Kumar A, Strech D
Cochrane Schizophrenia Group, Academic Unit of Psychiatry and Behavioural Sciences, 15 Hyde Terrace, Leeds, UK LS2 9LT.
Cochrane Database Syst Rev. 2005 Oct 19(4):CD005474. doi: 10.1002/14651858.CD005474.
Zuclopenthixol dihydrochloride, given orally, is commonly used for managing the signs and symptoms of schizophrenia.
To determine the effects of zuclopenthixol dhydrochloride for treatment of schizophrenia.
We searched the Cochrane Schizophrenia Group's register (December 2004). This register is compiled of methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. To identify further trials we also contacted a pharmaceutical company and authors of relevant studies.
We included all randomised controlled trials comparing zuclopenthixol dihydrocodine with antipsychotics or with placebo (or no intervention) for treatment of schizophrenia and/or schizophrenia-like psychoses.
We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed articles and extracted data. For dichotomous data we calculated relative risks (RR) and the 95% confidence intervals (CI) and the number needed to treat (NNT) or number needed to harm statistics. For continuous data we calculated weighted mean differences with 95% CIs for non-skewed data.
We included eighteen trials involving 1578 people. Two trials compared zuclopenthixol with placebo and neither reported global or mental state outcomes. People allocated zuclopenthixol did have increased risk of experiencing extraparamydal symptoms compared with placebo (n=64, RR 5.37, CI 1.12 to 29.34 NNH 2 CI 2 to 31). Ten short trials (total n=478) compared zuclopenthixol with other typical antipsychotics. Risk of being unchanged or worse was decreased by allocation to zuclopenthixol (n=357, 7 RCTs, RR 0.72 CI 0.53 to 0.98, NNT 10 CI 6 to 131). No findings suggest any clear difference between zuclopenthixol and other typical antipsycotics across a whole range of adverse effects, including movement disorders (n=280, 6 RCTs, RR needing additional antiparkinsonian medication 1.07 CI 0.86 to 1.33) and general agitation (n=162, 3 RCTs, RR needing treatment with hypnotic/sedative drugs 1.09 CI 0.76 to 1.56). Fewer people allocated zuclopenthixol left in the short term compared with those given other typical antipsychotics (n=424, 22% vs 30%, 8 RCTs, RR 0.70 CI 0.51 to 0.95, NNT 12 CI 7 to 67). Three short trials (total n=233) compared zuclopenthixol with atypical antipsychotics. Zuclopenthixol was associated with no greater risk of being unchanged or worse compared with risperidone (n=98, 1 RCT, RR 1.30 CI 0.80 to 2.11). People allocated zuclopenthixol were prescribed antiparkinsonian medication more frequently compared to those treated with risperidone (n=98, 1 RCT, RR 1.92 CI 1.12 to 3.28, NNH 3 CI 3 to 17). Weight gain was equal for people allocated zuclopenthixol and those given sulpiride (n=61, 1 RCT, WMD 1.60 CI 8.35 to 5.15). Many people left these short studies early (45% zuclopenthixol vs 30% risperidone, n=159, 2 RCTs, RR 1.48 CI 0.98 to 2.22). The two isomers of zuclopenthixol, when compared in four short studies (total n=140), did not result in clearly different outcomes.
AUTHORS' CONCLUSIONS: There is an indication that zuclopenthixol causes movement disorders, perhaps more so than the newer generation of drugs, though no more frequently than the older generation of antipsychotics. There is some suggestion from this review that oral zuclopenthixol may have some clinical advantage, at least in the short term, over other older drugs in terms of global state. If an older drug is going to be prescribed, zuclopenthixol dihydrochloride is a viable option but may be best taken with additional medication to offset movement disorders that occur in about half the people taking this drug. There is no information on service, functional, behavioural outcomes and important outcomes such as relapse, for such a widely used drug this would indicate the need for further studies. We feel that it should remain a choice in the treatment of those for whom older generation drugs are indicated.
