Monocentric Pilot Study, for a Randomized, Crossover, Blinded Trial: Comparison of the Therapeutic Efficacy of Low Frequency Repeated Transcranial Magnetic Stimulation on Cortical Area 9 Compared to Brodmann Area 46 in the Treatment of Depressive Disorders.

Study Overview
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Brief Summary
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Repetitive transcranial magnetic stimulation (rTMS) is a new therapeutic tool used in psychiatry. Non-invasive, well tolerated and requiring no premedication, it is performed on an outpatient basis. The principle of this technique is to stimulate the cerebral cortex from an electromagnetic coil placed on the scalp. Unlike electroconvulsive therapy, rTMS induces an electrical current on a well-defined region of the cerebral cortex. In psychiatry, this technique is mainly considered in the treatment of depressive disorders resistant to antidepressant medication. The brain target, obtained from brain imaging data in depressed patients, is the dorsolateral prefrontal cortex (DLPFC). The Food and Drug Administration (FDA) has recognized the interest of rTMS for treating depressive disorders (October 7, 2008). However, some stimulation parameters still need to be optimized before rTMS can be considered a therapeutic method in its own right and used routinely. Indeed, its effectiveness over time has not yet been evaluated, and rTMS has shown a lack of reproducibility between subjects [Foucher, 2007]. Finally, the therapeutic results of rTMS are very modest whatever the study [Daskalakis, 2008]. Additional studies are therefore needed to optimize stimulation parameters.

Official Title
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Monocentric Pilot Study, for a Randomized, Crossover, Blinded Trial: Comparison of the Therapeutic Efficacy of Low Frequency Repeated Transcranial Magnetic Stimulation on Cortical Area 9 Compared to Brodmann Area 46 in the Treatment of Depressive Disorders.

Conditions
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Patients With Resistant Depressive Disorders

Intervention / Treatment
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* Device: rTMS BA9/BA46
* Device: rTMS BA46/BA9
* Radiation: brain MRI
* Other: Medical evaluation
* Other: Psychological assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with resistant depressive disorders (Hamilton-17-item scale > 22, failure ≥ 2 antidepressants) with at least one of the following criteria : venlafaxine treatment failure (unlike the national PHRC, patients who receive/have received venlafaxine treatment for the current depressive episode are included), therapeutic failure in PHRC national rTMS 2007, refusal to participate in the PHRC national rTMS 2007. Exclusion Criteria: Bipolar disorders: type I or II, Depression with psychotic characteristics, Schizophrenia, Risky or harmful use of alcohol and/or an illicit psychoactive substance, Dependence on alcohol and/or an illicit psychoactive substance, Sick and hospitalized under duress or under legal protection (guardianship, curatorship), Contraindication to the practice of rTMS; personal history of seizures, history of neurological or neurosurgical pathologies, metallic prosthetic materials or foreign bodies (pacemaker, etc...), Contraindication to brain MRI, Pregnancy or breastfeeding in progress Resistance to Escitalopram
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BA9/BA46<br> | Device: rTMS BA9/BA46<br>* 10 sessions of low-frequency repeated transcranial magnetic stimulation over two weeks on cortical area 9, then 4 weeks wash-out, then 10 sessions of low-frequency repeated transcranial magnetic stimulation repeated low frequency over two weeks on cortical area 46.<br>Radiation: brain MRI<br>* T1 weighted full-head high-resolution MRI with 1 mm seam cuts and sagittal orientation.<br>Other: Medical evaluation<br>* complete evaluation with 6 scales (HDRS, MADRS, Beck, CGI, COVI, UKU)<br>Other: Psychological assessment<br>* Subjective Life Profile Assessment (SLPA) and Helping Alliance Assessment<br>|
| Experimental: BA46/BA9<br> | Device: rTMS BA46/BA9<br>* 10 sessions of low-frequency repeated transcranial magnetic stimulation over two weeks on cortical area 46, then 4 weeks wash-out, then 10 sessions of low-frequency repeated transcranial magnetic stimulation repeated low frequency over two weeks on cortical area 9.<br>Radiation: brain MRI<br>* T1 weighted full-head high-resolution MRI with 1 mm seam cuts and sagittal orientation.<br>Other: Medical evaluation<br>* complete evaluation with 6 scales (HDRS, MADRS, Beck, CGI, COVI, UKU)<br>Other: Psychological assessment<br>* Subjective Life Profile Assessment (SLPA) and Helping Alliance Assessment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The remission rate | Compare the remission rates (decrease < 50% of the HDRS score / initial score) during neuronavigated stimulations on BA 9 and BA 46 compared to the average rate obtained during manual stimulation. | Through study completion, an average of 11 weeks. |