Negative symptoms in schizophrenia impose a significant burden with limited effective pharmacological treatment options. Recent trials have shown preliminary evidence for the efficacy of using intermittent theta burst stimulation (iTBS) in treating negative symptoms in schizophrenia. We aim to systematically review the current evidence of iTBS in the treatment of the negative symptoms of schizophrenia as an augmentation therapy. The study protocol was developed and registered on Prospero (registration ID: 323381). MEDLINE, EMBASE, Web of Science (Scopus), PsycINFO and Wan Fang databases were searched for sham-controlled, randomized trials of iTBS among patients with schizophrenia. The mean difference in major outcome assessments for negative symptoms was calculated. The quality of evidence was assessed using the Cochrane Risk of Bias Tool (version 1) and the GRADE system. Moreover, 12 studies including a total of 637 participants were included. Compared to sham treatment, the pooled analysis was in favor of iTBS treatment for negative symptoms (mean weight effect size: 0.59, p = 0.03) but not for positive symptoms (mean weight effect size: 0.01, p = 0.91) and depressive symptoms (mean weight effect size: 0.35, p = 0.16). A significant treatment effect was also observed on the iTBS target site left dorsal prefrontal cortex (mean weight effect size: 0.86, p = 0.007) and for stimulation with 80% motor threshold (mean weight effect size: 0.86, p = 0.02). Thus, our synthesized data support iTBS as a potential treatment for negative symptoms among patients with schizophrenia. However, the long-term efficacy and safety issues of iTBS in a larger population have yet to be examined.
Keywords: iTBS; negative symptoms; schizophrenia; side effect; treatment parameters.