Komossa Katja, Rummel-Kluge Christine, Hunger Heike, Schmid Franziska, Schwarz Sandra, Duggan Lorna, Kissling Werner, Leucht Stefan
Klinik und Poliklinik für Psychiatrie und Psychotherapie, Technische Universität München Klinikum rechts der Isar, Moehlstrasse 26, München, Germany, 81675.
Cochrane Database Syst Rev. 2010 Mar 17;2010(3):CD006654. doi: 10.1002/14651858.CD006654.pub2.
In many countries of the industrialised world second generation ("atypical") antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics.
To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis.
We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine 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.
The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole, clozapine, quetiapine, risperidone or ziprasidone). The overall attrition from the included studies was considerable (49.2%) leaving the interpretation of results problematic.Olanzapine improved the general mental state (PANSS total score) more than aripiprazole (2 RCTs, n=794, WMD -4.96 CI -8.06 to -1.85), quetiapine (10 RCTs, n=1449, WMD -3.66 CI -5.39 to -1.93), risperidone (15 RCTs, n=2390, WMD -1.94 CI -3.31 to -0.58) and ziprasidone (4 RCTs, n=1291, WMD -8.32 CI -10.99 to -5.64), but not more than amisulpride or clozapine. This somewhat better efficacy was confirmed by fewer participants in the olanzapine groups leaving the studies early due to inefficacy of treatment compared to quetiapine (8 RCTs, n=1563, RR 0.56 CI 0.44 to 0.70, NNT 11 CI 6 to 50), risperidone (14 RCTs, n=2744, RR 0.78 CI 0.62 to 0.98, NNT 50 CI 17 to 100) and ziprasidone (5 RCTs, n=1937, RR 0.64 CI 0.51 to 0.79, NNT 17, CI 11 to 33).Fewer participants in the olanzapine group than in the quetiapine (2 RCTs, n=876, RR 0.56 CI 0.41 to 0.77, NNT 11 CI 7 to 25) and ziprasidone (2 RCTs, n=766, RR 0.65 CI 0.45 to 0.93, NNT 17 CI 9 to 100) treatment groups, but not in the clozapine group (1 RCT, n=980, RR 1.28 CI 1.02 to 1.61, NNH not estimable), had to be re-hospitalised in the trials.Except for clozapine, all comparators induced less weight gain than olanzapine (olanzapine compared to amisulpride: 3 RCTs, n=671, WMD 2.11kg CI 1.29kg to 2.94kg; aripiprazole: 1 RCT, n=90, WMD 5.60kg CI 2.15kg to 9.05kg; quetiapine: 7 RCTs, n=1173, WMD 2.68kg CI 1.10kg to 4.26kg; risperidone: 13 RCTs, n=2116, WMD 2.61kg CI 1.48kg to 3.74kg; ziprasidone: 5 RCTs, n=1659, WMD 3.82kg CI 2.96kg to 4.69kg). Associated problems such as glucose and cholesterol increase were usually also more frequent in the olanzapine group.Other differences in adverse effects were less well documented. Nevertheless, olanzapine may be associated with slightly more extrapyramidal side effects than quetiapine (use of antiparkinson medication (6 RCTs, n=1090, RR 2.05 CI 1.26 to 3.32, NNH 25 CI 14 to 100), but less than risperidone (use of antiparkinson medication 13 RCTs, n=2599, RR 0.78 CI 0.65 to 0.95, NNH 17 CI 9 to 100) and ziprasidone (use of antiparkinson medication 4 RCTs, n=1732, RR 0.70 CI 0.50 to 0.97, NNH not estimable). It may also increase prolactin somewhat more than aripiprazole, clozapine and quetiapine, but clearly less so than risperidone (6 RCTs, n=1291, WMD -22.84 CI -27.98 to -17.69).
AUTHORS' CONCLUSIONS: Olanzapine may be a somewhat more efficacious drug than some other second generation antipsychotic drugs. This small superiority in efficacy needs to be weighed against a larger weight gain and associated metabolic problems than most other second generation antipsychotic drugs, except clozapine. These conclusions are tentative due to the large number of people leaving the studies early which possibly limits the validity of the findings. Further large, well-designed trials are necessary to establish the relative effects of different second generation antipsychotic drugs.
