High-Frequency Neuronavigated rTMS in Auditory Verbal Hallucinations: A Pilot Double-Blind Controlled Study in Patients With Schizophrenia

Sonia Dollfus (1, 2, 3) , Nemat Jaafari (4, 5) , Olivier Guillin (6, 7, 8) , Benoit Trojak (9) , Marion Plaze (10) , Ghassen Saba (11) , Cecilia Nauczyciel (12) , Aurélie Montagne Larmurier (1, 2) , Nathalie Chastan (13, 14) , Vincent Meille (9) , Marie-Odile Krebs (10) , Samar Ayache (15) , Jean Pascal Lefaucheur (16) , Annick Razafimandimby (3) , Elise Leroux (17) , Rémy Morello (18) , Jean Marie Batail (12) , Perrine Brazo (3, 1, 2) , Nicolas Lafay (5) , Issa Wassouf (5) , Ghina Harika-Germaneau (19) , Rémy Guillevin (19) , Carole Guillevin (20) , Emmanuel Gérardin (21, 7) , Maud Rotharmel (8) , Benoît Crépon (10) , Raphaël Gaillard (10) , Christophe Delmas (8) , Gael Fouldrin (7) , Guillaume Marc Laurent (8) , Clément Nathou (1, 2, 3, 8) , Olivier M Etard (22)

1 Service de psychiatrie [CHU Caen]
2 Centre Esquirol [CHU Caen]
3 ISTS - Imagerie et Stratégies Thérapeutiques de la Schizophrénie
4 CIC 1402 - CIC Poitiers – Centre d'investigation clinique de Poitiers
5 CHL - Centre Hospitalier Henri Laborit
6 Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques
7 Hôpital Charles Nicolle [Rouen]
8 Centre Hospitalier du Rouvray
9 Service de psychiatrie générale et addictologie [CHU de Dijon]
10 Centre Hospitalier Sainte Anne [Paris]
11 Pôle de Psychiatrie [Hôpital Henri Mondor]
12 Centre Hospitalier Guillaume Régnier [Rennes]
13 Service de neurophysiologie [Rouen]
14 COMETE - Mobilités : Vieillissement, Pathologie, Santé
15 CHU Henri Mondor - Département de physiologie
16 ENT - Excitabilité nerveuse et thérapeutique
17 ISTS - Imagerie et Stratégies Thérapeutiques de la Schizophrénie
18 UBRC - Unité de Biostatistique et de Recherche Clinique
19 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
20 LMA [Poitiers] - Laboratoire de mathématiques et applications [UMR 7348]
21 Service d'Imagerie Médicale [CHU Rouen]
22 Service des Explorations Fonctionnelles [CHU Caen]

Introduction: Despite extensive testing, the efficacy of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) of temporo-parietal targets for the treatment of auditory verbal hallucinations (AVH) in patients with schizophrenia is still controversial, but promising results have been reported with both high-frequency and neuronavigated rTMS. Here, we report a double-blind sham-controlled study to assess the efficacy of high-frequency (20 Hz) rTMS applied over a precise anatomical site in the left temporal region using neuronavigation. Methods: Fifty-nine of 74 randomized patients with schizophrenia or schizoaffective disorders (DSM-IV R) were treated with rTMS or sham treatment and fully evaluated over 4 weeks. The rTMS target was determined by morphological MRI at the crossing between the projection of the ascending branch of the left lateral sulcus and the superior temporal sulcus (STS). Results: The primary outcome was response to treatment, defined as a 30% decrease of the Auditory Hallucinations Rating Scale (AHRS) frequency item, observed at 2 successive evaluations. While there was no difference in primary outcome between the treatment groups, the percentages of patients showing a decrease of more than 30% of AHRS score (secondary outcome) did differ between the active (34.6%) and sham groups (9.1%) (P = .016) at day 14. Discussion: This controlled study reports negative results on the primary outcome but demonstrates a transient effect of 20 Hz rTMS guided by neuronavigation and targeted on an accurate anatomical site for the treatment of AVHs in schizophrenia patients.

Mots clés: magnetic resonance imaging; Auditory Hallucinations Rating Scale; placebo; trial; 20 Hz; Transcranial magnetic stimulation; neuronavigation

Domaines: Sciences du Vivant [q-bio]; Neurosciences; Psychologie

Sonia Dollfus, Nemat Jaafari, Olivier Guillin, Benoit Trojak, Marion Plaze, et al.. High-Frequency Neuronavigated rTMS in Auditory Verbal Hallucinations: A Pilot Double-Blind Controlled Study in Patients With Schizophrenia. Schizophrenia Bulletin, 2018, 44 (3), pp.505-514. ⟨10.1093/schbul/sbx127⟩. ⟨hal-02190488⟩