Bryan Edward J, Purcell Marie Ann, Kumar Ajit
Sheffield Health and Social Care, NHS Foundation Trust, Fulwood House, Old Fulwood Road, Sheffield, UK, S10 3TH.
Cochrane Database Syst Rev. 2017 Nov 16;11(11):CD005474. doi: 10.1002/14651858.CD005474.pub2.
Oral zuclopenthixol dihydrochloride (Clopixol) is an anti-psychotic treatment for people with psychotic symptoms, especially those with schizophrenia. It is associated with neuroleptic malignant syndrome, a prolongation of the QTc interval, extra-pyramidal reactions, venous thromboembolism and may modify insulin and glucose responses.
To determine the effects of zuclopenthixol dihydrochloride for treatment of schizophrenia.
We searched the Cochrane Schizophrenia Group's Trials Register (latest search 09 June 2015). There were no language, date, document type, or publication status limitations for inclusion of records in the register.
All randomised controlled trials (RCTs) focusing on zuclopenthixol dihydrochloride for schizophrenia. We included trials meeting our inclusion criteria and reporting useable data.
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
We included 20 trials, randomising 1850 participants. Data were reported for 12 comparisons, predominantly for the short term (up to 12 weeks) and inpatient populations. Overall risk of bias for included studies was low to unclear.Data were unavailable for many of our pre-stated outcomes of interest. No data were available, across all comparisons, for death, duration of stay in hospital and general functioning.Zuclopenthixol dihydrochloride versus: 1. placeboMovement disorders (EPSEs) were similar between groups (1 RCT, n = 28, RR 6.07 95% CI 0.86 to 43.04 very low-quality evidence). There was no clear difference in numbers leaving the study early (2 RCTs, n = 100, RR 0.29, 95% CI 0.01 to 6.60, very low-quality evidence). 2. chlorpromazineNo clear differences were found for the outcomes of global state (average CGI-SI endpoint score) (1 RCT, n = 60, MD 0.00, 95% CI -0.49 to 0.49) or movement disorders (EPSEs) (3 RCTs, n = 199, RR 0.94, 95% CI 0.61 to 1.45), both very low-quality evidence. More people left the study early for any reason from the zuclopenthixol group (6 RCTs, n = 766, RR 0.54, 95% CI 0.36 to 0.81, low-quality evidence). 3. chlorprothixeneThere was no clear difference in numbers leaving the study early for any reason (1 RCT, n = 20, RR 1.00, 95% CI 0.34 to 2.93, very low-quality evidence). 4. clozapineNo useable data were presented. 5. haloperidolNo clear differences between treatment groups were found for the outcomes global state score (average CGI endpoint score) (1 RCT, n = 49, MD 0.13, 95% CI -0.30 to 0.55) or leaving the study early (2 RCTs, n = 141, RR 0.99, 95% CI 0.72 to 1.35), both very low-quality evidence. 6. perphenazineThose receiving zuclopenthixol were more likely to require medication in the short term for EPSEs than perphenazine (1 RCT, n = 50, RR 1.90, 95% CI 1.12 to 3.22, very low-quality evidence). Similar numbers left the study early (2 RCTs, n = 104, RR 0.63, 95% CI 0.27 to 1.47, very low-quality evidence). 7. risperidoneThose receiving zuclopenthixol were more likely to require medications for EPSEs than risperidone (1 RCT, n = 98,RR 1.92, 95% CI 1.12 to 3.28, very low quality evidence). There was no clear difference in numbers leaving the study early ( 3 RCTs, n = 154, RR 1.30, 95% CI 0.84 to 2.02) or in mental state (average PANSS total endpoint score) (1 RCT, n = 25, MD -3.20, 95% CI -7.71 to 1.31), both very low-quality evidence). 8. sulpirideNo clear differences were found for global state (average CGI endpoint score) ( 1 RCT, n = 61, RR 1.18, 95% CI 0.49 to 2.85, very low-quality evidence), requiring hypnotics/sedatives (1 RCT, n = 61, RR 0.60, 95% CI 0.27 to 1.32, very low-quality evidence) or leaving the study early (1 RCT, n = 61, RR 2.07 95% CI 0.97 to 4.40, very low-quality evidence). 9. thiothixeneNo clear differences were found for the outcomes of 'global state (average CGI endpoint score) (1 RCT, n = 20, RR 0.50, 95% CI 0.17 to 1.46) or leaving the study early (1 RCT, n = 20, RR 0.57, 95% CI 0.24 to 1.35), both very low-quality evidence). 10. trifluoperazineNo useable data were presented. 11. zuclopenthixol depotThere was no clear difference in numbers leaving the study early (1 RCT, n = 46, RR 1.95, 95% CI 0.36 to 10.58, very low-quality evidence). 12. Zuclopenthixol dihydrochloride (cis z isomer) versus zuclopenthixol (cis z/trans e isomer)There were no clear differences in reported side-effects ( 1 RCT, n = 57, RR 1.34, 95% CI 0.82 to 2.18, very low-quality evidence) and in numbers leaving the study early (4 RCTs, n = 140, RR 2.15, 95% CI 0.49 to 9.41, very low-quality evidence).
