REVIEW article
Front. Psychiatry
Sec. Neurostimulation
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1614076
This article is part of the Research TopicElectroconvulsive therapy: from mechanisms to clinical practiceView all 8 articles
New Insights into the Mechanisms of Electroconvulsive Therapy in Treatment-Resistant Depression
Provisionally accepted
- University of Texas Health Science Center at Houston, Houston, United States
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Electroconvulsive therapy (ECT) remains one of the most effective interventions for treatmentresistant depression (TRD), particularly in cases involving severe symptomatology, suicidality, or psychotic features. Despite advancements aimed at enhancing the safety and cognitive tolerability of ECT, concerns about cognitive side effects continue to limit its broader acceptance.A deeper understanding of the mechanisms underlying ECT is therefore critical for refining its use and maximizing clinical outcomes. Through a narrative review of recent literature, this paper synthesizes current evidence comparing the efficacy of ECT, ketamine, and repetitive transcranial magnetic stimulation (rTMS) in the treatment of TRD. Then, the review delves into the neurobiological mechanisms through which ECT exerts its therapeutic effects, including modulation of neurotransmitter systems, enhancement of neurogenesis, changes in brain network connectivity, immune response regulation, neurotrophic signaling, and epigenetic alterations.These mechanistic insights may inform the identification of biomarkers predictive of treatment response. Moving forward, future research guided by interaction mechanisms hypotheses could provide more insights into alternative neuromodulation techniques, optimize ECT procedures, and improve patient-specific treatment approaches to enhance therapeutic benefits while minimizing adverse effects.
Keywords: Electroconvulsive Therapy, Major Depressive Disorder, treatment-resistant depression, Interventional psychiatry, Neuromodulation
Received: 18 Apr 2025; Accepted: 02 Jul 2025.
Copyright: © 2025 Ruiz, Haseeb, Baumgartner, Lueng, Scaini and De Quevedo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Joao Luciano De Quevedo, University of Texas Health Science Center at Houston, Houston, United States
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