Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder:: an open randomised clinical trial
Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder:: an open randomised clinical trial
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DOI：
10.1016/s0140-6736(08)60486-9
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发表时间：
2008-03-01
期刊：
影响因子：
168.9
通讯作者：
Grobbee, Diederick E.
中科院分区：
文献类型：
--
作者：
Kahn, Rene S.;Fleischhacker, W. Wolfgang;Grobbee, Diederick E.
背景
第二代抗精神病药物于十多年前被引入用于治疗精神分裂症；然而，与第一代抗精神病药物相比，它们所谓的临床疗效仍存在争议。我们旨在比较第二代抗精神病药物与低剂量氟哌啶醇在首发精神分裂症中的疗效。
方法
我们在14个国家的50个地点进行了一项氟哌啶醇与第二代抗精神病药物的开放随机对照试验。符合条件的患者年龄在18 - 40岁之间，符合精神分裂症、分裂样精神障碍或分裂情感性障碍的诊断标准。498名患者通过基于网络的在线系统被随机分配到氟哌啶醇组（每天1 - 4毫克；n = 103）、氨磺必利组（每天200 - 800毫克；n = 104）、奥氮平组（每天5 - 20毫克；n = 105）、喹硫平组（每天200 - 750毫克；n = 104）或齐拉西酮组（每天40 - 160毫克；n = 82）；随访时间为1年。主要结局指标是全因治疗中断。患者及其治疗医生对所分配的治疗未设盲。采用意向性治疗分析。本研究已注册为国际标准随机对照试验，编号为ISRCTN68736636。
结果
在12个月内因任何原因中断治疗的患者数量，氟哌啶醇组为63例（卡普兰 - 迈耶估计值为72%），氨磺必利组为32例（40%），奥氮平组为30例（33%），喹硫平组为51例（53%），齐拉西酮组为31例（45%）。与氟哌啶醇相比，氨磺必利（风险比[HR] 0.37，[95%置信区间0.24 - 0.57]）、奥氮平（HR 0.28 [0.18 - 0.43]）、喹硫平（HR 0.52 [0.35 - 0.76]）和齐拉西酮（HR 0.51 [0.32 - 0.81]）的任何原因中断治疗的风险更低。然而，所有组的症状减轻情况几乎相同，约为60%。
解释
这项务实的试验表明，对首发精神分裂症进行至少1年具有临床意义的抗精神病治疗是可行的。然而，我们不能得出第二代药物比氟哌啶醇更有效的结论，因为中断治疗率不一定与症状改善情况一致。
资助
阿斯利康、辉瑞、赛诺菲 - 安万特
Background Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia; however, their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated. We aimed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol, in first-episode schizophrenia.Methods We did an open randomised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites, in 14 countries. Eligible patients were aged 18-40 years, and met diagnostic criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. 498 patients were randomly assigned by a web-based online system to haloperidol (1-4 mg per day; n=103), amisulpride (200-800 mg per day; n=104), olanzapine (5-20 mg per day; n=105), quetiapine (200-750 mg per day; n=104), or ziprasidone (40-160 mg per day; n=82); follow-up was at 1 year. The primary outcome measure was all-cause treatment discontinuation. Patients and their treating physicians were not blinded to the assigned treatment. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN68736636.Findings The number of patients who discontinued treatment for any cause within 12 months was 63 (Kaplan-Meier estimate 72%) for haloperidol, 32 (40%) for amisulpride, 30 (33%) for olanzapine, 51 (53%) for quetiapine, and 31 (45%) for ziprasidone. Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride (hazard ratio [HR] 0 . 37, [95% Cl 0. 24-0.57]), olanzapine (HR 0 . 28 [0.18-0.43]), quetiapine (HR 0 . 52 [0 . 35-0.76]), and ziprasidone (HR 0 . 51 [0.32-0.81]). However, symptom reductions were virtually the same in all the groups, at around 60%.Interpretation This pragmatic trial suggests that clinically meaningful antipsychotic treatment of first-episode of schizophrenia is achievable, for at least 1 year. However, we cannot conclude that second-generation drugs are more efficacious than is haloperidol, since discontinuation rates are not necessarily consistent with symptomatic improvement.Funding AstraZeneca, Pfizer, Sanofi-Aventis.