The Therapeutic Role of Intermittent Theta Burst Stimulation in Schizophrenia: A Systematic Review and Meta-analysis.

ABSTRACT:Schizophrenia affects approximately 1% of the population worldwide. Multifactorial reasons, ranging from drug resistance to adverse effects of medications, have necessitated exploring further therapeutic options. Intermittent theta burst stimulation (iTBS) is a novel high-frequency form of transcranial magnetic stimulation, a safe procedure with minor adverse effects with faster and longer-lasting poststimulation effects with a potential role in treating symptoms; however, the exact target brain regions and symptoms are still controversial. Therefore, we aimed to systematically investigate the current literature regarding the therapeutic utilities of iTBS using Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Twelve studies were included among which 9 found iTBS effective to some degree. These studies targeted the dorsolateral prefrontal cortex and the midline cerebellum. We performed a random-effects meta-analysis on studies that compared the effects of iTBS on schizophrenia symptoms measured by the Positive and Negative Syndrome Scale (PANSS) to sham treatment. Our results showed no significant difference between iTBS and sham in PANSS positive and negative scores, but a trend-level difference in PANSS general scores (k = 6, P = 0.07), and a significant difference in PANSS total scores (k = 6, P = 0.03). Analysis of the studies targeting the dorsolateral prefrontal cortex showed improvement in PANSS negative scores (k = 5, standardized mean difference = -0.83, P = 0.049), but not in PANSS positive scores. Moderators (intensity, pulse, quality, sessions) did not affect the results. However, considering the small number of studies included in this meta-analysis, future works are required to further explore the effects of these factors and also find optimum target regions for positive symptoms.