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

Condition(s) studied

Investigational drug(s) / intervention(s)

Stimulation by the Sigma ECT/FEAST device: Titration followed by a charge applied corresponding to 6 times the seizure threshold (6xST) during the second session (first suprathreshold session). Acute treatment (week 1 à 6): FEAST/ECT sessions will take place 3 times a week. Regardless of the intervention group, the research team will recommend that treatment sessions continue until clinical remission is documented, if possible, with a maximum of 18 sessions. The consolidation phase will be carried out according to the effective parameters applied during the cure and the following tapering schedule: one session per week for one month, then one session every two weeks for two months, then one session per month for three months.

Stimulation by Sigmastim ECT 200J device administered in right unilateral (RUL): Titration followed by a charge applied corresponding to 6 times the seizure threshold (6xST) during the second session (first suprathreshold session). Acute treatment (week 1 à 6): FEAST/ECT sessions will take place 3 times a week. Regardless of the intervention group, the research team will recommend that treatment sessions continue until clinical remission is documented, if possible, with a maximum of 18 sessions. The consolidation phase will be carried out according to the effective parameters applied during the cure and the following tapering schedule: one session per week for one month, then one session every two weeks for two months, then one session per month for three months.

Stimulation by Sigmastim ECT 200J device administered in bilateral (BT): Titration followed by a charge applied corresponding to 6 times the seizure threshold (1.5xST) during the second session (first suprathreshold session). Acute treatment (week 1 à 6): FEAST/ECT sessions will take place 3 times a week. Regardless of the intervention group, the research team will recommend that treatment sessions continue until clinical remission is documented, if possible, with a maximum of 18 sessions. The consolidation phase will be carried out according to the effective parameters applied during the cure and the following tapering schedule: one session per week for one month, then one session every two weeks for two months, then one session per month for three months.

Study summary

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 conducted to date show that FEAST significantly improves depressive symptoms with a more favorable cognitive profile compared to traditional ECT, notably by reducing the impact on autobiographical memory and decreasing the time needed to regain orientation acutely after treatment. Several comparative studies between FEAST and unilateral ultra-brief pulse ECT suggest an advantage in terms of cognitive tolerance, although the differences are not always statistically significant. A multicenter trial also showed comparable effects on reducing suicidal ideation, suggesting that FEAST could be an alternative to traditional ECT. Indeed, preliminary studies indicate that FEAST may offer similar benefits to ECT in terms of reducing depressive symptoms, but with fewer cognitive side effects, which could lead to a better quality of life.

Although these studies are promising, they remain few in number and have methodological limitations (open-label clinical trials, feasibility studies, lack of randomization with a comparator arm, small sample size, or assignment to the study arm based on patient preference). There are currently no other randomized clinical trials on FEAST underway or in preparation worldwide. Well-designed, multicenter clinical trials with sufficient patient numbers to achieve satisfactory statistical power are therefore needed to address the limitations of previous studies and explore the clinical benefits of FEAST.

The present study is therefore a randomized, multicenter, double-blind clinical trial designed to evaluate the superiority of FEAST in terms of safety and efficacy compared to traditional ECT modalities.

Eligibility

Primary outcome measure(s)

• Change from baseline in the Q-LES-Q-SF score at Day 5 — From enrollment to the 5 days after the last session of the acute phase treatment (Day 5)
  Change in Q-LES-Q-SF score from inclusion to Day 5 (5 days after the last session of the acute phase treatment (Post treatment visit (D5 ± 2 days)). The total raw score ranges from 14 to 70. . The higher the score, the better the person's quality of life and self-reported satisfaction.

Trial sites (5)

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