Clinical, thinking, and brain effects of adding repetitive magnetic stimulation to electroconvulsive therapy in hard-to-treat depression: a blinded, multi-center trial
Eighty patients with will be evaluated in a trial assessing the impact of on outcomes.
Approximately one-third of patients with major depressive disorder experience treatment-resistant depression, contributing to higher morbidity and healthcare costs.
Electroconvulsive therapy is a key treatment for treatment-resistant depression but has limitations, including cognitive side effects and delayed symptom relief.
Repetitive transcranial magnetic stimulation may enhance the efficacy of electroconvulsive therapy based on previous trials.
The primary outcome measures the response rate after 10 ECT sessions, defined as a ≥ 50% reduction in Hamilton Depression Rating Scale scores.
Secondary outcomes include assessments of depression severity, cognitive function, and potential changes in brain structure and connectivity.
Simplified
BACKGROUND: Major depressive disorder is a leading cause of disability worldwide, with (TRD) affecting approximately one-third of patients and leading to increased morbidity and healthcare costs. (ECT) remains a key treatment for TRD, but its efficacy is limited, and it is associated with cognitive side effects and delayed symptom relief. (rTMS) shares action mechanisms with ECT and has shown potential in enhancing ECT efficacy in a previous trial. The STIMAGNECT 2 trial aims to evaluate whether an rTMS add-on protocol can improve ECT outcomes in TRD patients after 10 ECT sessions.
METHODS: Eighty patients with TRD will be enrolled in a prospective multicentric double-blind randomized controlled trial. All patients will receive a total of 10 ECT sessions. Patients will be randomly assigned to an active or sham rTMS arm. The rTMS protocol (either active or sham) consists of 5 rTMS sessions over 4 days before the beginning of the ECT protocol, with an additional rTMS session the day before each ECT session from the 6th ECT session onward. The main outcome is the response rate following 10 ECT sessions, defined as the proportion of patients achieving a ≥ 50% reduction in their Hamilton Depression Rating Scale (HAMD, 21 items). Secondary outcomes include changes in depression severity (HAMD and QIDS-SR-16) at baseline, during the protocol (Day 4, Day 19, Day 26) and at the end of the protocol, as well as assessment of side effects (adapted UKU), cognitive function (memory, attention, visuospatial abilities, subjective cognitive complaint), autobiographical memory (TEMPau), and ECT session parameters such as seizure characteristics and anesthetic doses. Additionally, potential changes in regional gray matter density, cortical thickness, brain connectivity, and GABA levels will be compared between groups using several magnetic resonance imaging (MRI) sequences (3D, resting-state functional MRI, magnetic resonance spectroscopy).
DISCUSSION: The aim of this trial is to optimize neurostimulation protocols using the synergistic effects of rTMS and ECT in order to improve the treatment of TRD.
TRIAL REGISTRATION: ClinicalTrials.gov NCT06391723 Id RCB: 2023-A01813-42. The trial was registered on January 30, 2024.
Key numbers
≥ 50%
Response Rate
Defined as the proportion of patients achieving a reduction in HAMD scores after 10 sessions.
80 patients
Patient Enrollment
Total number of patients to be enrolled in the trial.
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Declarations. Ethics approval and consent to participate {24}: This study will be conducted in accordance with legal and regulatory requirements, as well as the general principles set forth in the International Ethical Guidelines for Biomedical Research Involving Human Subjects (Council for International Organizations of Medical Sciences, 2002), Guidelines for Good Clinical Practice (International Conference on Harmonization, 1996), and the Declaration of Helsinki (World Medical Association 1996 and 2008). In addition, the study will be conducted in accordance with the protocol, the International Conference on Harmonization Guideline on Good Clinical Practice, and applicable local regulatory requirements and laws (law n°2004-806, August 9th 2004). This protocol obtained a favorable opinion of the Independent Ethics Committee (art. L1123-6 of French Public Health Code), and the National Agency for the Safety of Medicines and Health Products (ANSM) was informed. All participants in the study will sign an informed consent form. Agreement of their legal guardian for patients under guardianship will be asked. The promoter of this research, the Centre Hospitalier du Rouvray, 4 rue Paul Eluard, 76300 Sotteville-lès-Rouen, France, has purchased civil liability insurance from the Société Hospitalière d’Assurance Mutuelle. Consent for publication {32}: Not applicable. Competing interests {28}: The authors declare that they have no competing interests.
