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Effect of Repeated Intravenous Esketamine on Adolescents With Major Depressive Disorder and Suicidal Ideation: A Randomized Active-Placebo-Controlled Trial.

Yanling Zhou, Xiaofeng Lan, Chengyu Wang, Fan Zhang, Haiyan Liu, Ling Fu, Weicheng Li, Yanxiang Ye, Zhibo Hu, Ziyuan Chao, Yuping Ning

Journal of the American Academy of Child & Adolescent Psychiatry May 2024 DOI: 10.1016/j.jaac.2023.05.031 (opens in new tab)

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AI-extracted from the abstract
Characteristics Randomized controlled trial Placebo-controlled Peer reviewed
Sample size 54
Population Adolescents aged 13-18 years with major depressive disorder and suicidal ideation, recruited from an inpatient setting
Interventions Esketamine midazolam
Dose Esketamine 0.25 mg/kg; midazolam 0.02 mg/kg
Duration 3 infusions over 5 days, with assessment at day 6 and 4-week posttreatment follow-up
Measures Columbia Suicide Severity Rating Scale (C-SSRS) Ideation and Intensity, Montgomery-Åsberg Depression Rating Scale (MADRS)
Topics Depression Esketamine Ketamine
Keywords Adolescence Suicidal ideation
Key findings Three intravenous infusions of esketamine (0.25 mg/kg) over 5 days, added to routine inpatient care, reduced suicidal ideation and depression severity more than midazolam at day 6 in adolescents with major depressive disorder and suicidal ideation, and the authors report it was well tolerated. The authors characterize these as preliminary findings.

Abstract

Suicide is a major cause of death in adolescents with limited treatment options. Ketamine and its enantiomers have shown rapid anti-suicidal effects in adults with major depressive disorder (MDD), but their efficacy in adolescents is unknown. We conducted an active, placebo-controlled trial to determine the safety and efficacy of intravenous esketamine in this population. A total of 54 adolescents (aged 13-18 years) with MDD and suicidal ideation were included from an inpatient setting and randomly assigned (1:1) to receive 3 infusions of esketamine (0.25 mg/kg) or midazolam (0.02mg/kg) over 5 days, with routine inpatient care and treatment. Changes from baseline to 24 hours after the final infusion (day 6) in the scores of the Columbia Suicide Severity Rating Scale (C-SSRS) Ideation and Intensity (primary outcome) and the Montgomery-Åsberg Depression Rating Scale (MADRS, key secondary outcome) were analyzed using linear mixed models. In addition, the 4-week clinical treatment response was a key secondary outcome. The mean changes in C-SSRS Ideation and Intensity scores from baseline to day 6 were significantly greater in the esketamine group than in the midazolam group (Ideation, -2.6 [SD = 2.0] vs -1.7 [SD = 2.2], p = .007; Intensity, -10.6 [SD = 8.4] vs -5.0 [SD = 7.4], p = .002), and the changes in MADRS scores from baseline to day 6 were significantly greater in the esketamine group than in the midazolam group (-15.3 [SD = 11.2] vs -8.8 [SD = 9.4], p = .004). The rates of antisuicidal and antidepressant responses at 4 weeks posttreatment were 69.2% and 61.5% after esketamine, and were 52.5% and 52.5% after midazolam, respectively. The most common adverse events in the esketamine group were nausea, dissociation, dry mouth, sedation, headache, and dizziness. These preliminary findings indicate that 3-dose intravenous esketamine, added to routine inpatient care and treatment, was an effective and well-tolerated therapy for treating adolescents with MDD and suicidal ideation. A study to evaluate the efficacy and safety of Esketamine combined with oral antidepressants in the treatment of major depressive disorder with suicidal ideation; http://www.chictr.org.cn; ChiCTR2000041232. We worked to ensure that the study questionnaires were prepared in an inclusive way. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. We actively worked to promote sex and gender balance in our author group.

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

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