Abstract
Objectives Treating a patient with schizophrenia experiencing auditory verbal hallucinations (AVH) with a usual low-frequency rTMS protocol is time consuming and seems to be poorly efficient according to the most recent meta-analyses. In this study, we tested a short treatment procedure with high-frequency stimulation and an accurate anatomical target guided by neuronavigation. Methods Seventy-four schizophrenic patients with AVHs were included in a double-blind multicenter randomized sham-controlled trial. The treatment procedure consisted in four sessions within two days. Each session included motor threshold assessment with an active coil whatever the arm. Then, the rTMS stimulation at 80% of the motor threshold (13 trains of 10 s at 20 Hz spaced by 50 s) was performed, using a neuronavigation device for the target localization and a placebo coil in the placebo arm. The target was determined beforehand on the individual MRI with an anatomical criteria based on a previous study. The AVHs were blindly assessed using the AHRS scale before (baseline) and after the treatment. Results The primary outcome was the percentage of responders, defined by a decrease of more than 30% of the total score on the Auditory Hallucinations Rating Scale after 2 weeks of treatment (D14). The percentage of responders was significantly higher in the active group (34.6%) than in the placebo group at D14 (34.6 vs. 9.1%, P = 0.016). Conclusion Our findings demonstrate in a large double blind trial that a two days rTMS treatment alleviated AVHs significantly more than the placebo. At least two points can explain this efficacy. First, the neuronavigated stimulation site was located more anteriorly and inferiorly than the classical T3P3 target. Second, the use of high-frequency stimulation over the temporal lobe may be inhibitory, as we demonstrated in healthy subjects in a previous EEG study.
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