Potkin Steven G, Gharabawi Georges M, Greenspan Andrew J, Mahmoud Ramy, Kosik-Gonzalez Colette, Rupnow Marcia F T, Bossie Cynthia A, Davidson Michael, Burtea Victoria, Zhu Young, Trivedi Jintendra K
University of California, Irvine, Orange, 92696, USA.
Schizophr Res. 2006 Jul;85(1-3):254-65. doi: 10.1016/j.schres.2006.03.027. Epub 2006 Jun 21.
This study compared the effects of atypical antipsychotics (risperidone or quetiapine) with placebo and with each other in recently exacerbated patients with schizophrenia requiring hospitalization.
This international, randomized, double-blind study included a 2-week monotherapy phase followed by a 4-week additive therapy phase. Recently exacerbated patients with schizophrenia or schizoaffective disorder (DSM-IV) were randomized (2:2:1) to risperidone (n = 153), quetiapine (n = 156), or placebo (n = 73). Target doses were 4 or 6 mg/day of risperidone and 400 or 600 mg/day of quetiapine by day 5, with the ability to increase to 600 or 800 mg/day of quetiapine on day 8. The main outcome measures were the total Positive and Negative Syndrome Scale (PANSS) and need for additional psychotropic medications.
Monotherapy Phase: The combined atypical antipsychotic group (n = 308) reached borderline superiority to placebo (n = 71) at the 2-week endpoint on mean change in total PANSS score (-24.1 +/- 1.2 and -20.2 +/- 2.0, respectively; p = 0.067). The change in the atypical group was driven by the improvement with risperidone (-27.7 +/- 1.5 vs. -20.2 +/- 2.0 with placebo, p < 0.01; and vs. -20.5 +/- 1.5 with quetiapine, p < 0.01); the improvement with quetiapine was similar to placebo, p = 0.879. Results were similar on other efficacy endpoints. Additive Therapy Phase: Additional psychotropics were prescribed to fewer (p < 0.01) risperidone (36%) than quetiapine (53%) or placebo patients (59%). The overall discontinuation rate was 18%, 26%, and 38%, respectively. Risperidone, compared with placebo, was associated with more parkinsonism, akathisia, plasma prolactin changes, and weight gain; while quetiapine was associated with more somnolence, sedation, dizziness, constipation, tachycardia, thyroid dysregulation, and weight gain.
While the combined atypical antipsychotic group did not experience greater improvements than the placebo group, risperidone, but not quetiapine, was significantly superior in all measured domains to placebo in the management of recently exacerbated hospitalized patients with schizophrenia or schizoaffective disorder, with no unexpected tolerability findings.
本研究比较了非典型抗精神病药物（利培酮或喹硫平）与安慰剂以及二者之间对于近期病情加重且需住院治疗的精神分裂症患者的疗效。
这项国际随机双盲研究包括一个为期2周的单药治疗阶段，随后是一个为期4周的联合治疗阶段。近期病情加重的精神分裂症或分裂情感性障碍（DSM-IV）患者被随机分组（2:2:1），分别接受利培酮（n = 153）、喹硫平（n = 156）或安慰剂（n = 73）治疗。至第5天时，利培酮的目标剂量为4或6毫克/天，喹硫平的目标剂量为400或600毫克/天，至第8天时喹硫平剂量可增至600或800毫克/天。主要疗效指标为阳性与阴性症状量表（PANSS）总分以及额外使用精神药物的需求。
单药治疗阶段：在第2周的终点，联合非典型抗精神病药物组（n = 308）在PANSS总分的平均变化方面达到了与安慰剂组（n = 71）接近显著的优势（分别为-24.1±1.2和-20.2±2.0；p = 0.067）。非典型药物组的变化主要由利培酮的改善所驱动（与安慰剂相比，-27.7±1.5 vs. -20.2±2.0，p < 0.01；与喹硫平相比，-20.5±1.5，p < 0.01）；喹硫平的改善与安慰剂相似，p = 0.879。在其他疗效终点上结果相似。联合治疗阶段：与喹硫平（53%）或安慰剂组患者（59%）相比，接受额外精神药物治疗的利培酮患者较少（p < 0.01）。总体停药率分别为18%、26%和38%。与安慰剂相比，利培酮与更多的帕金森症、静坐不能、血浆催乳素变化及体重增加相关；而喹硫平与更多的嗜睡、镇静、头晕、便秘、心动过速、甲状腺功能失调及体重增加相关。
虽然联合非典型抗精神病药物组的改善情况并不优于安慰剂组，但在治疗近期病情加重的住院精神分裂症或分裂情感性障碍患者时，利培酮在所有测量领域均显著优于安慰剂，而喹硫平则不然，且未发现意外的耐受性问题。
