Repetitive Transcranial Magnetic Stimulation (rTMS) is a non invasive technique which was shown to be effective in the treatment of major depression.

The dorsolateral prefrontal cortex (DLPFC) is the anatomic target in rTMS studies and the standard (manual) '5-cm method' for positioning the coil over DLPFC is the reference. Nevertheless, it has been criticized due to poor targeting accuracies attributed to inter-subject variability.

Such an inaccuracy could have any therapeutic consequences as a decrease in rTMS efficacy.

Preliminary findings suggest that a more reproductible and accurate method, based upon a neuronavigation system could allow for a better efficacy. This finding has to be replicated with sound methodology.

Investigator's objective is to compare efficacy on mood of coil positioning based upon a neuronavigation device versus coil positioning based upon the standard method.

Background :

Repetitive Transcranial Magnetic Stimulation (rTMS) is a new tool for major depressive disorder.

rTMS is a non invasive technique allowing for a localized stimulation of cerebral tissue cortex. rTMS uses electromagnetic induction to induce weak electric currents using a rapidly changing magnetic field; this can modify activity in specific or general parts of the brain.

Meta-analyses have stated that rTMS appeared to be effective in the treatment of major depression despite any limits concerning sample sizes and methodological concerns.

Studies have shown that this technique potentiates antidepressants treatment in combination therapy.

It has received FDA approval for the management of major depressive disorder. Stimulation parameters are numerous (frequency, intensity, number of pulses) and their effects are increasingly better understood in order to predict a better balance between efficacy and tolerability.

The dorsolateral prefrontal cortex (DLPFC) is the target in repetitive transcranial magnetic stimulation and the standard (manual) '5-cm method' for positioning the transcranial magnetic stimulation coil over DLPFC is the reference. It has been criticized due to poor targeting accuracies attributed to inter-subject variability.

Such an inaccuracy could have consequences as a decrease in rTMS efficacy. Any preliminary findings suggest that a more reproductible and accurate method, based upon a neuronavigation system could allow for a better efficacy. This finding has to be replicated with sound methodology.

Objectives:

To compare efficacy on mood of coil positioning based upon a neuronavigation device versus coil positioning based upon the standard method.

Investigators hypothesized that an accurate localization and stimulation of DLPFC using neuronavigation would be more effective than the less accurate standard method.

A secondary objective is to compare the efficacy on patient's self perception, on psychomotor symptoms and the tolerability of the two methods.

Inclusion Criteria:

• Patients giving their consent;
• Right handed;
• Age > 18 and < 65;
• With a DSM-IV diagnosis of MDD, single episode or recurrent;
• With an antidepressant treatment unchanged in the 3 last weeks;
• With an MADRS score ≥ 21;
• Benzodiazepine treatments have to be avoided;

Exclusion Criteria:

• Major depressive episode with psychotic characteristics;
• A lifetime of the following axis 1 diagnoses: schizophrenia or substance use disorder (alcohol or other substance);
• Stade 5 of Thase and Rush classification ;
• Involuntary hospitalizations;
• Patients under guardianship;
• Outpatients in case of an increased risk of suicide as assessed by a MADRS item 10 > 3;
• Contraindication for MRI or rTMS: a personal history of a seizure disorder, presence of neurologic or neurosurgical disorder, presence of ferromagnetic material (including intraocular) or metallic medical devices (pacemakers);
• Pregnancy.