Efficacy of non-invasive brain stimulation on the symptom dimensions of schizophrenia: A meta-analysis of randomized controlled trials

Abstract Background Transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have shown promise in the treatment of schizophrenia. Objective To quantify the efficacy of double-blind randomized controlled trials (RCT) of tDCS and rTMS for the positive and negative symptoms of schizophrenia and identify significant moderators relating to patient-related features and stimulation parameters. Methods Systemic review and meta-analyses of the relevant literature published until February 1st, 2017 to assess treatment efficacy and quantify the contribution of potential moderator variables. Results We identified 7 RCTs on tDCS (involving 105 participants) and 30 RCTs on rTMS (involving 768 participants). Compared to sham, tDCS improved all symptom dimensions but the effect reached significance for negative symptoms (Hedge’s g = −0.63, p = 0.02). Efficacy for positive but not negative symptoms was linearly associated with cumulative tDCS stimulation. Compared to sham, rTMS improved hallucinations (Hedge’s g = −0.51, p < 0.001) and negative symptoms (Hedge’s g = −0.49, p = 0.01) but was associated with modest, non-significant worsening of positive symptoms (Hedge’s g = 0.28, p = 0.13). Higher pulse frequency (>10 Hz), motor threshold intensity of 110%, left prefrontal cortical treatment site and trial duration over 3 weeks were associated with improvement in negative symptoms and worsening in positive symptoms (all p < 0.03). Conclusions The symptom dimensions in schizophrenia may respond differently to brain stimulation interventions in a way that may reflect the interaction between disease- and treatment-related mechanisms. Our findings underscore the need for further research into patient selection prior to treatment assignment and greater refinement of stimulation protocols.