How increasing the effect of rTMS in the treatment of auditory hallucinations in schizophrenia

Repetitive transcranial magnetic stimulation (rTMS) shows a high inter-subjects variability in the efficacy of treatment of auditory verbal hallucinations (AVH) in schizophrenia. The aim of this presentation is to demonstrate the involvement of several factors in the efficacy of rTMS such as the frequency of stimulation, the placebo effect and the brain morphology underlying the target of stimulation. Methods A meta-analysis was conducted to determine the effect sizes of placebo effect in 21 controlled studies on rTMS in the treatment of AVH in schizophrenia. MRI was also acquired in patients treated by rTMS to evaluate the scalp to cortex distances (SDCs) and the gray matter densities (GMDs) at the target of stimulation. Finally, we evaluated the efficacy of high (20 Hz) frequency stimulation in a controlled placebo study. Results Weak or no placebo effect in the control groups led to reveal a superiority of active rTMS over sham rTMS in the treatment of AVH. Clinical efficacy of rTMS was also correlated with the SCD or the GMD at the region of the target stimulation. Finally, we also demonstrated that more responders were observed after 2 weeks in the active group treated by 20 Hz than in the placebo group. Conclusion We clearly demonstrated that several factors such as high frequency, the placebo effect, anatomical cortical variations can impact on the efficacy of rTMS. These results fundamentally inform the design and the method of further controlled studies, particularly with respect to studies of rTMS in the treatment of AVH.