Rummel C, Hamann J, Kissling W, Leucht S
Klinik und Poliklinik für Psychiatrie und Psychotherapie der Technischen Universität München, Klinikum rechts der Isar, Möhlstr. 26, Munich, Germany, 81675.
Cochrane Database Syst Rev. 2003;2003(4):CD004410. doi: 10.1002/14651858.CD004410.
BACKGROUND: The new generation antipsychotics are associated with a lower risk of adverse effects compared with drugs such as haloperidol. Many treatment guidelines recommend the use of new generation ('atypical') antipsychotic drugs for people with a first episode of schizophrenia. OBJECTIVES: To examine the effects of the new generation antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses. SEARCH STRATEGY: The reviewers searched the Cochrane Schizophrenia Group's register (March 2002) and the included and excluded studies tables of relevant Cochrane reviews, references of all relevant studies, contacted industry and authors of relevant studies to identify further trials. SELECTION CRITERIA: Randomised clinical trials comparing new generation antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, sulpiride, ziprasidone, zotepine) with conventional antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by three reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data but excluded them if loss to follow up was greater than 50%. For homogeneous dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences (WMD). MAIN RESULTS: We include two short-term studies (total n=266), one of which was a report of a sub-group of a larger study. One compared risperidone with an average of 6 mg/day haloperidol and the other olanzapine with an average of 11 mg/day haloperidol. Compared with olanzapine, significantly more people receiving haloperidol left the study early (n=83, 1 RCT, RR 0.43 CI 0.3 to 0.7, NNH 3 CI 2 to 8). This was not so for the risperidone versus haloperidol comparison (n=183, 1 RCT, RR=0.7 CI 0.4 to 1.1). In terms of global effects, studies reported no differences between risperidone and haloperidol (n=183, RR not much improved 1.0 CI 0.6 to 1.5), and olanzapine and the same control (n=83, RR needing at least one dose of benzodiazepine 0.8 CI 0.5 to 1.1). More people allocated to olanzapine had clinically significant improvement in mental state compared with those given haloperidol (n=83, RR no 'clinically significant improvement' 0.45 CI 0.3 to 0.7, NNH 3 CI 2 to 6). In the risperidone study, however, no such difference was apparent (n=183, RR 'no clinically significant improvement in mental state' 0.85 CI 0.6 to 1.2). Significantly more people given haloperidol (4-16mg) experienced at least one adverse event when compared with risperidone (4-16mg) (n=183, RR 0.9 CI 0.8 to 0.98, NNH 8 CI 4 to 50). Use of anticholinergic medication for extrapyramidal adverse events was less prevalent for people allocated either olanzapine (n=83, RR 0.3 CI 0.2 to 0.7, NNH 4 CI 2 to 14) or risperidone (n=183, RR 0.7 CI 0.5 to 0.9, NNH 4 CI 3 to 9) compared with those given haloperidol. There are no data at all on outcomes such as compliance, cost, social and cognitive functioning, relapse, rehospitalisation, or quality of life. There are no medium to long-term data. Eight ongoing studies may provide more information. REVIEWER'S CONCLUSIONS: The results of this review are inconclusive. Whether the use of new generation antipsychotics really makes the treatment less off putting and enhances long-term compliance is unclear. Pragmatic, well-designed and reported long-term trials would be useful to answer this question.
背景:与氟哌啶醇等药物相比,新一代抗精神病药物的不良反应风险较低。许多治疗指南推荐对首次发作的精神分裂症患者使用新一代(“非典型”)抗精神病药物。 目的:研究新一代抗精神病药物对首次发作的精神分裂症或类精神分裂症精神病患者的疗效。 检索策略:综述作者检索了Cochrane精神分裂症研究组注册库(2002年3月)以及相关Cochrane综述的纳入和排除研究列表、所有相关研究的参考文献,联系了相关研究的制药企业和作者以确定更多试验。 选择标准:比较新一代抗精神病药物(氨磺必利、氯氮平、奥氮平、喹硫平、利培酮、舒必利、齐拉西酮、佐替平)与传统抗精神病药物用于首次发作的精神分裂症或类精神分裂症精神病患者的随机临床试验。 数据收集与分析:三位综述作者独立检查文献引用,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。我们独立提取数据,但如果失访率超过50%则将其排除。对于同质二分数据,我们在意向性分析的基础上计算相对危险度(RR)、95%置信区间(CI),并在适当情况下计算需治疗人数(NNT)。对于连续数据,综述作者计算加权均数差(WMD)。 主要结果:我们纳入了两项短期研究(共266例),其中一项是一项较大规模研究的亚组报告。一项研究将利培酮与平均每日6毫克氟哌啶醇进行比较,另一项将奥氮平与平均每日毫克氟哌啶醇进行比较。与奥氮平相比,接受氟哌啶醇治疗的患者中提前退出研究的人数显著更多(83例,1项随机对照试验,RR 0.43,CI 0.3至0.7,NNH 3,CI 2至8)。利培酮与氟哌啶醇的比较中未出现这种情况(183例,1项随机对照试验,RR = 0.7,CI 0.4至1.1)。在整体疗效方面,研究报告利培酮与氟哌啶醇之间无差异(183例,RR改善不多,1.0,CI 0.6至1.5),奥氮平与同一对照之间也无差异(83例,RR需要至少一剂苯二氮卓类药物,0.8,CI 0.5至1.1)。与接受氟哌啶醇治疗的患者相比,分配接受奥氮平治疗的患者中精神状态有临床显著改善的人数更多(83例,RR无“临床显著改善”,0.45,CI 0.3至0.7,NNH 3,CI 2至6)。然而,在利培酮研究中,未出现这种差异(183例,RR“精神状态无临床显著改善”,0.85,CI 0.6至1.2)。与利培酮(4 - 16毫克)相比,接受氟哌啶醇(4 - 16毫克)治疗的患者中经历至少一次不良事件的人数显著更多(183例,RR 0.9 CI 0.8至0.98,NNH 8,CI 4至50)。与接受氟哌啶醇治疗的患者相比,分配接受奥氮平(83例,RR 0.3,CI 0.2至0.7,NNH 4,CI 2至14)或利培酮(183例,RR 0.7,CI 0.5至0.9,NNH 4,CI 3至9)治疗的患者因锥体外系不良事件使用抗胆碱能药物的情况较少。在依从性、成本、社会和认知功能、复发、再次住院或生活质量等结局方面完全没有数据。没有中长期数据。八项正在进行的研究可能会提供更多信息。 综述作者结论:本综述结果尚无定论。使用新一代抗精神病药物是否真的能使治疗更易接受并提高长期依从性尚不清楚。实用、设计良好且报告规范的长期试验将有助于回答这个问题。
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