[s]). Change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale (MADRS) total score (primary efficacy endpoint) was analyzed using analysis of covariance (ANCOVA). Clinical Global Impression-Severity of Suicidality – revised (CGI-SS-r; key secondary endpoint) was analyzed using ANCOVA on ranks of change.
Of 230 patients who were randomized (115 per arm), 227 received study drug and were included in efficacy/safety analyses; 184 (80.0%) completed double-blind treatment. Greater improvement in MADRS total score was observed with esketamine (mean [SD]: -15.7 [11.56]) versus placebo (-12.4 [10.43]), each with standard-of-care, at 24 hours (least-squares, LS, mean difference [SE]: -3.9 [1.39], 95% CI: -6.60, -1.11; 2-sided p=0.006). This was also noted at the earlier (4-hour) timepoint (LS mean difference -4.2, 95% CI: 6.38, 1.94). Patients in both treatment groups experienced rapid reduction in CGI-SS-r; the between-group difference was not statistically significant. The most common adverse events among esketamine-treated patients were dizziness, dissociation, nausea, dysgeusia, somnolence, headache, and paresthesia.
This study confirmed rapid and robust reduction of depressive symptoms with esketamine nasal spray in severely ill patients with MDD who have active suicidal ideation with intent.
Clinical Trials.gov identifier: NCT03097133.
© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.