Evaluating the Therapeutic Potential of Focal Electrically Administered Seizure Therapy (FEAST) in the Treatment of Depression: A Multicenter Randomized Clinical Trial

A significant proportion of patients remain resistant to antidepressant therapies, even when treatment is well managed. Electroconvulsive therapy (ECT) is a well-established method for treating certain severe and resistant psychiatric pathologies. ECT is also the gold standard for treating mood disorders. Although effective, it is associated with cognitive side effects (memory impairment, post-ECT confusion, longer reorientation time), particularly with bitemporal (BT) montage and brief pulse stimulation. These effects may contribute to patient reluctance and limit adherence to this therapy. From a mechanistic point of view, ECT causes changes in cerebral blood flow (rCBF) and brain electrical activity, particularly in the prefrontal cortex, where the induction of "pseudo-epileptic seizures" appears to be related to therapeutic efficacy, while cognitive side effects appear to be associated with alterations in the temporal areas. The conventional stimulation method results in widespread diffusion of the current due to the properties of the skull, limiting control over the distribution of intracerebral charge densities. In this context, a new approach called "Focal Electrically Administered Seizure Therapy" (FEAST) has been developed to focus the electrical current and limit cognitive side effects. Unlike traditional ECT, FEAST uses unidirectional current and optimized electrode placement, aiming to induce seizures in a more localized manner in the right prefrontal cortex while reducing propagation to temporal regions. The FEAST configuration is based on scientific literature (protocols, parameters, electrode positioning) and not on a "pre configured" mode validated by the medical device manufacturer. Neuroimaging studies suggest that FEAST causes an increase in blood flow in the right prefrontal cortex at the onset of the seizure, followed by a postictal redistribution similar to that observed with ECT, confirming its targeted effect. Open-label clinical trials con