Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis
Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis
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DOI：
10.1016/s0140-6736(13)60733-3
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发表时间：
2013-09-14
期刊：
影响因子：
168.9
通讯作者：
Davis, John M.
中科院分区：
文献类型：
--
作者：
Leucht, Stefan;Cipriani, Andrea;Davis, John M.
背景 对于精神分裂症的治疗应首选哪种抗精神病药物的问题存在争议，传统的成对荟萃分析无法提供基于随机证据的层次结构。我们的目的是整合现有证据，以创建抗精神病药物的比较疗效、全因停药风险和主要副作用的层次结构。方法我们对随机对照试验进行了贝叶斯框架、多治疗荟萃分析（使用直接和间接比较），以比较 15 种抗精神病药物和安慰剂在急性治疗中的作用。 精神分裂症。我们检索了 Cochrane 精神分裂症组的专门注册库、Medline、Embase、Cochrane 对照试验中央注册库和 ClinicalTrials.gov，查找截至 2012 年 9 月 1 日发布的报告。搜索结果由美国食品和药物管理局网站的报告以及制药公司索取的数据进行了补充。对精神分裂症或相关疾病患者进行的盲法、随机对照试验是合格的。我们排除了在具有主要阴性症状、伴随医疗疾病或治疗抵抗的患者中进行的试验，以及在稳定患者中进行的试验。七个结果的数据由两名评审员独立提取。主要结果是疗效，通过症状的平均总体变化来衡量。我们还检查了全因停药、体重增加、锥体外系副作用、催乳素增加、QTc 延长和镇静。结果我们确定了 212 项合适的试验，数据涉及 43 049 名参与者。所有药物均比安慰剂更有效。 95%可信区间的标准化平均差为：氯氮平0.88、0.73-1.03；氨磺必利 0.66、0.53-0.78；奥氮平0.59、0.53-0.65；利培酮0.56、0.50-0.63；帕潘立酮0.50、0.39-0.60；佐替平 0.49、0.31-0.66；氟哌啶醇0.45、0.39-0.51；喹硫平 0.44、0.35-0.52；阿立哌唑 0.43、0.34-0.52；舍吲哚 0.39、0.26-0.52；齐拉西酮 0.39、0.30-0.49；氯丙嗪0.38、0.23-0.54；阿塞那平 0.38、0.25-0.51；鲁拉西酮 0.33、0.21-0.45；和伊潘立酮0.33、0.22-0.43。与安慰剂相比，全因停药的比值比范围从最好的药物（氨磺必利）的 0.43 到最差的药物（氟哌啶醇）的 0.80；对于锥体外系副作用 0.30（氯氮平）至 4.76（氟哌啶醇）；镇静作用为 1.42（氨磺必利）至 8.82（氯氮平）。与安慰剂相比，体重增加的标准化平均差异从最佳药物（氟哌啶醇）的 -0.09 到最差药物（奥氮平）的 -0.74，催乳素增加 0.22（阿立哌唑）到 -1.30（帕潘立酮），QTc 延长 0.10（鲁拉西酮）到 -0.90（舍吲哚）。在去除安慰剂组或氟哌啶醇组后，或者在荟萃回归和敏感性分析中考虑剂量、退出百分比、盲法程度、制药行业赞助、研究持续时间、长期性和发表年份时，疗效结果没有显着变化。 解释 抗精神病药物在副作用方面存在显着差异，在疗效方面也存在微小但显着的差异。我们的研究结果挑战了将抗精神病药物直接分为第一代和第二代的方法。相反，不同领域的层次结构应该有助于临床医生根据个体患者的需求调整抗精神病药物的选择。精神卫生政策制定者和修订临床实践指南时应考虑这些发现。
Background The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy based on the randomised evidence. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs.Methods We did a Bayesian-framework, multiple-treatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's specialised register, Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search results were supplemented by reports from the US Food and Drug Administration website and by data requested from pharmaceutical companies. Blinded, randomised controlled trials of patients with schizophrenia or related disorders were eligible. We excluded trials done in patients with predominant negative symptoms, concomitant medical illness, or treatment resistance, and those done in stable patients. Data for seven outcomes were independently extracted by two reviewers. The primary outcome was efficacy, as measured by mean overall change in symptoms. We also examined all-cause discontinuation, weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, and sedation.Findings We identified 212 suitable trials, with data for 43 049 participants. All drugs were significantly more effective than placebo. The standardised mean differences with 95% credible intervals were: clozapine 0.88, 0.73-1.03; amisulpride 0.66, 0.53-0.78; olanzapine 0.59, 0.53-0.65; risperidone 0.56, 0.50-0.63; paliperidone 0.50, 0.39-0.60; zotepine 0.49, 0.31-0.66; haloperidol 0.45, 0.39-0.51; quetiapine 0.44, 0.35-0.52; aripiprazole 0.43, 0.34-0.52; sertindole 0.39, 0.26-0.52; ziprasidone 0.39, 0.30-0.49; chlorpromazine 0.38, 0.23-0.54; asenapine 0.38, 0.25-0.51; lurasidone 0.33, 0.21-0.45; and iloperidone 0.33, 0.22-0.43. Odds ratios compared with placebo for all-cause discontinuation ranged from 0.43 for the best drug (amisulpride) to 0.80 for the worst drug (haloperidol); for extrapyramidal side-effects 0.30 (clozapine) to 4.76 (haloperidol); and for sedation 1.42 (amisulpride) to 8.82 (clozapine). Standardised mean differences compared with placebo for weight gain varied from -0.09 for the best drug (haloperidol) to -0.74 for the worst drug (olanzapine), for prolactin increase 0.22 (aripiprazole) to -1.30 (paliperidone), and for QTc prolongation 0.10 (lurasidone) to -0.90 (sertindole). Efficacy outcomes did not change substantially after removal of placebo or haloperidol groups, or when dose, percentage of withdrawals, extent of blinding, pharmaceutical industry sponsorship, study duration, chronicity, and year of publication were accounted for in meta-regressions and sensitivity analyses.Interpretation Antipsychotics differed substantially in side-effects, and small but robust differences were seen in efficacy. Our findings challenge the straightforward classification of antipsychotics into first-generation and second-generation groupings. Rather, hierarchies in the different domains should help clinicians to adapt the choice of antipsychotic drug to the needs of individual patients. These findings should be considered by mental health policy makers and in the revision of clinical practice guidelines.