Efficacy of Maintenance Repetitive Transcranial Magnetic Stimulation (rTMS) in Auditory Verbal Hallucinations

To investigate the clinical efficacy of a 4-month maintenance procedure of rTMS in AVH reduction, a multicenter, controlled, double-blind study enrolling 120 patients randomly assigned in two groups is proposed. The active group will receive active rTMS with a two-day intense procedure (consisting in 4 20-Hz rTMS sessions within two days) and a maintenance phase with a two- rTMS session every week for one month and then every two weeks the next 3 months (i.e. 24 rTMS sessions). The individual target will be personalized and guided by neuronavigation. The placebo group will benefit from the exact same procedure but with sham rTMS instead of active rTMS. Patients will be carried out during 5 months and what distinguishes responders from non-responders will be studied. Among other variables, BDNF serum levels as a reflect of the individual neural plasticity and the measurement of the scalp-to-cortex distance to the target as a reflect of the cerebral morphological interindividual variations will be investigated.

Inclusion criteria

• Male or female; Age ≥ 18 years ≤ 65 years
• Diagnosis of schizophrenia or schizoaffective disorders according to DSM 5.0 criteria
• Patients treated with at least one antipsychotic medication
• Presence of auditory verbal hallucinations despite the optimization of the antipsychotic dosage for at least 6 weeks. This will be operationalized by a minimum AHRS score > 10
• Stable medication dosage for at least 6 weeks before the rTMS treatment
• Patient who understands the French language
• The agreement of the curatorship or tutorship in the case of a protected adult
• Willing to comply with scheduled visits, as outlined in the protocol
• Covered by, or having the right to Social Security or European cover
• Informed and written consent

Exclusion criteria

• Women who are pregnant
• Patients with contraindications for rTMS (history of epilepsy, neurologic stimulator, pacemaker, cardiac defibrillator, cardiac prosthesis, vascular prosthesis, intracranial clips or clamps, cerebrospinal fluid derivation, metallic splinters in the eyes)
• Patients included or planning to be included in another medical research protocol
• Patients unable to complete the protocol follow-up
• Any brain pathological abnormality known or diagnosed by the cerebral MRI
• Contre-indication for cerebral MRI (metallic fix tooth prosthesis, neurologic stimulator, pacemaker, cardiac defibrillator, cardiac prosthesis, vascular prosthesis, intracranial clips or clamps, cerebrospinal fluid derivation, metallic splinters in the eyes, severe claustrophobia)