Ziprasidone, haloperidol and clonazepam intramuscular administration in the treatment of agitation symptoms in Chinese patients with schizophrenia: A network meta-analysis

BACKGROUND: 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. AIM: To compare the efficacy and safety of various injections for agitation symptoms in Chinese patients with schizophrenia. METHODS: 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. RESULTS: 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) (z=5.01, p<0.001). There were no statistically significant differences between haloperidol and ziprasidone in tachycardia and abnormal ECG (z=1.69, p=0.091; z=0.87, p=0.386; respectively). Based on GRADE, the strength of the evidence for primary outcome was ‘medium’. CONCLUSION: 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.