Efficacy and long-term effects of intermittent theta burst stimulation on negative symptoms in schizophrenia: a systematic review and meta-analysis

This study aims to investigate the clinical efficacy and long-term benefits of intermittent theta burst stimulation (iTBS) in alleviating negative symptoms in patients with schizophrenia. Two authors independently identified eligible studies from the Medical Literature Analysis and Retrieval System Online, Cochrane Library, Web of Science, and Excerpta Medica Database databases up to October 21, 2024. Our meta-analysis was conducted using Review Manager 5.3 and Stata 14 software. Seventeen randomized controlled trials with a total of 764 participants were included in the meta-analysis. iTBS demonstrated greater efficacy in alleviating negative symptoms immediately after treatment (standardized mean difference = -0.55, 95% confidence interval: -1.00 to -0.10). Improved outcomes were associated with stimulation targeting the left dorsolateral prefrontal cortex, delivery of more than 9900 pulses across over 10 sessions, and use of a stimulation intensity at 80% of the motor threshold. The follow-up results indicated that the iTBS group exhibited greater efficacy than the sham group only at the 6-month mark (standardized mean difference = -0.56, 95% confidence interval: -1.10 to -0.02). iTBS also reduced Positive and Negative Syndrome Scale general and total scores, whereas no significant effect was observed for positive symptoms. Our meta-analysis suggests that iTBS may alleviate negative symptoms in schizophrenia, with preliminary evidence of long-term benefits observed at the 6-month follow-up.