Efficacy Towards Negative Symptoms and Safety of Repetitive Transcranial Magnetic Stimulation Treatment for Patients with Schizophrenia: A Systematic Review.

Background: Negative symptoms are one of the most difficult areas in the treatment of schizophrenia because antipsychotics are often less effective towards them. Repetitive transcranial magnetic stimulation (rTMS) is a new technique for cerebral cortex stimulation and is believed to be a safe and promising method for the treatment of mental disorders. As the clinical research and new treatment models have increased in recent years, the efficacy towards negative symptoms and safety evaluation of rTMS treatment should also be updated.

Aims: To explore the efficacy and safety of rTMS in the treatment of negative symptoms for patients with schizophrenia.

Methods: We searched for relevant controlled clinical trials from the following databases: PubMed, EMBASE, the Cochrane Library, EBSCO, Web of Science, China National Knowledge Infrastructure (CNKI), VIP, Wanfang Data, SINOMED, and Airiti Library. The retrieval time went up to January 2, 2017. The research literature was screened according to the predefined inclusion and exclusion criteria. After data extraction, statistical analysis was conducted by using RevMan 5.3 and Stata 14. Quality evaluation was done on the included research articles. The Cochrane risk of bias assessment tool was adopted for assessing risk of bias. The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system recommendation grading method was used as the reference standard.

Results: A total of 3500 articles were retrieved. In the end, there were 29 articles included in the metaanalysis with a total sample size of 1440. After the meta-analysis, it was found that the use of antipsychotic treatment combined with rTMS could improve the negative symptoms of patients (SMD=-0.40, 95% CI= -0.62~-0.18). Based on the bias of the efficacy evaluation assessed by the Cochrane risk of bias assessment tool, there were 6 studies rated as having "high risk of bias" and the rest were rated as "unable to determine". According to the assessment, development and evaluation criteria of the GRADE classification, the evidence quality for the efficacy evaluation index was "moderate". The acceptability of rTMS treatment was better (RR= 0.75, 95% CI= 0.49~1.15, based on the 1492 samples from the 28 studies), however, the patients who received the rTMS treatment had a higher rate of mild adverse effects (RR= 2.20, 95% CI= 1.53~ 3.18, based on the 1296 samples from the 23 studies).

Conclusions: The use of the antipsychotic treatment incorporated with rTMS treatment can slightly improve the negative symptoms of patients with schizophrenia and has better acceptability and fewer adverse effects. Nevertheless, there is publication bias in this study and the heterogeneity of the study is relatively high. Therefore, we need to be cautious when interpreting the results.