重复经颅磁刺激治疗对精神分裂症患者阴性症状的疗效和安全性:系统综述（英文）

Efficacy towards negative symptoms and safety of repetitive transcranial magnetic stimulation treatment for patients with schizophrenia:a systematic review

背景:阴性症状是精神分裂症治疗的难点之一,抗精神病药物对其疗效较差。重复经颅磁刺激(repetitive transcranial magnetic stimulation,r TMS)是一项新型脑皮质刺激技术,被认为是一项安全而有前景的精神障碍治疗方法,近年来临床研究及新的治疗模式增多,r TMS治疗阴性症状的疗效和安全性评价需要更新。目标:探索r TMS治疗对精神分裂症患者阴性症状的有效性及安全性。方法:我们从以下数据库搜索了相关的临床对照试验:Pub Med、EMBASE、the Cochrane Library、EBSCO、Web of science、中国知网、维普、万方、中国生物医学文摘数据库、台湾学术文献数据库等数据库,检索时间截止于2017年1月2日。按照预先定好的纳入和排除标准筛选研究文献,提取数据后应用Rev Man 5.3和Stata 14.0对数据进行统计分析。对纳入研究进行质量评价,采用Cochrane风险评估偏倚工具评估各种偏倚的风险性。结合GRADE(Grades of Recommendation,Assessment,Development,and Evaluation,GRADE)系统推荐分级方法为参照标准,进行主要结局指标证据水平的分级。结果:总共检索到3500篇文献,最终29篇文献纳入meta分析,合计样本量1440例。进行meta分析后发现,抗精神病药物治疗合并使用r TMS可改善患者的阴性症状(SMD=-0.40,95%CI=-0.62^-0.18)。根据Cochrane风险评估偏倚工具对疗效的评估的偏倚进行评估,其中6篇研究评价为"高偏倚风险",其它为"无法判断"。根据GRADE分级的评估、制定和评价标准,该疗效评估指标的证据质量是"中等"。r TMS治疗的可接受性较好(RR=0.75,95%CI=0.49~1.15,基于28项研究的1492例样本),但接受r TMS治疗的患者出现轻微不良反应的比率更高(RR=2.20,95%CI=1.53~3.18,基于23项研究的1296例样本)。结论:抗精神病药物治疗合并使用r TMS治疗可以一定程度改善精神分裂症患者的阴性症状,可接受性较好,不良反应较轻。但是本研究存在发表性偏倚,且研究的异质性较高,所以对结果进行解释时需要慎重。

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, 2027. 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 24. 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--0.28）. 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= 2.53- 3.18, based on the 2296 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