Efficacy and safety of non-invasive brain stimulation on cognitive function for cognitive impairment associated with schizophrenia: A systematic review and meta-analysis

Based on existing evidence of the effects of the most commonly used non-invasive brain stimulation (NIBS), which includes transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), we conducted a meta-analysis to investigate the cognitive improvement and safety of NIBS on schizophrenia-related cognitive impairment. PubMed, EMBASE, Cochrane Library, and Web of Science were searched. The Cochrane Risk of Bias tool was used to assess the risk of bias of the included RCTs; Review Manager, version 5.4.1, was used to perform the statistical analysis. Twenty double-blind, randomized, sham-controlled trials involving 997 patients were included. As a result, no significant improvement in cognitive function was observed after NIBS treatment. However, the overall treatment effect of the two main NIBS modes (i.e., rTMS and tDCS) was associated with significantly larger improvements in negative symptoms and good tolerability in patients with schizophrenia compared to sham-controls (SMD = -0.56, 95% CI [-1.03, -0.08], p = 0.02, I-2 = 88%). NIBS model and stimulus parameters influenced the effect of NIBS. More favorable effects were observed in patients who received rTMS stimulation (SMD = 0.25, 95% CI [0.01, 0.49], p = 0.04, I-2 = 0%) in the left dorsolateral prefrontal cortex with a stimulation intensity of 20 Hz (p = 0.004) for a period longer than 1 month (p < 0.05). Yet, due to the limited number of included studies and heterogeneity in both study design and target population, the results of this analysis need to be interpreted with caution.