Clozapine versus other atypical antipsychotics for schizophrenia.
Clozapine versus other atypical antipsychotics for schizophrenia.
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DOI：
10.1002/14651858.cd006633.pub2
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发表时间：
2010-11-10
影响因子：
8.4
通讯作者：
Leucht, Stefan
中科院分区：
文献类型：
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作者：
Asenjo Lobos, Claudia;Komossa, Katja;Rummel-Kluge, Christine;Hunger, Heike;Schmid, Franziska;Schwarz, Sandra;Leucht, Stefan
氯氮平是一种非典型的抗精神病药物，在治疗难治性精神分裂症方面表现出上级优势，其引起的运动障碍较少。然而，氯氮平会引起严重的血液疾病，如粒细胞缺乏症，这可能是致命的。目前有许多新的抗精神病药物已开发的目的是找到一个更好的耐受性和上级的有效性。比较氯氮平与其他非典型抗精神病药（如氨磺必利、阿立哌唑、奥氮平、奎替利、利培酮、舍吲哚、齐拉西酮和佐替平）治疗精神分裂症和分裂样精神病的临床疗效。我们检索了科克伦精神分裂症组注册（2007年6月）和所有纳入的随机对照试验的参考文献列表。我们还人工检索了与氯氮平联合用药策略相关的适当期刊和会议记录，并联系了相关制药公司。所有相关的随机、至少单盲试验，比较氯氮平与其他非典型抗精神病药，任何剂量和口服制剂，用于精神分裂症或相关疾病患者。我们独立选择试验并提取数据。对于二分数据，我们基于随机效应模型计算相对风险（RR）及其95%置信区间（CI）。我们计算了需要治疗/伤害的数量（NNT/NNH）。对于连续数据，我们基于随机效应模型再次计算平均差（MD）。该综述目前包括27项盲法随机对照试验，涉及3099名受试者。12项随机对照试验比较了氯氮平与奥氮平，5项与奎替鲁，9项与利培酮，1项与齐拉西酮，2项与佐替平。这些研究的结果偏高（总体为30.1%），导致结果的解释存在问题。由于不良反应，氯氮平的脱落率高于奥氮平（9项RCT，n=1674，RR 1.60 CI 1.07 - 2.40，NNT 25 CI 15 - 73）和利培酮（6项RCT，n=627，RR 1.88 CI 1.11 - 3.21，NNT 16 CI 9 - 59）。氯氮平组因无效而提前退出试验的受试者少于利培酮组（6个RCT，n=627，RR 0.40 CI 0.23 ~ 0.70，NNT 11 CI 7 ~ 21），提示氯氮平有一定的疗效。在改善参与者的一般精神状态方面，氯氮平比佐替平更有效（BPRS总分：1个随机对照试验，n=59，MD-6.00 CI-9.83至-2.17），但并不总是比奥氮平、奎硫平、利培酮和齐拉西酮更有效。氯氮平与奥氮平、利培酮在精神分裂症阳性或阴性症状方面无显著性差异。根据来自中国的两项研究，奎替鲁比氯氮平对阴性症状更有效（2项RCT，n=142，MD 2.23 CI 0.99 - 3.48）。氯氮平产生的锥体外系副作用略少于利培酮（使用抗帕金森药物：6项RCT，n=304，RR 0.39 CI 0.22 - 0.68，NNT 7 CI 5 - 18）和佐替平（n=59，RR 0.05 CI 0.00 - 0.86，NNT 3 CI 2 - 5）。与奥氮平组相比，氯氮平组中更多的参与者表现出白色血细胞减少，与奥氮平、利培酮和奎替卡松组相比，更多的多涎和镇静，与奥氮平和利培酮组相比，更多的癫痫发作。此外，氯氮平产生了重要的体重增加，这是利培酮所没有的。不良反应的其他差异记录较少，应重复，例如，氯氮平没有改变催乳素水平，而奥氮平，利培酮和佐替平;与奎替鲁相比，氯氮平产生更高的心电图（ECG）改变的发生率;与奎替鲁和利培酮相比，氯氮平产生更高的甘油三酯水平升高。其他应重复的研究结果是：氯氮平改善社会功能低于利培酮，与奥氮平相比，氯氮平组有更少的参与者必须住院以避免自杀企图。其他重要的结果，如服务使用，认知功能，对护理或生活质量的满意度很少报告。氯氮平可能比佐替平和利培酮更有效，但需要进一步的试验来证实这一发现。氯氮平与其他第二代抗精神病药物的不良反应有更明显的不同，副作用特征可能是根据临床情况和患者偏好选择治疗的关键。其他重要结果的数据，如认知功能，生活质量，死亡或服务使用目前基本上缺失，使得进一步的大型和精心设计的试验是必要的。同样重要的是要考虑到，大量的人提前离开研究限制了我们的研究结果的有效性和解释。
Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness. To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses. We searched the Cochrane Schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies. All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders. We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a random-effects model. The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation of results problematic. Clozapine had a higher attrition rate due to adverse effects than olanzapine (9 RCTs, n=1674, RR 1.60 CI 1.07 to 2.40, NNT 25 CI 15 to 73) and risperidone (6 RCTs, n=627, RR 1.88 CI 1.11 to 3.21, NNT 16 CI 9 to 59). Fewer participants in the clozapine groups left the trials early due to inefficacy than risperidone (6 RCTs, n=627, RR 0.40 CI 0.23 to 0.70, NNT 11 CI 7 to 21), suggesting a certain higher efficacy of clozapine. Clozapine was more efficacious than zotepine in improving the participants general mental state (BPRS total score: 1 RCT, n=59, MD −6.00 CI −9.83 to −2.17), but not consistently more than olanzapine, quetiapine, risperidone and ziprasidone. There was no significant difference between clozapine and olanzapine or risperidone in terms of positive or negative symptoms of schizophrenia. According to two studies from China quetiapine was more efficacious for negative symptoms than clozapine (2 RCTs, n=142, MD 2.23 CI 0.99 to 3.48). Clozapine produced somewhat fewer extrapyramidal side-effects than risperidone (use of antiparkinson medication: 6 RCTs, n=304, RR 0.39 CI 0.22 to 0.68, NNT 7 CI 5 to 18) and zotepine (n=59, RR 0.05 CI 0.00 to 0.86, NNT 3 CI 2 to 5). More participants in the clozapine group showed decreased white blood cells than those taking olanzapine, more hypersalivation and sedation than those on olanzapine, risperidone and quetiapine and more seizures than people on olanzapine and risperidone. Also clozapine produced an important weight gain not seen with risperidone. Other differences in adverse effects were less documented and should be replicated, for example, clozapine did not alter prolactin levels whereas olanzapine, risperidone and zotepine did; compared with quetiapine, clozapine produced a higher incidence of electrocardiogram (ECG) alterations; and compared with quetiapine and risperidone clozapine produced a higher increase of triglyceride levels. Other findings that should be replicated were: clozapine improved social functioning less than risperidone and fewer participants in the clozapine group had to be hospitalised to avoid suicide attempts compared to olanzapine. Other important outcomes such as service use, cognitive functioning, satisfaction with care or quality of life were rarely reported. Clozapine may be a little more efficacious than zotepine and risperidone but further trials are required to confirm this finding. Clozapine differs more clearly in adverse effects from other second generation antipsychotics and the side-effect profile could be key in the selection of treatment depending on the clinical situation and a patient’s preferences. Data on other important outcomes such as cognitive functioning, quality of life, death or service use are currently largely missing, making further large and well-designed trials necessary. It is also important to take into account that the large number of people leaving the studies early limits the validity and interpretation of our findings.