Global Development Team, Basel, Switzerland.
PD Neuroscience, Basel, Switzerland.
Biol Psychiatry. 2017 Jul 1;82(1):8-16. doi: 10.1016/j.biopsych.2016.11.014. Epub 2016 Dec 15.
There is currently no standard of care for treatment of negative symptoms of schizophrenia, although some previous results with glutamatergic agonists have been promising.
Three (SunLyte [WN25308], DayLyte [WN25309], and FlashLyte [NN25310]) phase III, multicenter, randomized, 24-week, double-blind, parallel-group, placebo-controlled studies evaluated the efficacy and safety of adjunctive bitopertin in stable patients with persistent predominant negative symptoms of schizophrenia treated with antipsychotics. SunLyte met the prespecified criteria for lack of efficacy and was declared futile. Key inclusion criteria were age ≥18 years, DSM-IV-TR diagnosis of schizophrenia, score ≥40 on the sum of the 14 Positive and Negative Syndrome Scale negative symptoms and disorganized thought factors, unaltered antipsychotic treatment, and clinical stability. Following a 4-week prospective stabilization period, patients were randomly assigned 1:1:1 to bitopertin (5 mg and 10 mg [DayLyte] and 10 mg and 20 mg [FlashLyte]) or placebo once daily for 24 weeks. The primary efficacy end point was mean change from baseline in Positive and Negative Syndrome Scale negative symptom factor score at week 24.
The intent-to-treat population in DayLyte and FlashLyte included 605 and 594 patients, respectively. At week 24, mean change from baseline showed improvement in all treatment arms but no statistically significant separation from placebo in Positive and Negative Syndrome Scale negative symptom factor score and all other end points. Bitopertin was well tolerated.
These studies provide no evidence for superior efficacy of adjunctive bitopertin in any of the doses tested over placebo in patients with persistent predominant negative symptoms of schizophrenia.
目前尚无治疗精神分裂症阴性症状的标准治疗方法，尽管以前使用谷氨酸能激动剂的一些结果很有希望。
三项（SunLyte [WN25308]、DayLyte [WN25309]和 FlashLyte [NN25310]） 三期、多中心、随机、24 周、双盲、平行组、安慰剂对照研究评估了辅助双哌替啶治疗稳定期精神分裂症患者持续主要阴性症状的疗效和安全性，这些患者正在接受抗精神病药物治疗。SunLyte 未达到预先设定的疗效标准，被宣布无效。主要纳入标准为年龄≥18 岁，DSM-IV-TR 诊断为精神分裂症，阳性和阴性综合征量表阴性症状和思维紊乱因子总分≥40 分，未改变的抗精神病药物治疗和临床稳定。经过 4 周的前瞻性稳定期后，患者以 1:1:1 的比例随机分配至双哌替啶（5 mg 和 10 mg [DayLyte]和 10 mg 和 20 mg [FlashLyte]）或安慰剂，每天一次，持续 24 周。主要疗效终点为第 24 周时阳性和阴性综合征量表阴性症状因子评分的基线变化平均值。
DayLyte 和 FlashLyte 的意向治疗人群分别包括 605 例和 594 例患者。第 24 周时，与基线相比，所有治疗组的平均变化均有所改善，但阳性和阴性综合征量表阴性症状因子评分和所有其他终点均与安慰剂无统计学差异。双哌替啶耐受性良好。
这些研究没有提供证据表明，在持续存在的精神分裂症主要阴性症状患者中，任何剂量的辅助双哌替啶与安慰剂相比，在任何方面都具有更好的疗效。
