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Efficacy and safety of esketamine versus propofol in electroconvulsive therapy for treatment-resistant depression: A randomized, double-blind, controlled, non-inferiority trial.

Qing-Bin Zeng, De-Cheng Zou, Xing-Bing Huang, De-Wei Shang, Xiong Huang, Xin-Hu Yang, Yu-Ping Ning, Lloyd Balbuena, Yu-Tao Xiang, Wei Zheng

Journal of Affective Disorders 2025 DOI: 10.1016/j.jad.2024.09.038 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Double-blind Peer reviewed
Sample size 40
Population Patients with treatment-resistant depression
Interventions Esketamine Propofol
Duration 8 ECT sessions
Topics Depression Esketamine
Keywords Propofol Electroconvulsive therapy ect Shock therapy Electroshock Treatment-resistant depression trd Refractory depression Clinical trials rct Controlled study Medical research Anesthesia esket
Citations 12
Key findings Esketamine was non-inferior to propofol as an anesthetic for ECT in reducing depressive symptoms after eight sessions.

Abstract

Electroconvulsive therapy (ECT) is a commonly used alternative for treatment-resistant depression (TRD). Although esketamine has a rapid pharmacological antidepressant action, it has not been studied as an ECT anesthetic. The objective of this study was to compare the efficacy and safety of esketamine with propofol when both are used as ECT anesthetic agents. Forty patients with TRD were assigned to one of two arms in a double-blind, randomized controlled trial: esketamine or propofol anesthesia for a series of eight ECT sessions. Using a non-inferiority design, the primary outcome was the reduction in HAMD-17 depressive symptoms. The other outcomes were: rates of response and remission, anxiety, suicidal ideation, cognitive function, and adverse events. These were compared in an intention-to-treat analysis. Esketamine-ECT was non-inferior to propofol-ECT for reducing TRD symptoms after 8 sessions (adjusted Δ = 2.0, 95 % CI: -1.2-5.1). Compared to propofol-ECT, esketamine-ECT also had higher depression response (80 % vs. 70 %; p = .06) and remission (65 % vs. 55 %; p = .11) rates but non-inferiority was not established. In four components of cognitive function (speed of processing, working memory, visual learning, and verbal learning) esketamine-ECT was non-inferior to propofol-ECT. The results for anxiety, suicidal ideation, and adverse events (all p's > .05) were inconclusive. Esketamine was non-inferior to propofol when both are used as anesthetics for TRD patients undergoing ECT. Replication studies with larger samples are needed to examine the inconclusive results. ChiCTR2000033715.

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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