The MULTIMODHAL randomized controlled trial: fMRI-based symptom capture for guiding rTMS treatment of drug-resistant hallucinations in patients with schizophrenia.
Jardri, R.; Yger, P.; Amor, Z.; Plaze, M.; Amad, A.; Roman, D.; Szaffarczyk, S.; Lefebvre, S.; Pins, D.; Cuenca, M.; Coudriet, G.; Cachia, A.; Labreuche, J.; Cailliau, E.; Delmaire, C.; Outteryck, O.; Lopes, R.; Pruvo, J.-P.; Edjlali-Goujon, M.; Oppenheim, C.; Bubrovszky, M.; Vaiva, G.; Thomas, P.; The MULTIMODHAL Study Group, ; Domenech, P.; Leroy, A.
Show abstract
Auditory-verbal hallucinations (AVHs) are among the most disabling symptoms of schizophrenia and often persist despite the use of adequate antipsychotic treatment. Conventional low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the T3P3 scalp site has demonstrated limited efficacy, likely due to interindividual variability in AVH-related brain networks. In this multicenter, randomized, double-blind phase 3 trial, 70 patients with drug-resistant AVHs received active 1-Hz rTMS targeted either with an individualized fMRI-based symptom-capture procedure or by using conventional T3P3 localization. fMRI-guided rTMS yielded a greater reduction in Auditory Hallucination Rating Scale (AHRS) scores at one month (mean difference, -5.43; 95% CI, -8.92 to -1.94), and the effects were sustained at three and six months. The number-needed-to-treat for neuroguided rTMS was 3.5. Clinical response was associated with greater E-field overlap with AVH-related networks. These findings demonstrate that fMRI-guided neuronavigation increases rTMS efficacy, thus supporting its use to optimize the treatment of drug-resistant AVHs in schizophrenia.
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