Department of Psychiatry, University of Colorado Anschutz Medical Campus, 13199 E. Montview Blvd, Suite 330, MS F550, Aurora, CO 80045, USA; Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, 13199 E. Montview Blvd, Suite 330, MS F550, Aurora, CO 80045, USA.
Department of Psychiatry and Behavioral Sciences, New York Medical College, 20 Hospital Road, Valhalla, NY 10595, USA.
Gen Hosp Psychiatry. 2017 Jul;47:75-82. doi: 10.1016/j.genhosppsych.2017.05.002. Epub 2017 May 5.
This post hoc analysis evaluated the effect of lurasidone on agitation in acutely ill patients with schizophrenia.
Patient-level data were pooled from five 6-week, randomized, double-blind, placebo-controlled studies of fixed-dose, once-daily, oral lurasidone (40, 80, 120, or 160 mg/d). Agitation was assessed with the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) score, utilizing a mixed model for repeated measurement analysis.
In patients with higher levels of agitation at baseline (PANSS-EC score≥14; n=773), lurasidone was associated with significantly greater improvement in least-squares (LS) mean PANSS-EC scores versus placebo at Day 3/4 (-1.6 vs -1.0; p<0.05), Day 7 (-2.3 vs -1.6; p<0.05), and at Week 6 endpoint (-5.5 vs -3.8; p<0.001; effect size=0.43). In patients with lower agitation at baseline (PANSS-EC score<14; n=754), LS mean PANSS-EC score change was significantly greater for lurasidone compared with placebo at Day 7 (-0.8 vs -0.1; p<0. 01) through Week 6 endpoint (-1.9 vs -0.9; p<0.001; effect size=0.31). Higher doses of lurasidone were notably more effective than lower doses in patients with more severe agitation at study baseline.
In this pooled analysis of 5 short-term studies, lurasidone provided early and sustained reduction in agitation, assessed using the PANSS-EC score, in patients with an acute exacerbation of schizophrenia. Higher doses of lurasidone were particularly effective in patients with more severe agitation at study baseline. Overall, these results suggest that lurasidone may be a useful treatment option for patients exhibiting agitation associated with acute psychotic symptoms of schizophrenia. ClinicalTrials.gov Identifiers: NCT00088634 (Study D1050196); NCT00549718 (Study D1050229), NCT00615433 (Study D1050231); NCT00790192 (Study D1050233). Study D1050006 was completed prior to the requirement to register trials.
本事后分析评估了鲁拉西酮对急性精神病患者激越症状的疗效。
本项研究汇总了 5 项为期 6 周、随机、双盲、安慰剂对照、固定剂量、每日一次口服鲁拉西酮（40、80、120 或 160mg/d）的研究中患者水平的数据。使用重复测量混合模型评估阳性和阴性综合征量表兴奋分量表（PANSS-EC）评分评估激越。
在基线时激越程度较高（PANSS-EC 评分≥14；n=773）的患者中，与安慰剂相比，鲁拉西酮在第 3/4 天（LS 均值变化：-1.6 对-1.0；p<0.05）、第 7 天（-2.3 对-1.6；p<0.05）和第 6 周末（-5.5 对-3.8；p<0.001；效应量=0.43）时 LS 均值 PANSS-EC 评分改善更显著。在基线时激越程度较低（PANSS-EC 评分<14；n=754）的患者中，与安慰剂相比，鲁拉西酮在第 7 天（LS 均值变化：-0.8 对-0.1；p<0.01）至第 6 周末（-1.9 对-0.9；p<0.001；效应量=0.31）时 LS 均值 PANSS-EC 评分变化更显著。基线时激越程度更严重的患者使用较高剂量的鲁拉西酮治疗，疗效更为显著。
在这 5 项短期研究的汇总分析中，鲁拉西酮可早期并持续改善精神分裂症急性发作患者的激越症状，PANSS-EC 评分显示，使用鲁拉西酮治疗的患者，激越症状改善显著。在基线时激越程度更严重的患者中，高剂量鲁拉西酮的疗效尤为显著。总之，这些结果表明，鲁拉西酮可能是治疗伴有精神分裂症急性精神病症状的激越患者的一种有效治疗选择。临床试验注册：NCT00088634（研究 D1050196）；NCT00549718（研究 D1050229）；NCT00615433（研究 D1050231）；NCT00790192（研究 D1050233）。研究 D1050006 在要求进行临床试验注册之前已完成。
