Major Depressive Disorder
Conditions
Keywords
Treatment-resistant-depression, repetitive transcranial magnetic stimulation (rTMS), electroconvulsive therapy (ECT), combination of neurostimulation techniques
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).
Interventions
DEVICEActive rTMS
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)
DEVICESham rTMS
Sham rTMS will be administered over the left dorsolateral prefrontal cortex
Sponsors
University Hospital, Rouen
Centre Hospitalier Sainte Anne, Paris
Centre Hospitalier du Rouvray
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
Multicenter, randomized, double-blind, sham-controlled trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 memory | Day 4, Day 19, Day 26, Day 40 | Scores and variations in memory assessed with the Squire Subjective Memory Questionnaire (SSMQ) |
| 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) |
| Global cognitive functioning (objective) | Day 0 and Day 40 | Scores and variations assessed with the Mini Mental Status Examination |
| Verbal memory performances (objective) | Day 0 and Day 40 | Scores and variations assessed with the RL/RI-16 test |
| Attention (objective) | Day 0 and Day 40 | Scores and variations assessed the D2 test of attention |
| Visuospatial and constructional ability (objective) | Day 0 and Day 40 | Scores and variations assessed with the Rey-Osterrieth complex figure test |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Brain activity and biochemical changes | Day 0 and Day 40 | Changes measured with Resting state functional MRI and spectroscopy MRI |
| Autobiographical memory (objective) | Day 0 and Day 40 | Scores and variations assessed with the autobiographical memory test (TEMPau) |
Contacts
Primary ContactMaud Rotharmel
Backup ContactVirginie Moulier
Outcome results
None listed