Rabinowitz Jonathan, Staner Corinne, Saoud Jay, Weiser Mark, Kuchibhatla Ramana, Davidson Michael, Harvey Phillip D, Luthringer Remy
Bar Ilan University, Ramat Gan 590002, Israel.
PPRS, 4e Av. du Général de Gaulle, 68000 Colmar, Grand EST, France.
Schizophr Res. 2023 May;255:9-13. doi: 10.1016/j.schres.2023.03.028. Epub 2023 Mar 16.
Roluperidone has antagonist properties for 5-HT, sigma, α- and α-adrenergic receptors, but no dopaminergic binding affinities. In 2 randomized controlled trials (RCT), treatment improved negative symptoms of schizophrenia and social functioning among patients with moderate to severe negative symptoms. We report results of the protocol specified analysis of 2 open-label extension studies of 24 and 40 weeks investigating whether improvement of negative symptoms was sustained without significant adverse effects or worsening of psychosis. Following 12-week double-blind phase of both RCTs, patients were eligible to receive monotherapy roluperidone 32 mg/day or 64 mg/day for 24 weeks (trial 1) or 40 weeks (trial 2) in open-label extension study. Trial 1 included 244 patients of whom 142 entered 24-week open-label extension and trial 2 included 513 patients of whom 341 entered 40-week open-label extension. Trial 1 had PANSS negative factor score of Pentagonal Structure Model as primary outcome. Trial 2 had Marder Negative Symptoms Factor Score as primary outcome measure and Personal and Social Performance (PSP) Total score as secondary outcome. During open-label extensions, continued improvements in negative symptoms and on PSP were observed. Overall rate of symptomatic worsening requiring discontinuation of roluperidone and treatment with an antipsychotic was <10 %. Roluperidone was well tolerated with no meaningful changes in vital signs, laboratory values, weight gain, metabolic indices, or extrapyramidal symptoms. Results of 2 open-label extension trials support roluperidone as a treatment of negative symptoms and social functioning deficits in patients with moderate to severe negative symptoms of schizophrenia.
鲁拉西酮对5-羟色胺、西格玛、α和α-肾上腺素能受体具有拮抗特性，但没有多巴胺能结合亲和力。在2项随机对照试验（RCT）中，治疗改善了中度至重度阴性症状患者的精神分裂症阴性症状和社会功能。我们报告了2项分别为期24周和40周的开放标签扩展研究的方案指定分析结果，该研究调查了阴性症状的改善是否持续，且无明显不良反应或精神病症状恶化。在两项RCT的12周双盲阶段之后，患者有资格在开放标签扩展研究中接受32毫克/天或64毫克/天的鲁拉西酮单药治疗，为期24周（试验1）或40周（试验2）。试验1纳入了244名患者，其中142名进入了为期24周的开放标签扩展阶段；试验2纳入了513名患者，其中341名进入了为期40周的开放标签扩展阶段。试验1以五角结构模型的PANSS阴性因子评分作为主要结局。试验2以马德阴性症状因子评分作为主要结局指标，以个人和社会表现（PSP）总分作为次要结局指标。在开放标签扩展阶段，观察到阴性症状和PSP持续改善。因症状恶化需要停用鲁拉西酮并用抗精神病药物治疗的总体发生率<10%。鲁拉西酮耐受性良好，生命体征、实验室值、体重增加、代谢指标或锥体外系症状均无有意义的变化。两项开放标签扩展试验的结果支持鲁拉西酮作为治疗精神分裂症中度至重度阴性症状患者的阴性症状和社会功能缺陷的药物。
