Subanesthetic-dose esketamine-assisted electroconvulsive therapy for suicidal ideation in adolescents with major depressive disorder: Interim trial results
Xiao-ge Han, Qibin Chen, Su Min, Bangshu Zhao, Yang Xuan-qi, Yang Hu
World Journal of Psychiatry October 21, 2026 DOI: 10.5498/wjp.124685 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, controlled trial (interim report) Longitudinal Peer reviewed |
|---|---|
| Sample size | 113 |
| Population | Adolescents aged 13-17 with major depressive disorder undergoing electroconvulsive therapy |
| Interventions | Esketamine Propofol |
| Dose | 0.25 mg/kg |
| Measures | Beck Scale for Suicide Ideation, 24-item Hamilton Depression Rating Scale, 9-item Patient Health Questionnaire, modified Positive and Negative Syndrome Scale, Montreal Cognitive Assessment |
| Topics | Depression Esketamine |
| Key findings | Adjunctive subanesthetic-dose esketamine during ECT was associated with a faster reduction in suicidal ideation and higher response rates (76.8% vs 57.9%) than saline, though remission rates were similar. Depressive and psychopathological symptoms improved and no significant short-term cognitive decline was observed; long-term outcomes remain uncertain. |
Abstract
BACKGROUNDEvidence for adjunctive subanesthetic-dose esketamine during electroconvulsive therapy (ECT) in adolescents with major depressive disorder (MDD) is limited.Suicidal ideation is a critical early treatment target in this population.We hypothesized that adjunctive subanesthetic-dose esketamine during ECT would accelerate the reduction in suicidal ideation and improve early clinical outcomes. AIMTo evaluate the efficacy and safety of adjunctive subanesthetic-dose esketamine during ECT in adolescents with MDD. METHODSThis interim report presents a randomized, double-blind, controlled trial of 113 adolescents aged 13-17 with MDD undergoing ECT.Participants were randomized 1:1 to esketamine (0.25 mg/kg) plus propofol (n = 56) or saline plus propofol (n = 57).The key outcome was early change in suicidal ideation via the Beck Scale for Suicide Ideation.Additional outcomes, including depressive and psychopathological symptoms, cognitive performance, response, remission, and safety, were also assessed.Intention-to-treat and per-protocol analyses were performed. RESULTSAdjunctive esketamine was associated with different longitudinal trajectories of suicidal ideation, with a group × time interaction (F = 95.27,P < 0.001, partial η 2 = 0.553).A higher response rate was observed in the esketamine group [76.8% vs 57.9%; adjusted odds ratio = 2.49, 95% confidence interval (CI): 1.08-5.75],although remission rates were similar.The 24-item Hamilton Depression Rating Scale scores were lower after four ECT sessions (P 4 / 43 = 0.013), while the 9-item Patient Health Questionnaire and modified Positive and Negative Syndrome Scale scores reduced during treatment (both P < 0.001).Montreal Cognitive Assessment scores were higher (adjusted mean difference = 1.24, 95%CI: 0.57-1.91,P < 0.001).Injection pain occurred less frequently (10.7% vs 33.3%, P = 0.004), with no differences in other adverse events. CONCLUSIONAdjunctive subanesthetic-dose esketamine during ECT accelerates the reduction in suicidal ideation and improves early depressive and psychopathological symptoms in adolescents with MDD.No significant short-term cognitive decline was observed; longterm outcomes remain uncertain.
Comparable studies
Other randomized controlled trials on esketamine for depression, most cited first.