Citrome Leslie, Weiden Peter J, McEvoy Joseph P, Correll Christoph U, Cucchiaro Josephine, Hsu Jay, Loebel Antony
1Department of Psychiatry & Behavioral Sciences,New York Medical College,Valhalla,New York,USA.
2Department of Psychiatry,University of Illinois at Chicago,Chicago,Illinois,USA.
CNS Spectr. 2014 Aug;19(4):330-9. doi: 10.1017/S109285291300093X. Epub 2013 Dec 16.
To evaluate the long-term safety and tolerability of lurasidone in schizophrenia and schizoaffective disorder patients switched to lurasidone.
Patients in this multicenter, 6-month open-label, flexible-dose, extension study had completed a core 6-week randomized trial in which clinically stable, but symptomatic, outpatients with schizophrenia or schizoaffective disorder were switched to lurasidone. Patients started the extension study on treatment with the same dose of lurasidone taken at study endpoint of the 6-week core study; following this, lurasidone was flexibly dosed (40-120 mg/day), if clinically indicated, starting on Day 7 of the extension study. The primary safety endpoints were the proportion of patients with treatment emergent adverse events (AEs), serious AEs, or who discontinued due to AEs. Secondary endpoints included metabolic variables and measures of extrapyramidal symptoms and akathisia, as well as the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), and the Calgary Depression Scale for Schizophrenia (CDSS). The study was conducted from August 2010 to November 2011.
Of the 198 patients who completed the 6-week core study, 149 (75.3%) entered the extension study and 148 received study medication. A total of 98 patients (65.8%) completed the 6-month extension study. Lurasidone 40, 80, and 120 mg were the modal daily doses for 19 (12.8%), 65 (43.9%), and 64 (43.2%) of patients, respectively. Overall mean (SD) daily lurasidone dose was 102.0 mg (77.1). The most commonly reported AEs were insomnia (13 patients [8.8%]), nausea (13 patients [8.8%]), akathisia (12 patients [8.1%]), and anxiety (9 patients [6.1%]). A total of 16 patients (10.8%) had at least one AE leading to discontinuation from the study. Consistent with prior studies of lurasidone, there was no signal for clinically relevant adverse changes in body weight, lipids, glucose, insulin, or prolactin. Movement disorder rating scales did not demonstrate meaningful changes. Treatment failure (defined as any occurrence of discontinuation due to insufficient clinical response, exacerbation of underlying disease, or AE) was observed for 19 patients (12.8% of patients entering) and median time to treatment failure was 58 days (95% CI 22-86). The discontinuation rate due to any cause was 50/148 (33.8%), and median time to discontinuation was 62 days (95% CI 30-75). The mean PANSS total score, mean CGI-S score, and mean CDSS score decreased consistently from core study baseline across extension visits, indicating an improvement in overall condition.
In this 6-month, open-label extension study, treatment with lurasidone was generally well-tolerated with sustained improvement in efficacy measures observed in outpatients with schizophrenia or schizoaffective disorder who had switched to lurasidone from a broad range of antipsychotic agents.
评估鲁拉西酮用于从其他药物转换而来的精神分裂症和分裂情感性障碍患者的长期安全性和耐受性。
在这项多中心、为期6个月的开放标签、灵活剂量的延长期研究中，患者已完成一项为期6周的核心随机试验，在该试验中，临床症状稳定但仍有症状的精神分裂症或分裂情感性障碍门诊患者被转换为使用鲁拉西酮治疗。患者在6周核心研究的终点时以相同剂量的鲁拉西酮开始延长期研究治疗；此后，根据临床指征，从延长期研究的第7天开始灵活调整鲁拉西酮剂量（40 - 120毫克/天）。主要安全终点是出现治疗中出现的不良事件（AE）、严重AE或因AE而停药的患者比例。次要终点包括代谢变量、锥体外系症状和静坐不能的测量指标，以及阳性和阴性症状量表（PANSS）、临床总体印象 - 严重程度（CGI - S）和精神分裂症卡尔加里抑郁量表（CDSS）。该研究于2010年8月至2011年11月进行。
在完成6周核心研究的198例患者中，149例（75.3%）进入延长期研究，148例接受了研究药物治疗。共有98例患者（65.8%）完成了为期6个月的延长期研究。鲁拉西酮40毫克、80毫克和120毫克分别是19例（12.8%）、65例（43.9%）和64例（43.2%）患者的每日平均剂量。鲁拉西酮每日总体平均（标准差）剂量为102.0毫克（77.1）。最常报告的AE为失眠（13例患者[8.8%]）、恶心（13例患者[8.8%]）、静坐不能（12例患者[8.1%]）和焦虑（9例患者[6.1%]）。共有16例患者（10.8%）至少有一项AE导致退出研究。与之前对鲁拉西酮的研究一致，在体重、血脂、血糖、胰岛素或催乳素方面未发现具有临床意义的不良变化信号。运动障碍评定量表未显示出有意义的变化。观察到19例患者（占入组患者的12.8%）出现治疗失败（定义为因临床反应不足、基础疾病加重或AE而导致的任何停药情况），治疗失败的中位时间为58天（95%置信区间22 - 86）。因任何原因导致的停药率为50/148（33.8%），停药的中位时间为62天（95%置信区间30 - 75）。从核心研究基线到延长期各访视时，PANSS总分平均值、CGI - S评分平均值和CDSS评分平均值持续下降，表明总体状况有所改善。
在这项为期6个月的开放标签延长期研究中，对于从多种抗精神病药物转换为使用鲁拉西酮治疗的精神分裂症或分裂情感性障碍门诊患者，鲁拉西酮治疗总体耐受性良好，且疗效指标持续改善。
