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

Official title

Clinical, Cognitive and Neural Effect of Potentiation of Electroconvulsive Therapy (ECT) by Repetitive Transcranial Magnetic Stimulation (rTMS) at 10 ECT in Patients With Characterized Pharmacoresistant Depressive Episode

Overview

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

• Device Active 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)
• Device Sham rTMS
  Sham rTMS will be administered over the left dorsolateral prefrontal cortex

Primary outcome measures

• Response rate after 10 ECT [Time frame: Day 0 and Day 40]

Secondary outcome measures (12)

• The relative improvement of depressive symptoms throughout the study (assessed by a clinician) [Time frame: Day 0, Day 4, Day 19, Day 26, Day 40]
• The relative improvement of depressive symptoms throughout the study (self-reported) [Time frame: Day 0, Day 4, Day 19, Day 26, Day 40]
• Adverse effects [Time frame: Day 4, Day 19, Day 26, Day 40]
• Subjective assessment of memory [Time frame: Day 4, Day 19, Day 26, Day 40]
• Subjective assessment of cognitive functioning [Time frame: Day 4, Day 19, Day 26, Day 40]
• Global cognitive functioning (objective) [Time frame: Day 0 and Day 40]
• Verbal memory performances (objective) [Time frame: Day 0 and Day 40]
• Attention (objective) [Time frame: Day 0 and Day 40]
• Visuospatial and constructional ability (objective) [Time frame: Day 0 and Day 40]
• Autobiographical memory (objective) [Time frame: Day 0 and Day 40]
• Seizure threshold [Time frame: Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37]
• Seizure duration [Time frame: Day 5, Day 9, Day 11, Day 16, Day 18, Day 23, Day 25, Day 30, Day 32, Day 37]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Clabeau L, Moulier V, Kaczmarek B, Dalmont M, Batail JM, Bouaziz N, Brunelin J, Calvet B, Daudet C, Dollfus S, Domenech P, Drapier D, Galvao F, Gohier B, Harika-Germaneau G, Holtzmann J, Jaafari N, Jalenques I, Januel D, Kazour F, Laurin A, Letourneur F, Pouchon A, Samalin L, Sauvaget A, Szekely D, Vinckier F, Le Clezio C, Compere V, Gerardin E, Guillin O, Quesada P, Rotharmel M. A prospective mul PMID 41582128

Identifiers

NCT: NCT06391723 · 2023-A01813-42

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