Medical Division, Gedeon Richter Plc, Budapest, Hungary.
Medical Division, Gedeon Richter Plc, Budapest, Hungary.
Lancet. 2017 Mar 18;389(10074):1103-1113. doi: 10.1016/S0140-6736(17)30060-0. Epub 2017 Feb 7.
Although predominant negative symptoms of schizophrenia can be severe enough to cause persistent impairment, effective treatment options are lacking. We aimed to assess the new generation antipsychotic cariprazine in adult patients with predominant negative symptoms.
In this randomised, double-blind, phase 3b trial, we enrolled adults aged 18-65 years with long-term (>2 year), stable schizophrenia and predominant negative symptoms (>6 months) at 66 study centres (mainly hospitals and university clinics, with a small number of private practices) in 11 European countries. Patients were randomly assigned (1:1) by an interactive web response system to 26 weeks of monotherapy with fixed-dose oral cariprazine (3 mg, 4·5 mg [target dose], or 6 mg per day) or risperidone (3 mg, 4 mg [target dose], or 6 mg per day); previous medication was discontinued over 2 weeks. The primary outcome was change from baseline to week 26 or end of treatment on the Positive and Negative Syndrome Scale factor score for negative symptoms (PANSS-FSNS) analysed in a modified intention-to-treat population of patients who had follow-up assessments within 5 days after last receipt of study drugs with a mixed-effects model for repeated measures. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with EudraCT, number 2012-005485-36.
Between May 27, 2013, and Nov 17, 2014, 533 patients were screened and 461 (86%) patients were randomised to treatment (230 for cariprazine and 231 for risperidone); 460 were included in the safety population (one patient discontinued before study drug intake). 227 (99%) of 230 patients in the cariprazine group and 229 (99%) of 230 patients in the risperidone group were included in the modified intention-to-treat population (178 [77%] in each group completed 26 weeks of treatment). Mean daily doses were 4·2 mg (SD 0·6) for cariprazine and 3·8 mg (0·4) for risperidone. Treatment-emergent adverse events (eg, insomnia, akathisia, worsening of schizophrenia, headache, anxiety) were reported in 123 (54%) patients treated with cariprazine and 131 (57%) patients treated with risperidone. Use of cariprazine led to a greater least squares mean change in PANSS-FSNS from baseline to week 26 than did risperidone (-8·90 points for cariprazine vs -7·44 points for risperidone; least squares mean difference -1·46, 95% CI -2·39 to -0·53; p=0·0022; effect size 0·31). One patient in the risperidone group died of a cause regarded as unrelated to treatment.
Our results support the efficacy of cariprazine in the treatment of predominant negative symptoms of schizophrenia.
Gedeon Richter Plc.
尽管精神分裂症的主要阴性症状可能严重到足以导致持续的损害，但缺乏有效的治疗选择。我们旨在评估新型抗精神病药卡利拉嗪在以主要阴性症状为主的成年患者中的疗效。
在这项随机、双盲、3b 期试验中，我们招募了年龄在 18-65 岁之间的成年人，他们患有长期（>2 年）、稳定的精神分裂症和主要阴性症状（>6 个月），共 66 个研究中心（主要是医院和大学诊所，还有少数私人诊所）分布在 11 个欧洲国家。患者通过交互式网络应答系统以 1:1 的比例随机分配，接受为期 26 周的单药治疗，分别接受固定剂量的口服卡利拉嗪（3mg、4.5mg[目标剂量]或 6mg/天）或利培酮（3mg、4mg[目标剂量]或 6mg/天）；在 2 周内停止之前的药物治疗。主要终点是从基线到第 26 周或治疗结束时，用经过修改的意向治疗人群中，使用混合效应重复测量模型对 PANSS-FSNS 因子评分的变化，该人群的患者在最后一次接受研究药物后 5 天内有随访评估。所有接受至少一剂研究药物的患者均进行安全性评估。本研究在 EudraCT 上注册，编号为 2012-005485-36。
2013 年 5 月 27 日至 2014 年 11 月 17 日期间，共筛查了 533 名患者，其中 461 名（86%）患者接受了治疗（卡利拉嗪组 230 名，利培酮组 231 名）；460 名患者纳入安全性人群（1 名患者在服用研究药物前停药）。卡利拉嗪组 230 名患者中有 227 名（99%），利培酮组 230 名患者中有 229 名（99%）被纳入修改后的意向治疗人群（每组各有 178 名患者完成了 26 周的治疗）。卡利拉嗪的平均日剂量为 4.2mg（标准差 0.6），利培酮的平均日剂量为 3.8mg（0.4）。接受卡利拉嗪治疗的 123 名（54%）患者和接受利培酮治疗的 131 名（57%）患者报告了治疗出现的不良事件（如失眠、静坐不能、精神分裂症恶化、头痛、焦虑）。与利培酮相比，卡利拉嗪治疗后 PANSS-FSNS 从基线到第 26 周的最小二乘均数变化更大（卡利拉嗪组为-8.90 分，利培酮组为-7.44 分；最小二乘均数差值-1.46，95%CI-2.39 至-0.53；p=0.0022；效应大小 0.31）。利培酮组有 1 名患者因被认为与治疗无关的原因死亡。
我们的研究结果支持卡利拉嗪在治疗精神分裂症主要阴性症状方面的疗效。
Gedeon Richter Plc.
