Public opinion on electroconvulsive therapy (ECT) remains largely negative, as reflected in social media content on platforms such as X (formerly known as Twitter). ^{Reference de Anta, Alvarez-Mon, Donat-Vargas, Lara-Abelanda, Pereira-Sanchez and Gonzalez Rodriguez1} As professionals, it is our role to challenge outdated misconceptions and provide up-to-date information in a digestible format for patients and carers. This letter outlines recent advances in our understanding of how ECT works and its implications for various neuropsychiatric conditions.

ECT is a safe and vital intervention for various psychiatric conditions, including severe depression, catatonia and clozapine-resistant schizophrenia. ^{Reference Fink2} Historically, ECT evolved from early shock therapies of the 1930s into a more refined procedure involving anaesthesia and muscle relaxants by the 1940s. The introduction of psychoactive drugs in the 1950s further modified ECT parameters, although stigma persisted, particularly during the antipsychiatry movements of the 1980s and 1990s. ^{Reference Medda, Perugi, Zanello, Ciuffa and Cassano3}

The mechanism of ECT remains incompletely understood; however, contemporary research demonstrating neurochemical and anatomical changes provides important insight. The efficacy of ECT is linked to its ability to induce seizures that temporarily disrupt brain function, leading to physiological changes and enhanced neuroplasticity. These effects have been associated with increased brain tissue volume and improved neural connectivity, both of which may contribute to symptom improvement. By contrast, excessive electrical field exposure may increase cognitive adverse effects, whereas insufficient dosing may reduce therapeutic benefit. Recent research has explored several hypotheses to explain the mechanism of action.

1. (a) Amnesia hypothesis: initially, amnesia was considered to be therapeutic. It was posited that memory loss of the symptoms of mental illness and of the events preceding these symptoms would ‘erase’ the mental illness itself. However, later treatments in the 1930s demonstrated that the treatment efficacy of ECT was not correlated with the degree of amnesia. It is now understood that the electrical field exposure primarily drives side-effects including memory loss, whereas seizure activity drives efficacy. ^{Reference Miller4,Reference Rosenman5}

2. (b) Anticonvulsant hypothesis: this theory posits that the effect of ECT is mediated by a postictal inhibitory surge in regions of the prefrontal cortex, which leads to termination of a seizure and enhances GABAergic function. Evidence supporting this theory includes observed increases in seizure threshold and its correlation with decreasing depressive symptoms. In the prefrontal cortex specifically, both high-dose right unilateral and bitemporal ECT modalities induce seizures and produce comparable increases in seizure threshold, as well as similar reductions in depressive symptoms. ^{Reference Rosenman5} By contrast, low-dose right unilateral ECT induces seizures in the motor cortex, lacks antidepressant efficacy and results in minimal changes in seizure threshold. However, reproducibility of the correlation between seizure threshold and antidepressant response has been inconsistent. Moreover, magnetic resonance spectroscopy investigations of GABA concentration during ECT have reported either no significant alterations or increases that show no consistent association with antidepressant outcomes. Furthermore, studies show no change in plasma concentration of neuroactive steroids, which modulate GABA receptor function, before and after ECT. ^{Reference Baghai, di Michele, Schüle, Eser, Zwanzger and Pasini6} Thus, the anticonvulsant hypothesis alone is insufficient to explain the mechanism of ECT.

3. (c) Neurogenesis hypothesis: in addition to the postictal inhibitory surge, the therapeutic effects of ECT are theorised to depend on increases in numbers of neurons and interconnections among neurons. Animal models of ECT demonstrate neurotrophic effects in rodents with increases in synaptic proteins, granule cells and cells in the dentate gyrus, and increased signalling of brain-derived neurotrophic growth factor and vascular endothelial growth factor. Notably, epileptic seizures induce similar neurogenic effects without electrical stimulation, suggesting that the seizure itself and not the electrical field exposure drives treatment efficacy. However, even though brain-derived neurotrophic growth factor increases post-ECT, no clear relationship between this increase and change in depressive symptoms has been established. In addition, evidence shows that neurotrophic changes in the medial temporal lobes are required for sustained remission. ^{Reference Baghai, di Michele, Schüle, Eser, Zwanzger and Pasini6} Alongside this, the frontal lobe inhibitory surge and subsequent reductions in metabolism and perfusion are key to an acute response.

4. (d) Neuroplastic changes: magnetic resonance imaging studies show increased hippocampal volume post-ECT. However, this change in volume seems unrelated to antidepressant effect or adverse cognitive effects and is transient. There is a smaller body of literature on ECT induced neuroplasticity in regions other than the hippocampus, highlighting the need for increased research in this area. Increased functional connectivity between the medial prefrontal cortex and the ventrolateral prefrontal cortex, and between the dorsomedial prefrontal cortex and posterior cingulate cortex, have been linked to improved therapeutic outcomes. ^{Reference Takamiya, Bouckaert, Laroy, Blommaert, Radwan and Khatoun7} This illustrates the role of neuroplastic changes caused by ECT in driving treatment efficacy.

5. (e) Role of electric field and seizure expression: the strength of the electric field to which the hippocampus is exposed has a positive linear relationship with its volume increase; this is negatively correlated with change in antidepressant outcomes. ^{Reference Oltedal, Narr, Abbott, Anand, Argyelan and Bartsch8} Therefore, although hippocampal volume mediates the relationship between electrical field and antidepressant response, it does so in a manner that supresses the direct effect of the electrical field. This suggests that seizures with no hippocampal electrical field exposure (such as those induced through magnetic seizure therapy and individualised low-amplitude seizure therapy) could separate the impact of the electrical field from the neuroplastic effects of seizures. ^{Reference Francis-Taylor, Ophel, Martin and Loo9}

Our evolving understanding of how this powerfully effective treatment works, and how to minimise adverse effects associated with it, will help to shape the direction of neuropsychiatric research, as well as fostering a more informed and balanced view of its role in psychiatric care.