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Short-term cognitive effects of repeated-dose esketamine in adolescents with major depressive disorder and suicidal ideation: a randomized controlled trial

Xiaofeng Lan, Chengyu Wang, Fan Zhang, Haiyan Liu, Weicheng Li, Yanxiang Ye, Zhibo Hu, Siming Mai, Yuping Ning, Yanling Zhou

Child and Adolescent Psychiatry and Mental Health September 14, 2023 DOI: 10.1186/s13034-023-00647-2 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Sample size 51
Population Adolescents aged 13-18 with major depressive disorder and suicidal ideation
Interventions Esketamine Midazolam
Dose Esketamine 0.25 mg/kg; Midazolam 0.02 mg/kg
Duration Three infusions; assessments at Days 0, 6, and 12
Measures MATRICS Consensus Cognitive Battery (MCCB)
Topics Depression Esketamine Ketamine
Citations 22
Key findings Three-dose subanesthetic esketamine infusions did not harm cognition in adolescents with MDD and suicidal ideation; esketamine was associated with improvement in processing speed from baseline to Days 6 and 12 and in working memory from baseline to Day 12. Baseline cognition was not significantly associated with antidepressant or antisuicidal effects.

Abstract

Background: Ketamine and its enantiomer have rapid and robust effects on depressive symptom and suicidal ideation. Little is known about their cognitive effects in adolescents. We aimed to evaluate the short-term effect of esketamine on cognition in adolescents with major depressive disorder (MDD) and suicidal ideation.

Method: In this randomized-controlled trial, 51 participants aged 13-18 with MDD and suicidal ideation received three intravenous infusions of either esketamine (0.25 mg/kg) or midazolam (0.02 mg/kg). Four dimensions of the MATRICS Consensus Cognitive Battery (MCCB), including processing speed, working memory, verbal learning and visual learning, were assessed at Days 0, 6 and 12.

Results: In the linear mixed model, a significant time main effect (F = 12.803, P < 0.001), drug main effect (F = 6.607, P = 0.013), and interaction effect (F = 3.315, P = 0.041) was found in processing speed. Other dimensions including working memory and verbal learning showed significant time main effect (all P < 0.05), but no significant drug or interaction effect (all P > 0.05). Esketamine group showed improvement in processing speed from baseline to Days 6 and 12, and working memory from baseline to Day 12 (all P < 0.05). The generalized estimation equation showed no significant association between baseline cognition and antidepressant or antisuicidal effect (both P > 0.05).

Conclusions: The present study suggested that three-dose subanesthetic esketamine infusions did not harm cognition among adolescents with MDD and suicidal ideation. Instead, esketamine may be associated with improvement in processing speed.

Trial Registration: This trial was registered in the Chinese Clinical Trials Registry ( http://www.chictr.org.cn , ChiCTR2000041232).

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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