Through imaging studies, a significant increase in cerebral activity has been detected in fronto-temporal areas in patients experiencing auditory verbal hallucinations. Therefore, non-invasive neuromodulation, in particular transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS), has been considered as a therapeutic intervention for medication-resistant auditory verbal hallucinations in schizophrenia. We aimed to synthesize results from randomized trials on either rTMS or tDCS versus placebo in patients with schizophrenia by including five recently published trials in the field. A systematic review and meta-analysis of relevant literature was conducted. Studies were included on the basis of pre-defined selection criteria. The quality of the studies was assessed by the Cochrane Risk of Bias Tool for Randomized Controlled Trials. RevMan 5.3 was used to conduct the statistical analysis. Including 465 and 960 patients, respectively, 12 tDCS and 27 rTMS studies were included. Regarding treatment of medication refractory auditory verbal hallucinations, no significant effect of tDCS (− 0.23 [-0.49, 0.02], p = 0.08) or rTMS (− 0.19 [-0.50, 0,11], p = 0.21) was found compared to sham in this meta-analysis. The current study found that it cannot be concluded that rTMS and tDCS are efficacious in treating medication-resistant auditory verbal hallucinations. Larger randomized controlled tDCS trials of a higher quality should be conducted in the future to establish substantial evidence of tDCS. The interventions appear safe and may have beneficial effects on other outcomes.
The majority of tDCS and rTMS studies on auditory verbal halluci- nations used a standard coil position, the international 10/20 EEG electrode system (Herwig et al., 2003). Criticism has been raised regarding the standard anatomic positioning of electrodes, as neuroimaging studies have shown that cortical activity during auditory hallucinations vary between subjects. The area of pathophysiology is not necessarily included in the area below the standard coil positioning (Bentaleb et al., 2002; Lennox et al., 2000; Shergill et al., 2000). Therefore, it would be favorable to locate individual physiological pathology through neuroimaging, followed by stereotactic neuronavigation to improve the treatment. Neuronavigation has never been applied in tDCS RCT’s and could possibly improve tDCS as a treatment modality. Moreover, the technique showed promising results and should be further investigated in rTMS.