口服二盐酸珠氯噻醇常用于控制精神分裂症的体征和症状。
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登记册（2004年12月）。该登记册通过对BIOSIS、CINAHL、学位论文摘要、EMBASE、LILACS、MEDLINE、PSYNDEX、PsycINFO、RUSSMED、Sociofile进行系统检索编制而成，并辅以对相关期刊和众多会议论文集的手工检索。为了识别更多试验，我们还联系了一家制药公司和相关研究的作者。
我们纳入了所有将二盐酸珠氯噻醇与抗精神病药物或安慰剂（或无干预）进行比较以治疗精神分裂症和/或精神分裂症样精神病的随机对照试验。
我们独立检查了文献引用和摘要，订购了论文，重新检查并对文章进行质量评估，然后提取数据。对于二分数据，我们计算了相对风险（RR）、95%置信区间（CI）以及治疗所需人数（NNT）或伤害所需人数统计量。对于连续数据，我们计算了非偏态数据的加权平均差及95%CI。
我们纳入了18项试验，涉及1578人。两项试验将珠氯噻醇与安慰剂进行了比较，均未报告整体或精神状态结果。与安慰剂相比，分配到珠氯噻醇组的人出现锥体外系症状的风险增加（n = 64，RR 5.37，CI 1.12至29.34，NNH 2 CI 2至31）。十项短期试验（共n = 478）将珠氯噻醇与其他传统抗精神病药物进行了比较。分配到珠氯噻醇组病情无变化或恶化的风险降低（n = 357，7项随机对照试验，RR 0.72，CI 0.53至0.98，NNT 10，CI 6至131）。没有研究结果表明在包括运动障碍（n = 280，6项随机对照试验，需要额外抗帕金森药物治疗的RR 1.07，CI 0.86至1.33）和一般激越（n = 162，3项随机对照试验，需要使用催眠/镇静药物治疗的RR 1.09，CI 0.76至1.56）在内的一系列不良反应方面，珠氯噻醇与其他传统抗精神病药物之间存在任何明显差异。与给予其他传统抗精神病药物的人相比，分配到珠氯噻醇组的人在短期内退出试验的人数更少（n = 424，22%对30%，8项随机对照试验，RR 0.70，CI [0.51，0.95]，NNT 12，CI 7至67）。三项短期试验（共n = 233）将珠氯噻醇与非典型抗精神病药物进行了比较。与利培酮相比，珠氯噻醇病情无变化或恶化的风险并未更高（n = 98，1项随机对照试验，RR 1.30，CI 0.80至2.11）。与接受利培酮治疗的人相比，分配到珠氯噻醇组的人更频繁地被处方抗帕金森药物（n = 98，1项随机对照试验，RR 1.92，CI 1.12至3.28，NNH 3，CI 3至17）。分配到珠氯噻醇组的人与给予舒必利组的人体重增加相同（n = 61，1项随机对照试验，WMD 1.60，CI -8.35至5.15）。许多人提前退出了这些短期研究（珠氯噻醇组45%，利培酮组30%，n = 159，2项随机对照试验，RR 1.48，CI 0.98至2.22）。在四项短期研究（共n = 140）中比较珠氯噻醇的两种异构体时，未得出明显不同的结果。
有迹象表明珠氯噻醇会导致运动障碍，可能比新一代药物更易导致，尽管不比老一代抗精神病药物更频繁。本综述表明，至少在短期内，口服珠氯噻醇在整体状态方面可能比其他老药具有一些临床优势。如果要处方老药，二盐酸珠氯噻醇是一个可行的选择，但可能最好同时服用其他药物以抵消约一半服用该药的人出现的运动障碍。对于这样一种广泛使用的药物，没有关于服务、功能、行为结果以及复发等重要结果的信息，这表明需要进一步研究。我们认为，对于那些适合使用老一代药物的患者，它仍应是一种治疗选择。
