How electroconvulsive therapy works in the treatment of depression: is it the seizure, the electricity, or both?

Abstract

We have known for nearly a century that triggering seizures can treat serious mental illness, but what we do not know is why. Electroconvulsive Therapy (ECT) works faster and better than conventional pharmacological interventions; however, those benefits come with a burden of side effects, most notably memory loss. Disentangling the mechanisms by which ECT exerts rapid therapeutic benefit from the mechanisms driving adverse effects could enable the development of the next generation of seizure therapies that lack the downside of ECT. The latest research suggests that this goal may be attainable because modifications of ECT technique have already yielded improvements in cognitive outcomes without sacrificing efficacy. These modifications involve changes in how the electricity is administered (both where in the brain, and how much), which in turn impacts the characteristics of the resulting seizure. What we do not completely understand is whether it is the changes in the applied electricity, or in the resulting seizure, or both, that are responsible for improved safety. Answering this question may be key to developing the next generation of seizure therapies that lack these adverse side effects, and ushering in novel interventions that are better, faster, and safer than ECT.

Effects of electroconvulsive therapy on cortical thickness in depression: a systematic review

“…Although most increases were observed near the placement of the electrodes, temporal changes were also observed when the electrodes were located in the frontal lobe (Xu et al, 2019;Ji et al, 2022). Despite decades of use, the precise mechanisms by which ECT exerts its therapeutic effects remain poorly understood (Fridgeirsson et al, 2021;Deng et al, 2023). Among the hypotheses of ECT action, three main theories have been proposed: the generalised seizure theory, the neuroendocrine-diencephalic theory, and a combined anatomical-ictal theory (Bolwig, 2011).…”

Electroconvulsive therapy increases cortical thickness in depression: A systematic review

“…This may be a consequence of the increased expression and release of brain-derived neurotrophic factor induced by ECT (Polyakova et al, 2015), which could ultimately be the basis for the therapeutic efficacy of ECT. However, whether the efficacy of ECT is related to the electric field or the resulting seizure, or both, remains a debated matter (Deng et al, 2023). The temporal lobe plays a crucial role in the pathophysiology of depression, as it is involved in the core neuropsychological features that are commonly disrupted in MDD and bipolar depression, including emotional processing and social cognition (Gillissie et al, 2022;Takahashi et al, 2010).…”

Electroconvulsive Therapy Modulates Loudness Dependence of Auditory Evoked Potentials: A Pilot MEG Study

“…These include, but are not limited to, changes in neurotransmitter transmission, enhancement of neurotrophic and neuroplastic activities, modulation of cortical networks, reduction of neuroinflammation, and regulation of the endocrine system. (3, 4, 5, 6, 7, 8, 9, 10). Given the historical precedence of the monoaminergic theory of depression, a plethora of studies in both animals and humans have sought out to determine whether ECT’s efficacy is related to changes in serotonergic activity (11, 12).…”