Clinical, Cognitive and Neural Effects of Potentiation of ECT by rTMS in Treatment-Resistant Depression
- Conditions
- Major Depressive Disorder
- Interventions
- Device: Active rTMSDevice: Sham rTMS
- Registration Number
- NCT06391723
- Lead Sponsor
- Centre Hospitalier du Rouvray
- Brief Summary
Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD). However, due to response delay and cognitive impairment, ECT remains an imperfect treatment. In this multicenter, randomized, double-blind, sham-controlled study, our objective is to assess the priming effect of rTMS sessions before ECT on clinical, cognitive and neural response in patients with TRD.
- Detailed Description
80 patients with TRD will be assigned to active or sham rTMS before ECT treatment. Five sessions of active/sham rTMS will be administered over the left dorsolateral prefrontal cortex (20 Hz, 90% resting motor threshold, 20 2 s trains with 60-s intervals, 800 pulses/session) before ECT (which was active for all patients) started. Then, from the sixth ECT session, an rTMS session will occur the day before each ECT session. Clinical assessment, cognitive assessment and brain imaging (structural MRI, resting state functional MRI, MR spectroscopy) will take place before and after 10 ECT sessions. Clinical, cognitive and neural changes will be compared between both groups after 10 ECT sessions.
The primary outcome will be the response rate after 10 ECT, i.e. the percentage of patients who achieved a reduction of 50% or more from their initial Hamilton Depression Scale score (HAMD-21 items).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 80
- Patients with Major Depressive Disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria
- HAMD score ≥15
- In case of unipolar disorder: no remission after at least two different antidepressants prescribed at a dose and duration sufficient for the current episode
- In the case of bipolar disorder: no remission despite lithium at an adequate plasma level combined with lamotrigine or quetiapine monotherapy at full dose
- No change of antidepressant or mood stabilizer treatment for at least 15 days
- To be rTMS-naive
- Without benzodiazepine or antiepileptic treatment for at least 15 days
- To understand spoken and written French
- Having given their informed, written consent
- Contraindication to Electroconvulsive therapy (ECT), repeated Transcranial Magnetic Stimulation (rTMS), Magnetic Resonance Imaging (MRI), anesthesia
- Patients who have received ECT in the last 6 months
- Patients suffering from poorly stabilized epilepsy, serious neurological or systemic disorders
- Patients with a serious substance use disorder (other than nicotine or caffeine) according to DSM-5 criteria
- Patients suffering from severe hearing problems
- Subjects already treated with an electrical or magnetic stimulation technique
- Women who do not have adequate contraception, pregnant or breastfeeding women
- Being deprived of liberty by an administrative or judicial decision
- Patients participating or having participated in an interventional clinical trial within 30 days before the inclusion visit
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Active rTMS group Active rTMS 5 active rTMS before starting ECT, then from the sixth ECT session, an active rTMS session will occur the day before each ECT session Sham rTMS group Sham rTMS 5 sham rTMS before starting ECT, then from the sixth ECT session, a sham rTMS session will occur the day before each ECT session
- Primary Outcome Measures
Name Time Method Response rate after 10 ECT Day 0 and Day 40 the percentage of patients who achieved a reduction of 50% or more from their initial Hamilton Depression Scale score (HAMD-21 items)
- Secondary Outcome Measures
Name Time Method The relative improvement of depressive symptoms throughout the study (self-reported) Day 0, Day 4, Day 19, Day 26, Day 40 Quick Inventory of Depressive Symptomatology
Brain activity and biochemical changes Day 0 and Day 40 Changes measured with Resting state functional MRI and spectroscopy MRI
Attention (objective) Day 0 and Day 40 Scores and variations assessed the D2 test of attention
Autobiographical memory (objective) Day 0 and Day 40 Scores and variations assessed with the autobiographical memory test (TEMPau)
Dose of medication Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37 Dose of medication during ECT
Global cognitive functioning (objective) Day 0 and Day 40 Scores and variations assessed with the Mini Mental Status Examination
Seizure threshold Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37 Seizure threshold during ECT
Changes in regional gray matter density Day 0 and Day 40 Changes in regional gray matter density measured with 3D MRI
Changes in cortical thickness Day 0 and Day 40 Changes in cortical thickness measured with 3D MRI
The relative improvement of depressive symptoms throughout the study (assessed by a clinician) Day 0, Day 4, Day 19, Day 26, Day 40 the relative variation of HAMD-21
Adverse effects Day 4, Day 19, Day 26, Day 40 Assessment of adverse effects with the Udvalg for Kliniske Undersogelser (UKU) side effects rating scale adapted to rTMS (adapted UKU)
Subjective assessment of cognitive functioning Day 4, Day 19, Day 26, Day 40 Scores and variations in cognitive functioning assessed with the Cognitive Failures Questionnaire (CFQ)
Verbal memory performances (objective) Day 0 and Day 40 Scores and variations assessed with the RL/RI-16 test
Postictal Suppression Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37 Postictal Suppression during ECT
Subjective assessment of memory Day 4, Day 19, Day 26, Day 40 Scores and variations in memory assessed with the Squire Subjective Memory Questionnaire (SSMQ)
Visuospatial and constructional ability (objective) Day 0 and Day 40 Scores and variations assessed with the Rey-Osterrieth complex figure test
Seizure duration Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37 Seizure duration during ECT