Thornley B, Adams C E, Awad G
Green College, Woodstock Road, Oxford, UK, OX2 6HG.
Cochrane Database Syst Rev. 2000(2):CD000284. doi: 10.1002/14651858.CD000284.
Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for those with schizophrenia.
To evaluate the effects of chlorpromazine for schizophrenia in comparison to placebo.
Electronic searches of Biological Abstracts (1982-1995), The Cochrane Library (1999, Issue 2), The Cochrane Schizophrenia Group's Register (October 1999), EMBASE (1980-1995), MEDLINE (1966-1995), PsycLIT (1974-1995) were undertaken. References of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were contacted.
Randomised controlled trials relating to people with schizophrenia, and non-affective serious/chronic mental illness irrespective of mode of diagnosis evaluating chlorpromazine (any dose) versus placebo. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care.
Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted by BT with CA and GA independently checking a 10% sample for reliability. Dichotomous data were analysed using random effects relative risk (RR) and the 95% confidence interval around this was estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics (NNH) were calculated. Continuous data were excluded if more than 50% of people were lost to follow up, but, where possible, weighted mean difference was calculated. Sensitivity analyses have not been undertaken for this version of the review.
Over 1000 electronic records were inspected. The review currently mentions 202 papers in its Excluded Studies section and 45 studies in its Included Studies table. Six papers await assessment. Chlorpromazine reduces relapse over six months to two years (RR 0.65 CI 0.5-0.9, NNT 3 CI 2.5-4) and there is convincing evidence from trials that it promotes a global improvement in a person's symptoms and functioning (RR 0.76 CI 0.7-0.9, NNT 7 CI 5-10) although the placebo response is also considerable (nearly 40%). Fewer people allocated to chlorpromazine leave trials early (RR 0.76 CI 0.6-1.1). There are many adverse effects. Chlorpromazine is clearly sedating (RR 2.4 CI 1.7-3.3, NNH 6 CI 4-8), it increases a person's chances of experiencing acute movement disorders (RR 3.1 CI 1.3-7.6, NNH 24 CI 14-77), parkinsonism (RR 2.6 CI 1.2-5.4, NNH 10 CI 8-16) and fits (RR 2.4 CI 0.4-16). Amongst other things it clearly causes a lowering of blood pressure with accompanying dizziness (RR 1.9 CI 1. 3-2.6, NNH 12 CI 8-22) and considerable increases in weight (RR 4.4 CI 2.1-9, NNH 3 CI 2-5).
REVIEWER'S CONCLUSIONS: This review will confirm much that clinicians and recipients of care already know but provides quantification to support clinical impression. Despite the humbling 40% improvement rate in those who were allocated to placebo, chlorpromazine's global position as the 'benchmark' treatment of those with psychoses is not threatened by this review. Chlorpromazine, in common use for nearly half a century, is a well established but imperfect treatment. Judicious use of this best available evidence should lead to better informed decisions both by carers and those with psychotic illnesses.
20世纪50年代配制的氯丙嗪仍是精神分裂症患者的一种基准治疗药物。
评估氯丙嗪与安慰剂相比治疗精神分裂症的效果。
对《生物学文摘》（1982 - 1995年）、《考克兰图书馆》（1999年第2期）、考克兰精神分裂症研究小组注册库（1999年10月）、《医学文摘数据库》（1980 - 1995年）、《医学索引》（1966 - 1995年）、《心理学文摘》（1974 - 1995年）进行了电子检索。对所有已识别研究的参考文献进行检索以获取更多试验引用。联系了制药公司和试验作者。
与精神分裂症患者以及非情感性严重/慢性精神疾病患者相关的随机对照试验，无论诊断方式如何，评估氯丙嗪（任何剂量）与安慰剂。感兴趣的主要结局是死亡、暴力行为、总体改善、复发以及对治疗的满意度。
由评审人员独立检查文献引用，并在可能的情况下检查摘要，整理文献、再次检查并进行质量评估。由BT提取数据，CA和GA独立检查10%的样本以确保可靠性。使用随机效应相对危险度（RR）分析二分数据，并估计其95%置信区间（CI）。尽可能计算治疗所需人数（NNT）或伤害所需人数（NNH）统计量。如果超过50%的人失访，则排除连续数据，但在可能的情况下计算加权平均差。本版综述未进行敏感性分析。
检查了1000多条电子记录。本综述在其“排除研究”部分目前提及202篇论文，在其“纳入研究”表中提及45项研究。6篇论文等待评估。氯丙嗪可降低6个月至2年的复发率（RR 0.65，CI 0.5 - 0.9，NNT 3，CI 2.5 - 4），并且试验中有令人信服的证据表明它能促进患者症状和功能的整体改善（RR 0.76，CI 0.7 - 0.9，NNT 7，CI 5 - 10），尽管安慰剂反应也相当可观（近40%）。分配接受氯丙嗪治疗的人中提前退出试验的人数较少（RR 0.76，CI 0.6 - 1.1）。有许多不良反应。氯丙嗪明显具有镇静作用（RR 2.4，CI 1.7 - 3.3，NNH 6，CI 4 - 8），它增加了患者出现急性运动障碍的几率（RR 3.1，CI 1.3 - 7.6，NNH 24，CI 14 - 77）、帕金森症（RR 2.6，CI 1.2 - 5.4，NNH 10，CI 8 - 16）和抽搐（RR 2.4，CI 0.4 - 16）。除此之外，它明显会导致血压降低并伴有头晕（RR 1.9，CI 1.3 - 2.6，NNH 12，CI 8 - 22）以及体重显著增加（RR 4.4，CI 2.1 - 9，NNH 3，CI 2 - 5）。
本综述将证实许多临床医生和护理接受者已经知晓的内容，但提供了量化数据以支持临床印象。尽管分配接受安慰剂治疗的患者有40%的令人印象深刻的改善率，但氯丙嗪作为精神病患者“基准”治疗药物的总体地位并未受到本综述的威胁。氯丙嗪已普遍使用近半个世纪，是一种既定但并不完美的治疗方法。明智地使用这些现有最佳证据应能使护理人员和患有精神疾病的人做出更明智的决策。
