Accelerated TMS for Treatment-Resistant ECT

Electroconvulsive therapy (ECT) is a well-established and effective treatment for severe major depressive disorder. However, a significant proportion of patients do not achieve remission after ECT, and effective follow-up treatment options for these non-responders remain limited.

This phase IV study explores the clinical effectiveness of an additional course of accelerated deep transcranial magnetic stimulation (dTMS) in patients who show partial or no response to ECT. The accelerated dTMS protocol consists of 20 sessions delivered over four consecutive days.

All patients initially undergo standard ECT treatment, accompanied by comprehensive psychological testing, clinical assessments, functional MRI scans (pre- and post-ECT), and collection of blood and stool samples. These data will be used to evaluate treatment response and investigate biological correlates of treatment outcomes, such as microbiome composition and genetic biomarkers.

Patients who do not reach remission after state-of-the-art ECT will be offered the opportunity to participate in the interventional phase of the study, receiving accelerated dTMS treatment, followed by a third fMRI scan and additional clinical, psychological testing, and biological sampling.

The primary goal is to assess whether this additional dTMS treatment improves remission rates. Secondary goals include evaluating brain-based, genetic, and gut-related predictors of treatment response, with the aim of guiding more personalized treatment strategies in the future.

Inclusion criteria

• Diagnosis of Major Depressive Disorder (MDD)
• Age between 18 - 70 years
• Referred for ECT treatment

Exclusion criteria

• A personal history of seizures or epilepsy, a history of seizures or epilepsy in first degree relatives and the presence of any known factor that can lower the seizure threshold (sleep deprivation, abuse substance, etc.), previous head injury and the presence of metallic implants in the cephalic region (e.g., aneurysm clips, shunts, stimulators, cochlear implants, electrodes) except dental fill-ings and the presence of cardiac pacemakers, neurostimulators, surgical clips or other electronic equipment, comorbidity with some neurological disorders: increased intracranial pressure, space-occupying lesion, history of stroke or transient ischemic attack, brain aneurysm and any structural brain damage with increased risk for epilepsy detected with MRI
• Patients with cognitive disturbances or dementia (Mini Mental State) < 24
• Suicide attempt within 6 months before the start of the study or pre-sent risk of suicide per the investigator's clinical judgment