AUTHORS' CONCLUSIONS: Zuclopenthixol dihydrochloride appears to cause more EPSEs than clozapine, risperidone or perphenazine, but there was no difference in EPSEs when compared to placebo or chlorpromazine. Similar numbers required hypnotics/sedatives when zuclopenthixol dihydrochloride was compared to sulpiride, and similar numbers of reported side-effects were found when its isomers were compared. The other comparisons did not report adverse-effect data.Reported data indicate zuclopenthixol dihydrochloride demonstrates no difference in mental or global states compared to placebo, chlorpromazine, chlorprothixene, clozapine, haloperidol, perphenazine, sulpiride, thiothixene, trifluoperazine, depot and isomers. Zuclopenthixol dihydrochloride, when compared with risperidone, is favoured when assessed using the PANSS in the short term, but not in the medium term.The data extracted from the included studies are mostly equivocal, and very low to low quality, making it difficult to draw firm conclusions. Prescribing practice is unlikely to change based on this meta-analysis. Recommending any particular course of action about side-effect medication other than monitoring, using rating scales and clinical assessment, and prescriptions on a case-by-case basis, is also not possible.There is a need for further studies covering this topic with more antipsychotic comparisons for currently relevant outcomes.
口服二盐酸珠氯噻醇（氯哌噻吨）是一种用于治疗精神病性症状患者，尤其是精神分裂症患者的抗精神病药物。它与神经阻滞剂恶性综合征、QTc间期延长、锥体外系反应、静脉血栓栓塞有关，并且可能会改变胰岛素和葡萄糖反应。
确定二盐酸珠氯噻醇治疗精神分裂症的效果。
我们检索了Cochrane精神分裂症研究组的试验注册库（最新检索日期为2015年6月9日）。纳入注册库记录时没有语言、日期、文献类型或发表状态的限制。
所有聚焦于二盐酸珠氯噻醇治疗精神分裂症的随机对照试验（RCT）。我们纳入了符合我们纳入标准并报告了可用数据的试验。
我们独立提取数据。对于二分结局，我们基于意向性分析计算风险比（RR）及其95%置信区间（CI）。对于连续性数据，我们估计组间均值差（MD）及其95%CI。我们采用随机效应模型进行分析。我们评估纳入研究的偏倚风险，并使用GRADE创建“结果总结”表。
