Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent
Dong-Jing Fu, Dawn F. Ionescu, Xiang Li, Rosanne Lane, Pilar Lim, Gerard Sanacora, David Hough, Husseini Manji, Wayne C. Drevets, Carla M. Canuso
The Journal of Clinical Psychiatry May 11, 2020 DOI: 10.4088/jcp.19m13191 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 226 |
| Population | Adults with major depressive disorder, active suicidal ideation with intent, and requiring psychiatric hospitalization |
| Interventions | Esketamine nasal spray Placebo nasal spray |
| Dose | 84 mg |
| Duration | 4-week double-blind treatment |
| Topics | Depression Esketamine |
| Citations | 367 |
| Registration | NCT03039192 |
| Key findings | Esketamine plus standard care led to greater improvement in depressive symptoms at 24 hours compared to placebo plus standard care, but did not significantly reduce the severity of suicidal ideation. |
Abstract
Objective: To compare esketamine to placebo, each in addition to standard-of-care treatment, for rapidly reducing major depressive disorder symptoms, including suicidal ideation.
Methods: This phase 3, double-blind, multicenter study (ASPIRE I), conducted between June 2017 and December 2018, enrolled 226 adults having major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) criteria, active suicidal ideation with intent, and need for psychiatric hospitalization. Patients were randomized 1:1 to esketamine 84 mg or placebo nasal spray twice-weekly for 4 weeks, each with comprehensive standard-of-care treatment (initial psychiatric hospitalization and newly initiated or optimized oral antidepressant[s] therapy). Change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale (MADRS) total score (primary endpoint) was analyzed using analysis of covariance (ANCOVA), and change in Clinical Global Impression of Severity of Suicidality Revised version (CGI-SS-r; key secondary endpoint) score was analyzed using ANCOVA on ranks with treatment difference estimated using the Hodges-Lehmann estimate.
Results: Greater improvement in MADRS total score was observed with esketamine + standard-of-care versus placebo + standard-of-care at 24 hours (least-squares mean difference [SE]: -3.8 [1.39]; 95% CI, -6.56 to -1.09; 2-sided P = .006), as well as at earlier (4 hours) and later time points during 4-week double-blind treatment. The difference between groups in the severity of suicidality was not statistically significant (median of treatment difference [95% CI]: 0.0 [-1.00 to 0.00]; 2-sided P = .107). The most common adverse events among esketamine-treated patients were dizziness, dissociation, headache, nausea, and somnolence.
Conclusions: These findings demonstrate rapid and robust efficacy of esketamine nasal spray in reducing depressive symptoms in severely ill patients with major depressive disorder who have active suicidal ideation with intent.
Trial Registration: ClinicalTrials.gov identifier: NCT03039192.
In the evidence
This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.
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Esketamine plus standard care improved depressive symptoms at 24 hours versus placebo but did not significantly reduce severity of suicidal ideation.
Synthesized
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Esketamine plus standard care led to greater improvement in depressive symptoms at 24 hours compared to placebo plus standard care, but did not significantly reduce the severity of suicidal ideation.
Synthesized
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.