Treatment of Major Depression by rTMS on Dorsolateral Prefrontal Cortex: Study of Underlying Mechanisms (DEPSTIM)

Centre Hospitalier Universitaire de Besancon

Status

Enrolling

Conditions

Depressive Disorder, Major

Treatments

Device: iTBS

Study type

Interventional

Funder types

Other

Identifiers

NCT05121129

2020/477

Details and patient eligibility

About

The study aims to evaluate the impact of repeated Transcranial Magnetic Stimulation (rTMS) on underlying neuronal mechanisms of adults suffering from major depression disorder (MDD). Short- and long-term effects are assessed by High-Resolution electroencephalography (HR-EEG) or Magnetic Resonance Imaging (MRI) records, experimental tasks and self-rated scales.

Full description

Depression is associated with functional and structural changes in the brain, notably in DLPFC (DorsoLateral PreFrontal Cortex). High-frequency rTMS (10 Hz) applied to the left DLPFC is associated with a response rate 3.75 times and remission 2.52 higher than placebo for the treatment of MDD with more reproducible results than those observed for the others rTMS stimulation modalities (low frequency, iTBS5). rTMS is validated as an indication for the treatment of MDD by all learned societies and regulatory authorities in a large number of countries, except in France. Limiting factors concern the lack of knowledge of the action mechanisms, due in particular to the absence of studies based on animal models, the focused application of TMS in rodents being a challenge that few teams have mastered. The rationale for the therapeutic use in the treatment of MDD is now based on some functional brain imaging data showing that rTMS induces a lasting change in brain activity at the site of stimulation (CPFDL) but also in remote interconnected areas such as the limbic region or the amygdala. The DEPSTIM clinical project is part of a translational project with a fundamental approach in rodents.

The main objective is to demonstrate that remission following rTMS of CPFDL occurs via the activation of CPFDL projections to these dysfunctional subcortical areas in MDD.

With a prospective, open design, this study aims to evaluate the impact of iTBS over the left DLPFC on neuronal mechanisms of adults suffering from MDD. Subjects will be submitted to 25 intermittent TBS (iTBS) stimulation sessions for five consecutive days (5 sessions of 9.5 minutes/day, 1,800 pulses per session, 90% of resting motor threshold, placed over the left DLPFC, as mentionned by Cole et al, 2018 (Stanford Neuromodulation Therapy: SNT)). Baseline measures will be compared to those obtained immediately after the end of sessions (Day 5 (D5): short-term effects with HR-EEG analysis), and 30 days (D30) later (long-term effects with MRI analysis).

Enrollment

30 estimated patients

Sex

All

Ages

35 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Diagnosis of MDD (Diagnostic and Statistical Manual of Mental Disorders V [DSM-V] and (Mini International Neuropsychiatric Interview [MINI] criteria, QIDS-C16≥18)
Right-handed
No response at a first antidepressant
Under AD ≥ 6 weeks
No contraindications for rTMS and MRI
Absence of addictive comorbidities
Absence of severe progressive neurologic and/or somatic pathologies (specially tumors, neurodegenerative diseases)
Inpatients or outpatients of Adult Psychiatric Department
Signed informed consent form
Subjects affiliated to or beneficiary from a French social security regime

Exclusion criteria

Subjects under 35 years old or over 65 years old
Treated with over 4 AD for the current episode
ECT or rTMS for current episode
BZD or antiepileptic (except pregabalin up to 75 mg / d, zopiclone ≤7.5 mg / d)
Left-handed
Subject under measure of protection or guardianship of justice
Presence of psychiatric comorbidities
Subject beneficiary from a legal protection regime
Subject unlikely to cooperate or low cooperation stated by investigator
Subject not covered by social security
Pregnant woman
Subject being in the exclusion period of another study or provided for by the "National Volunteer File