Bhattacharjee Jayanti, El-Sayeh Hany George G
Psychiatry, NHS, Bierley Lane, Bierley, Bradford, UK, BD4 6AD.
Cochrane Database Syst Rev. 2008 Jul 16;2008(3):CD006617. doi: 10.1002/14651858.CD006617.pub3.
Aripiprazole is a relatively new antipsychotic drug, said to be the prototype of a new third generation of antipsychotics; the so-called dopamine-serotonin system stabilisers. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of typical antipsychotics.
To evaluate the effects of aripiprazole compared with other typical antipsychotics for people with schizophrenia and schizophrenia-like psychoses.
We searched the Cochrane Schizophrenia Group Trials Register (November 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies for further trials. We contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information.
We included all randomised trials comparing aripiprazole with typical antipsychotics in people with schizophrenia or schizophrenia-like psychosis.
We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. We have contacted representatives of Bristol Myers Squibb pharmaceuticals (UK) for additional data.
We included nine randomised trials involving 3122 people comparing aripiprazole with typical antipsychotic drugs. None of the studies reported on relapse - our primary outcome of interest. Attrition from studies was high and data reporting poor. Participants given aripiprazole were comparable to those receiving typical drugs in improving global state and mental state. Aripiprazole provided a significant advantage over typical antipsychotics in terms of fewer occurrences of extra-pyramidal symptom (n=968, 3 RCT, RR 0.46 CI 0.3 to 0.9, NNT 13 CI 17 to 10), and particularly akathisia (n=897, 3 RCT, RR 0.39 CI 0.3 to 0.6, NNT 11 CI 14 to 9). Fewer participants given aripiprazole developed hyperprolactinaemia (n=300, 1 RCT, RR 0.07 CI 0.03 to 0.2, NNT 2 CI 3 to 1). Aripiprazole presented a lesser risk of sinus tachycardia (n=289, 1 RCT, RR 0.09 CI 0.01 to 0.8, NNT 22 CI 63 to 13) and blurred vision (n=308, 1 RCT, RR 0.19 CI 0.1 to 0.7, NNT 14 CI 25 to 10); but enhanced risk of occurrence of dizziness (n=957, 3 RCT, RR 1.88 CI 1.1 to 3.2, NNH 20 CI 33 to 14) and nausea (n=957, 3 RCT, RR 3.03 CI 1.5 to 6.1, NNH 17 CI 25 to 13). Attrition rates were high in both groups, although significantly more participants in the aripiprazole group completed the study in the long term (n=1294, 1 RCT, RR 0.81 CI 0.8 to 0.9 NNT 8 CI 5 to 14).
AUTHORS' CONCLUSIONS: Aripiprazole differs little from typical antipsychotic drugs with respect to efficacy, however it presents significant advantages in terms of tolerability. Clearly reported pragmatic short, medium and long term randomised controlled trials are required to replicate and validate these findings and determine the position of aripiprazole in everyday clinical practice.
阿立哌唑是一种相对较新的抗精神病药物,被认为是新一代第三代抗精神病药物的原型;即所谓的多巴胺 - 5-羟色胺系统稳定剂。在本综述中,我们研究了阿立哌唑与典型抗精神病药物在疗效和耐受性方面的差异。
评估阿立哌唑与其他典型抗精神病药物相比,对精神分裂症和精神分裂症样精神病患者的疗效。
我们检索了Cochrane精神分裂症研究组试验注册库(2007年11月),该注册库基于对BIOSIS、CENTRAL、CINAHL、EMBASE、MEDLINE和PsycINFO的定期检索。我们检查了所有已识别研究的参考文献以查找进一步的试验。我们联系了相关制药公司、药物审批机构和试验作者以获取更多信息。
我们纳入了所有将阿立哌唑与典型抗精神病药物用于精神分裂症或精神分裂症样精神病患者的随机试验。
我们独立提取数据。对于二分数据,我们基于意向性分析,采用随机效应模型计算相对风险(RR)及其95%置信区间(CI)。在适当情况下,我们计算治疗所需人数/伤害所需人数(NNT/NNH)。对于连续性数据,我们同样基于随机效应模型计算加权平均差(WMD)。我们已联系百时美施贵宝制药公司(英国)的代表以获取更多数据。
我们纳入了9项随机试验,涉及3122名将阿立哌唑与典型抗精神病药物进行比较的患者。没有研究报告复发情况——这是我们感兴趣的主要结局。研究中的失访率很高,数据报告质量较差。接受阿立哌唑治疗的参与者在改善整体状态和精神状态方面与接受典型药物治疗的参与者相当。在锥体外系症状发生次数方面,阿立哌唑比典型抗精神病药物具有显著优势(n = 968,3项随机对照试验,RR 0.46,CI 0.3至0.9,NNT 13,CI 17至10),尤其是静坐不能(n = 897,3项随机对照试验,RR 及相关数值)。接受阿立哌唑治疗的参与者发生高催乳素血症的人数较少(n = 300,1项随机对照试验,RR 0.07,CI 0.03至0.2,NNT 2,CI 3至1)。阿立哌唑出现窦性心动过速(n = 289,1项随机对照试验,RR 0.09,CI 0.01至0.8,NNT 22,CI 63至13)和视力模糊(n = 308,1项随机对照试验,RR 0.19,CI 0.1至0.7,NNT 14,CI 25至10)的风险较低;但出现头晕(n = 957,3项随机对照试验,RR 1.88,CI 1.1至3.2,NNH 20,CI 33至14)和恶心(n = 957,3项随机对照试验,RR 3.03,CI 1.5至6.1,NNH 及相关数值)的风险增加。两组的失访率都很高,尽管从长期来看,阿立哌唑组完成研究的参与者明显更多(n = 1294,1项随机对照试验,RR 0.81,CI 0.8至0.9,NNT 8,CI 5至14)。
阿立哌唑在疗效方面与典型抗精神病药物差异不大,然而在耐受性方面具有显著优势。需要进行明确报告的实用短期、中期和长期随机对照试验来重复和验证这些发现,并确定阿立哌唑在日常临床实践中的地位。