Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, 260 Stetson St., Suite 3224, Cincinnati, OH 45219, USA.
J Psychiatr Res. 2013 May;47(5):670-7. doi: 10.1016/j.jpsychires.2013.01.020. Epub 2013 Feb 17.
Despite the availability of established antipsychotic agents for the treatment of schizophrenia, continued unmet needs exist for effective medications with lower adverse-effect burden. The present study evaluated the efficacy, safety, and tolerability of treatment with the atypical antipsychotic lurasidone for patients with an acute exacerbation of schizophrenia. Patients were randomized to 6 weeks of double-blind treatment with lurasidone 40 mg/day, 80 mg/day, or 120 mg/day, or placebo. Changes in Positive and Negative Syndrome Scale (PANSS) scores were evaluated using mixed-model repeated-measures (MMRM) analysis. Vital signs, laboratory parameters, extrapyramidal symptoms, and electrocardiogram were assessed. Treatment with lurasidone 80 mg/day resulted in significantly greater improvement in PANSS total score compared with placebo (-23.4 versus -17.0; p < 0.05) at study endpoint (MMRM); lurasidone 40 mg/day and 120 mg/day achieved clinically meaningful overall PANSS score reductions from baseline (-19.2 and -20.5), but not significant separation from placebo. Differences between all lurasidone groups and placebo for changes in laboratory parameters and electrocardiographic measures were minimal. Weight gain ≥ 7% occurred in 8.2% of patients receiving lurasidone and 3.2% receiving placebo. Modest increases in prolactin (median increase, 0.7 ng/mL) and extrapyramidal symptoms were observed following treatment with lurasidone compared with placebo. Akathisia was the most commonly reported adverse event with lurasidone (17.6%, versus 3.1% with placebo). In this study, in which a large placebo response was observed, lurasidone 80 mg/day, but not 40 mg/day or 120 mg/day, was statistically superior to placebo in treating acute exacerbation of chronic schizophrenia. All lurasidone doses were generally well tolerated.
尽管有多种已确立的抗精神病药物可用于治疗精神分裂症，但仍存在对不良反应负担较低的有效药物的未满足需求。本研究评估了新型抗精神病药鲁拉西酮治疗精神分裂症急性加重患者的疗效、安全性和耐受性。患者随机接受 6 周的双盲治疗，分别接受鲁拉西酮 40mg/天、80mg/天或 120mg/天或安慰剂治疗。采用混合模型重复测量（MMRM）分析评估阳性和阴性综合征量表（PANSS）评分的变化。评估生命体征、实验室参数、锥体外系症状和心电图。与安慰剂相比，鲁拉西酮 80mg/天治疗在研究终点时（MMRM）可显著改善 PANSS 总分（-23.4 与-17.0；p＜0.05）；鲁拉西酮 40mg/天和 120mg/天可使 PANSS 总分从基线显著降低（-19.2 和-20.5），但与安慰剂无显著差异。与安慰剂相比，所有鲁拉西酮组的实验室参数和心电图测量值的变化差异最小。鲁拉西酮组 8.2%的患者和安慰剂组 3.2%的患者体重增加≥7%。与安慰剂相比，鲁拉西酮治疗后催乳素（中位数增加 0.7ng/ml）和锥体外系症状适度增加。与安慰剂相比，鲁拉西酮最常见的不良反应是静坐不能（17.6%，安慰剂组为 3.1%）。在这项观察到大的安慰剂反应的研究中，与安慰剂相比，鲁拉西酮 80mg/天但不是 40mg/天或 120mg/天在治疗慢性精神分裂症急性加重方面具有统计学优势。所有鲁拉西酮剂量通常均具有良好的耐受性。
