Clinical, Cognitive and Neural Effects of Potentiation of ECT by rTMS in Treatment-Resistant Depression

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).

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