Su Liang, Lu Zheng, Shi Shenxun, Xu Yifeng
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Psychiatry, Huashan Hospital, Fudan University, School of Medicine, Shanghai, China.
Gen Psychiatr. 2018 Nov 10;31(2):e000016. doi: 10.1136/gpsych-2018-000016. eCollection 2018.
Agitation is very common in patients with acute stage schizophrenia, and injection of antipsychotics and clonazepam is widely used. Network meta-analysis of these comparisons among three injection treatments has been seldom reported.
To compare the efficacy and safety of various injections for agitation symptoms in Chinese patients with schizophrenia.
Searches were made in PubMed, Embase and Web of Knowledge, Cochrane Library, Wanfang data, CNKI, SinoMed and VIP databases up to 18 February 2018. Standard search strategies were performed by two reviewers according to the Cochrane Review Group. The Consolidated Standards of Reporting Trials statement was used to assess the methodological quality of the studies. STATA was used to perform meta-analysis. The Cochrane Grades of Recommendation, Assessment, Development and Evaluation (GRADE) was used to assess the strength of evidence.
A total of 15 studies were included in the network meta-analysis. There were 11 studies comparing ziprasidone with haloperidol, and four studies comparing haloperidol with clonazepam. The results showed that ziprasidone is more effective than haloperidol and clonazepam (sucra: 77.2, 72.8 and 0) in the treatment of agitation symptoms. There was the effect size (standardised mean difference (SMD)) in the three groups: haloperidol: SMD=2.278, 95% CI 1.836 to 2.719; ziprasidone: SMD=2.536, 95% CI 2.082 to 2.990; and clonazepam: SMD=1.360, 95% CI 0.127 to 2.593. The acceptability was assessed by the incidence of excessive sedation, which showed that ziprasidone and haloperidol were similar with both being superior to clonazepam (sucra: 0.3, 0.7 and 99.0). Ziprasidone had significantly less adverse effects than haloperidol in effects of extrapyramidal system (EPS) (=5.01, <0.001). There were no statistically significant differences between haloperidol and ziprasidone in tachycardia and abnormal ECG (=1.69, =0.091; =0.87, =0.386; respectively). Based on GRADE, the strength of the evidence for primary outcome was 'medium'.
Our results suggested that ziprasidone was more suitable than haloperidol and clonazepam in the treatment of agitation symptoms in Chinese patients with schizophrenia, according to the efficacy and acceptability of these three intramuscular injection medications.
激越在急性期精神分裂症患者中非常常见，抗精神病药物及氯硝西泮注射剂被广泛应用。关于这三种注射治疗方法疗效比较的网状Meta分析鲜有报道。
比较不同注射剂治疗中国精神分裂症患者激越症状的疗效及安全性。
检索截至2018年2月18日的PubMed、Embase、Web of Knowledge、Cochrane图书馆、万方数据、中国知网、中国生物医学文献数据库及维普数据库。两名评价员根据Cochrane评价组标准检索策略进行检索。采用《报告试验的统一标准》声明评估研究的方法学质量。使用STATA软件进行Meta分析。采用Cochrane推荐分级、评估、制定与评价（GRADE）方法评估证据强度。
网状Meta分析共纳入15项研究。其中11项研究比较了齐拉西酮与氟哌啶醇，4项研究比较了氟哌啶醇与氯硝西泮。结果显示，在治疗激越症状方面，齐拉西酮比氟哌啶醇和氯硝西泮更有效（表面排序曲线下面积：77.2、72.8和0）。三组的效应量（标准化均数差（SMD））分别为：氟哌啶醇：SMD = 2.278，95%CI为1.836至2.719；齐拉西酮：SMD = 2.536，95%CI为2.082至2.990；氯硝西泮：SMD = 1.360，95%CI为0.127至2.593。通过过度镇静发生率评估可接受性，结果显示齐拉西酮和氟哌啶醇相似，均优于氯硝西泮（表面排序曲线下面积：0.3、0.7和99.0）。在锥体外系反应方面，齐拉西酮的不良反应明显少于氟哌啶醇（χ² = 5.01，P < 0.001）。在心动过速和心电图异常方面，氟哌啶醇与齐拉西酮之间无统计学差异（χ² = 1.69，P = 0.091；χ² = 0.87，P = 0.386）。基于GRADE，主要结局的证据强度为“中等”。
根据这三种肌肉注射药物的疗效和可接受性，我们的结果表明，在中国精神分裂症患者激越症状的治疗中，齐拉西酮比氟哌啶醇和氯硝西泮更合适。
