The primary objective of the study is to determine the predictive value of the neuroendocrine tests TRH-∆∆TSH (thyreoliberin - thyreostimulin) and DST (dexamethasone suppression test) in the subsequent response to rTMS-TBS (repetitive transcranial magnetic stimulation-theta burst stimulation) treatment, defined as at least a 50% decrease in depression score after 20 sessions of rTMS-TBS.

Conduct of research :

This is a monocentric, non-randomized, open-label pilot study involving 50 male and female patients aged 18 to 65, hospitalized for major depression and presenting with an indication for treatment with repeated theta-burst transcranial magnetic stimulation (rTMS-TBS), i.e. a situation of therapeutic failure following 2 well-conducted antidepressant treatments.

At the end of the 20 rTMS-TBS sessions (one session per day, except weekends), the clinical response will be assessed by an investigator "blind" to the endocrine results. This response will be analyzed according to the status of neuroendocrine tests at inclusion (TRH-∆∆TSH and DST) and at the end of the study (for those who had one or more abnormal tests at inclusion and in whom the same tests were repeated at the end of the rTMS-TBS sessions).

During the inclusion visit, the patient and investigator sign the consent form, after double-checking the inclusion and non-inclusion criteria.

Immediately after the tenth rTMS session, an assessment of depression using the HAMD (17-item Hamilton Depression Scale) scale will be carried out by an independent psychiatrist, blind to the results of the neuroendocrine tests. This psychiatrist, who has already administered the HAMD at V0, will repeat the assessments at V1 and V2.

Immediately after the twentieth rTMS session, an assessment of depression using the HAMD scale will be carried out by an independent psychiatrist. This assessment will determine responder/non-responder status to rTMS-TBS.

Inclusion Criteria:

1. Patient with a characterized depressive episode defined according to DSM-5 (diagnostic and statistical manual of mental disorders) criteria;
2. Patient between the ages of 18 and 65 years;
3. Inpatient with an inadequate response to two prior well-conducted antidepressant treatments (Hamilton 17-item scale [HAMD-17] score at inclusion≥ 18) ;
4. Patient with written informed consent to participate in the study;
5. Patient enrolled in or receiving social security benefits.

Exclusion Criteria:

1. Patient with endocrinopathy ;

2. Patient with a contraindication to neuroendocrine testing (hypersensitivity to the active substance or to one of the excipients);

3. Patient with a contraindication to rTMS:

   • cochlear implant,
   • cardiac pacemaker,
   • metal clips, stents or other electronic implants within one meter of the stimulation coil,
   • intracranial hypertension,
   • poorly balanced comitiality,
   • in the case of well-balanced comitiality, a neurological consultation with electroencephalogram (EEG) is planned before including the patient;

4. Patient previously treated with monoamine oxidase inhibitor (MAOI) antidepressant or lithium salts (within 6 months prior to inclusion);

5. Pregnant or lactating patient;

6. Patient under court protection or deprived of liberty;

7. Patient under guardianship/guardianship.