Leucht Stefan, Wahlbeck Kristian, Hamann Johannes, Kissling Werner
Klinik und Poliklinik für Psychiatrie und Psychotherapie der Technischen Universität München, Klinikum rechts der Isar, München, Germany.
Lancet. 2003 May 10;361(9369):1581-9. doi: 10.1016/S0140-6736(03)13306-5.
The clearest advantage of new generation, atypical antipsychotics is a reduced risk of extrapyramidal side-effects (EPS), compared with conventional compounds. These findings might have been biased by the use of the high-potency antipsychotic haloperidol as a comparator in most of the trials. We aimed to establish whether the new drugs induce fewer EPS than low-potency conventional antipsychotics.
We did a meta-analysis of all randomised controlled trials in which new generation antipsychotics had been compared with low-potency (equivalent or less potent than chlorpromazine) conventional drugs. We included studies that met quality criteria A or B in the Cochrane Collaboration Handbook, and assessed quality with the Jadad scale. The primary outcome of interest was the number of patients who had at least one EPS. We used risk differences and 95% CIs as measures of effect size.
We identified 31 studies with a total of 2320 participants. Of the new generation drugs, only clozapine was associated with significantly fewer EPS (RD=-0.15, 95% CI -0.26 to -0.4, p=0.008) and higher efficacy than low-potency conventional drugs. Reduced frequency of EPS seen with olanzapine was of borderline significance (-0.15, -0.31 to -0.01, p=0.07). Only one inconclusive trial of amisulpride, quetiapine, and risperidone and no investigations of ziprasidone and sertindole were identified, but some evidence indicates that zotepine and remoxipride do not lead to fewer EPS than low-potency antipsychotics. Mean doses less than 600 mg/day of chlorpromazine or its equivalent had no higher risk of EPS than new generation drugs. As a group, new generation drugs were moderately more efficacious than low-potency antipsychotics, largely irrespective of the comparator doses used.
Optimum doses of low-potency conventional antipsychotics might not induce more EPS than new generation drugs. Potential advantages in efficacy of the new generation drugs should be a factor in clinical treatment decisions to use these rather than conventional drugs.
与传统化合物相比，新一代非典型抗精神病药物最明显的优势是锥体外系副作用（EPS）风险降低。在大多数试验中，这些结果可能因使用高效能抗精神病药物氟哌啶醇作为对照而存在偏差。我们旨在确定这些新药是否比低效能传统抗精神病药物诱发的EPS更少。
我们对所有将新一代抗精神病药物与低效能（等效或效能低于氯丙嗪）传统药物进行比较的随机对照试验进行了荟萃分析。我们纳入了符合Cochrane协作手册质量标准A或B的研究，并使用Jadad量表评估质量。感兴趣的主要结局是至少发生一次EPS的患者数量。我们使用风险差异和95%置信区间作为效应大小的衡量指标。
我们确定了31项研究，共有2320名参与者。在新一代药物中，只有氯氮平与显著更少的EPS相关（风险差异=-0.15，95%置信区间-0.26至-0.4，p=0.008），且比低效能传统药物疗效更高。奥氮平观察到的EPS频率降低具有临界显著性（-0.15，-0.31至-0.01，p=0.07）。仅确定了一项关于氨磺必利、喹硫平和利培酮的不确定试验，未发现关于齐拉西酮和舍吲哚的研究，但一些证据表明，氯氮平和瑞莫必利导致的EPS并不比低效能抗精神病药物少。氯丙嗪或其等效物平均日剂量低于600毫克时，EPS风险并不高于新一代药物。总体而言，新一代药物比低效能抗精神病药物疗效略高，在很大程度上与所使用的对照剂量无关。
低效能传统抗精神病药物的最佳剂量可能不会比新一代药物诱发更多的EPS。新一代药物在疗效方面的潜在优势应成为临床治疗决策中使用这些药物而非传统药物的一个因素。