在许多工业化国家，第二代（“非典型”）抗精神病药物已成为精神分裂症患者的一线药物治疗选择。各种第二代抗精神病药物的效果是否存在差异以及差异程度如何，这一问题仍存在争议。在本综述中，我们研究了奥氮平的疗效和耐受性与其他第二代抗精神病药物相比有何不同。
评估奥氮平与其他非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。
我们纳入了所有至少采用单盲（评分者盲）设计的随机试验，这些试验比较了口服奥氮平与口服氨磺必利、阿立哌唑、氯氮平、喹硫平、利培酮、齐拉西酮或佐替平治疗精神分裂症或精神分裂症样精神病患者的效果。
我们独立提取数据。对于二分数据，我们基于随机效应模型，在意向性分析的基础上计算相对风险（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/伤害人数（NNT/NNH）。对于连续数据，我们同样基于随机效应模型计算加权平均差（WMD）。
本综述目前包括50项研究和9476名参与者，提供了六项比较的数据（奥氮平与氨磺必利、阿立哌唑、氯氮平、喹硫平、利培酮或齐拉西酮的比较）。纳入研究中的总体失访率相当高（49.2%），这使得结果的解释存在问题。奥氮平在改善总体精神状态（PANSS总分）方面比阿立哌唑（2项随机对照试验；n = 794；WMD -4.96；CI -8.06至-1.85）、喹硫平（10项随机对照试验；n = 1449；WMD -3.66；CI -5.39至-1.93）、利培酮（15项随机对照试验；n = 2390；WMD -1.94；CI -3.31至-0.58）和齐拉西酮（4项随机对照试验；n = 1291；WMD -8.32；CI -10.99至-5.64）更有效，但不比氨磺必利或氯氮平更有效。与喹硫平（8项随机对照试验；n = 1563；RR 0.56；CI 0.44至0.70；NNT 11；CI 6至50）、利培酮（14项随机对照试验；n = 2744；RR 0.78；CI 0.62至0.98；NNT 50；CI 17至100）和齐拉西酮（5项随机对照试验；n = 1937；RR 0.64；CI 0.51至0.79；NNT 17；CI 11至33）相比，奥氮平组中因治疗无效而提前退出研究的参与者较少，这证实了其在疗效上略胜一筹。与喹硫平（2项随机对照试验；n = 876；RR 0.56；CI 0.41至0.77；NNT 11；CI 7至25）和齐拉西酮（2项随机对照试验；n = 766；RR 0.65；CI 0.45至0.93；NNT 17；CI 9至100）治疗组相比，奥氮平组中需要再次住院的参与者较少，但与氯氮平组（1项随机对照试验；n = 980；RR 1.28；CI 1.02至1.61；NNH无法估计）相比并非如此。除氯氮平外，所有对照药物引起的体重增加均少于奥氮平（奥氮平与氨磺必利比较：3项随机对照试验；n = 671；WMD 2.11kg；CI 1.29kg至2.94kg；阿立哌唑：1项随机对照试验；n = 90；WMD 5.60kg；CI 2.15kg至9.05kg；喹硫平：7项随机对照试验；n = 1173；WMD 2.68kg；CI 1.10kg至4.26kg；利培酮：13项随机对照试验；n = 2116；WMD 2.61kg；CI 1.48kg至3.74kg；齐拉西酮：5项随机对照试验；n = 1659；WMD 3.82kg；CI 2.96kg至4.69kg）。奥氮平组中血糖和胆固醇升高等相关问题通常也更频繁。其他不良反应的差异记录较少。然而，奥氮平可能比喹硫平引起的锥体外系副作用略多（使用抗帕金森药物：6项随机对照试验；n = 1090；RR 2.05；CI 1.26至3.32；NNH 25；CI 14至100），但比利培酮（使用抗帕金森药物：13项随机对照试验；n = 2599；RR 0.78；CI 0.65至0.95；NNH 17；CI 9至100）和齐拉西酮（使用抗帕金森药物：4项随机对照试验；n = 1732；RR 0.70；CI 0.50至0.97；NNH无法估计）少。它可能也比阿立哌唑、氯氮平和喹硫平使催乳素升高得更多，但明显比利培酮少（6项随机对照试验；n = 1291；WMD -22.84；CI -27.98至-17.69）。
奥氮平可能比其他一些第二代抗精神病药物更有效。这种疗效上的微小优势需要与比大多数其他第二代抗精神病药物（氯氮平除外）更大的体重增加及相关代谢问题相权衡。由于大量人员提前退出研究，可能限制了研究结果的有效性，这些结论具有一定的试探性。需要进一步开展大规模、设计良好的试验，以确定不同第二代抗精神病药物的相对效果。
