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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)

Relevant Not relevant

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.

  • State of the evidence: Esketamine for depression Supports

    Esketamine plus standard care improved MADRS scores more than placebo at 24 hours (LS mean difference -3.8) but did not significantly reduce severity of suicidal ideation.

    Synthesized

  • State of the evidence: Esketamine Mixed

    Esketamine plus standard care led to greater improvement in depressive symptoms at 24 hours than placebo plus standard care, but did not significantly reduce severity of suicidal ideation.

    Synthesized

Comparable studies

Other randomized controlled trials on esketamine for depression, most cited first.

Study Year Design Participants
Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study Adults with moderate to severe nonpsychotic depression and a history of nonresponse to... 2019 Phase 3, double-blind, active-controlled, multicenter randomized controlled trial n = 227
Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression Adults with treatment-resistant depression who achieved stable remission or stable... 2019 Phase 3, multicenter, double-blind, randomized withdrawal study n = 297
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression Adults with DSM-IV-TR diagnosis of major depressive disorder and history of inadequate... 2017 Phase 2, double-blind, doubly randomized, delayed-start, placebo-controlled study n = 67
Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study Depressed patients at imminent risk for suicide 2018 Randomized controlled trial n = 68
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1) Adults with moderate-to-severe depression and nonresponse to at least two... 2019 Randomized controlled trial n = 346

Citations in the library

Cited by 113

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