我们纳入了20项试验，随机分配了1850名参与者。报告了12项比较的数据，主要针对短期（长达12周）和住院患者群体。纳入研究的总体偏倚风险为低到不明确。我们预先设定的许多感兴趣的结局没有可用数据。在所有比较中，均没有关于死亡、住院时间和总体功能的数据。
两组之间的运动障碍（锥体外系反应）相似（1项RCT，n = 28，RR 6.07，95%CI 0.86至43.04，极低质量证据）。因任何原因提前退出研究的人数没有明显差异（2项RCT，n = 100，RR 0.29，95%CI 0.01至6.60，极低质量证据）。
在总体状态结局（平均CGI - SI终点评分）（1项RCT，n = 60，MD 0.00，95%CI -0.49至0.49）或运动障碍（锥体外系反应）（3项RCT，n = 199，RR 0.94，95%CI 0.61至1.45）方面未发现明显差异，两者均为极低质量证据。从珠氯噻醇组因任何原因提前退出研究的人数更多（6项RCT，n = 766，RR 0.54，95%CI 0.36至0.81，低质量证据）。
因任何原因提前退出研究的人数没有明显差异（1项RCT，n = 20，RR 1.00，95%CI 0.34至2.93，极低质量证据）。
未呈现可用数据。
在总体状态评分结局（平均CGI终点评分）（1项RCT，n = 49，MD 0.13，95%CI -0.30至0.55）或提前退出研究方面（2项RCT，n = 141，RR 0.99，95%CI 0.72至1.35），治疗组之间未发现明显差异，两者均为极低质量证据。
接受珠氯噻醇治疗的患者在短期内因锥体外系反应需要用药的可能性高于奋乃静（1项RCT，n = 50，RR 1.90，95%CI 1.12至3.22，极低质量证据）。提前退出研究的人数相似（2项RCT，n = 104，RR 0.63，95%CI 0.27至1.47，极低质量证据）。
接受珠氯噻醇治疗的患者因锥体外系反应需要用药的可能性高于利培酮（1项RCT，n = 98，RR 1.92，95%CI 1.12至3.28，极低质量证据）。提前退出研究的人数没有明显差异（3项RCT，n = 154，RR 1.30，95%CI 0.84至2.02）或精神状态（平均PANSS总分终点评分）（1项RCT，n = 25，MD -3.20，95%CI -7.71至1.31），两者均为极低质量证据）。
在总体状态（平均CGI终点评分）（1项RCT，n = 61，RR 1.18，95%CI 0.49至2.85，极低质量证据）、需要使用催眠药/镇静剂方面（1项RCT，n = 61，RR 0.60，95%CI 0.27至1.32，极低质量证据）或提前退出研究方面（1项RCT，n = 61，RR 2.07，95%CI 0.97至4.40，极低质量证据）未发现明显差异。
在“总体状态（平均CGI终点评分）”结局（1项RCT，n = 20，RR 0.50，95%CI 0.17至1.46）或提前退出研究方面（1项RCT，n = 20，RR 0.57，95%CI 0.24至1.35）未发现明显差异，两者均为极低质量证据。
未呈现可用数据。
提前退出研究的人数没有明显差异（1项RCT，n = 46，RR 1.95，95%CI 0.36至10.58，极低质量证据）。
在报告的副作用方面（1项RCT，n = 57，RR 1.34，95%CI 0.82至2.18，极低质量证据）和提前退出研究的人数方面（4项RCT，n = 140，RR 2.15，95%CI 0.49至9.41，极低质量证据）没有明显差异。
二盐酸珠氯噻醇似乎比氯氮平、利培酮或奋乃静引起更多的锥体外系反应，但与安慰剂或氯丙嗪相比，锥体外系反应没有差异。与舒必利相比，使用二盐酸珠氯噻醇时需要催眠药/镇静剂的人数相似，并且在比较其异构体时发现报告的副作用人数相似。其他比较未报告不良反应数据。报告的数据表明，与安慰剂、氯丙嗪、氯普噻吨、氯氮平、氟哌啶醇、奋乃静、舒必利、替沃噻吨、三氟拉嗪、长效制剂和异构体相比，二盐酸珠氯噻醇在精神状态或总体状态方面没有差异。在短期内使用PANSS评估时，与利培酮相比，二盐酸珠氯噻醇更受青睐，但在中期则不然。从纳入研究中提取的数据大多模棱两可，质量极低到低，难以得出确凿结论。基于此荟萃分析，处方实践不太可能改变。除了监测、使用评定量表和临床评估以及逐案开处方外，就副作用药物推荐任何特定的行动方案也是不可能的。需要进一步研究该主题，对目前相关结局进行更多抗精神病药物的比较。
