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Effect of esketamine and etomidate anesthesia on neuroplasticity in electroconvulsive therapy for treatment-resistant depression.

Guo-Guang Zhao, Jing Zhao, Yan Kong, Ya-Ping Pang, Xiao-Nan Zheng, Yi-Wei Zhang

World Journal of Psychiatry September 19, 2025 DOI: 10.5498/wjp.v15.i9.109458 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Randomized controlled trial Peer reviewed
Sample size 120
Population Patients with treatment-resistant depression treated at the Department of Psychiatry, The Second Affiliated Hospital of Shandong First Medical University, China, between April 2020 and April 2024
Interventions Esketamine Etomidate Electroconvulsive therapy (ECT)
Measures Heart rate (HR), mean arterial pressure (MAP), peripheral capillary oxygen saturation (SpO2), initial and final threshold charges, serum brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), 5-hydroxytryptamine (5-HT), interleukin-4 (IL-4), BRNAS, Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), Hamilton Depression Rating Scale (HAMD)-24, Wisconsin Card Sorting Test, Tower of Hanoi test
Topics Depression Esketamine Neuroplasticity
Keywords Neurological function Etomidate Electroconvulsive therapy Executive function
Key findings Adding esketamine to etomidate anesthesia during ECT for treatment-resistant depression was associated with more stable vital signs, lower final and total seizure threshold charges, higher post-treatment BDNF, NGF, 5-HT, and IL-4 levels, and better scores on BRNAS, MCCB, HAMD-24, the Wisconsin Card Sorting Test, and the Tower of Hanoi compared with etomidate alone, with no difference in adverse reactions.

Abstract

Background: Treatment-resistant depression (TRD) has a poor response to clinical treatment. Patients with TRD do not respond adequately to standard antidepressants. Even after receiving a full dose and sufficient duration of combined antidepressant therapy, significant improvement is still difficult to achieve. At present, electroconvulsive therapy (ECT) remains a clinically effective method for treating refractory depression. A good anesthesia regimen can enhance its clinical efficacy. Actively exploring high-quality anesthesia regimens has become a current research hotspot.

Aim: To explore the effect of esketamine and etomidate anesthesia on the clinical efficacy of ECT for TRD.

Methods: A total of 120 patients with TRD, treated at the Department of Psychiatry, The Second Affiliated Hospital of Shandong First Medical University, China between April 2020 and April 2024, were selected for the study. The patients were allocated at random into two groups using a random number table: The combination and control groups, with 60 patients in each group. Both groups underwent ECT; the combination group received esketamine and etomidate anesthesia, while the control group received etomidate anesthesia. The following parameters were compared between the two groups: Heart rate (HR); mean arterial pressure (MAP); peripheral capillary oxygen saturation (SpO2); initial and final threshold charges; and serum brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), 5-hydroxytryptamine (5-HT), and interleukin-4 (IL-4) levels. Neurological functions, basic executive function scores, and adverse reactions were compared during the treatment process.

Results: During treatment, the maximum and minimum HR and MAP values in the combination group were markedly lower than those in the control group (P < 0.05), whereas there was no significant difference in SpO2 between the two groups (P > 0.05). During the treatment, there were no significant differences in the initial threshold charge and average duration of seizures during ECT between the two groups (P > 0.05). However, the final threshold charge and total charge in the combination group were considerably lower than those in the control group (P < 0.05). After treatment, the BDNF, NGF, 5-HT, and IL-4 levels were evidently higher in the combination group than in the control group (P < 0.05). During treatment, as the number of ECT sessions increased, both BRNAS and Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) scores increased, whereas Hamilton Depression Rating Scale (HAMD)-24 scores decreased in both groups. Starting from the third treatment session, the BRNAS and MCCB scores in the combination group were higher than in the control group, whereas the Hamilton Depression Scale-24 score was lower in the combination group than in the control group (P < 0.05). After treatment, the Wisconsin Card Sorting Test scores and Tower of Hanoi test results in the combination group were significantly better than those in the control group (P < 0.05). The occurrence of adverse reactions was compared between the two groups (P > 0.05).

Conclusion: Esketamine and etomidate anesthesia during ECT for patients with TRD helps maintain stable vital signs during the treatment process, improves depressive symptoms, and enhances neurological and basic executive functions.

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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