Hirayasu Yoshio, Sato Shin-Ichi, Takahashi Hideaki, Iida Sayaka, Shuto Norifumi, Yoshida Seitaro, Funatogawa Takashi, Yamada Takahito, Higuchi Teruhiko
Department of Psychiatry, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
BMC Psychiatry. 2016 Mar 15;16:66. doi: 10.1186/s12888-016-0778-9.
Bitopertin, a glycine reuptake inhibitor, was investigated as a novel treatment for schizophrenia. We report all the results of a double-blind randomized study assessing safety and efficacy following 52-week adjunctive treatment with bitopertin in Japanese patients with schizophrenia.
This study enrolled Japanese outpatients with schizophrenia who met criteria for either "negative symptoms", i.e., patients with persistent, predominant negative symptoms of schizophrenia even after long-term treatment with antipsychotics or "sub-optimally controlled symptoms", i.e., patients with insufficiently improved symptoms of schizophrenia even after long-term treatment with antipsychotics, respectively. One hundred sixty-one patients were randomly assigned to receive 52-week treatments with bitopertin doses of 5, 10, or 20 mg/day at ratio of 1:5:5, where existing antipsychotics were concomitantly administered. Efficacy endpoints included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), and Personal and Social Performance (PSP). The purpose of the present study is primarily to evaluate the safety, and secondarily to investigate the clinical efficacy of bitopertin.
One hundred fourteen patients (71 %) completed 52-week treatment with bitopertin. Most of the adverse events were mild or moderate in their severity. The patients in the 20-mg group experienced more adverse events than the patients in the other two groups. Common dose-dependent adverse events were somnolence and insomnia associated with worsening schizophrenia. The blood hemoglobin levels gradually decreased from baseline in a dose-dependent manner, but there were no patients with the decrease below 10 g/dL that would have led to their discontinuation. All the efficacy endpoints gradually improved in all the treatment groups for both of the two symptoms, while there were no clear differences among the three dose groups.
Altogether, bitopertin was found to be generally safe and well-tolerated for the treatment of patients with schizophrenia. All three bitopertin treated groups showed improvements in all the efficacy endpoints for both of the two symptoms, i.e., "negative symptoms" and "sub-optimally controlled symptoms", throughout the duration of the study.
Japan Pharmaceutical Information Center, number JapicCTI-111627 (registered on September 20, 2011).
甘氨酸再摄取抑制剂比特麦汀被作为精神分裂症的一种新疗法进行研究。我们报告一项双盲随机研究的所有结果，该研究评估了比特麦汀对日本精神分裂症患者进行52周辅助治疗后的安全性和疗效。
本研究纳入符合“阴性症状”标准的日本精神分裂症门诊患者，即即使经过长期抗精神病药物治疗仍存在持续性、主要为阴性症状的患者，或符合“症状控制欠佳”标准的患者，即即使经过长期抗精神病药物治疗精神分裂症症状改善仍不充分的患者。161例患者按1:5:5的比例随机分配接受52周的比特麦汀治疗，剂量分别为5、10或20mg/天，同时继续服用现有的抗精神病药物。疗效终点包括阳性与阴性症状量表（PANSS）、临床总体印象量表（CGI）和个人与社会功能量表（PSP）。本研究的目的主要是评估安全性，并次要研究比特麦汀的临床疗效。
114例患者（71%）完成了52周的比特麦汀治疗。大多数不良事件的严重程度为轻度或中度。20mg组患者经历的不良事件比其他两组患者更多。常见的剂量依赖性不良事件是与精神分裂症病情恶化相关的嗜睡和失眠。血红蛋白水平从基线开始呈剂量依赖性逐渐下降，但没有患者的血红蛋白水平降至10g/dL以下而导致停药。对于两种症状，所有治疗组的所有疗效终点均逐渐改善，而三个剂量组之间没有明显差异。
总体而言，发现比特麦汀治疗精神分裂症患者一般安全且耐受性良好。在整个研究期间，三个比特麦汀治疗组在“阴性症状”和“症状控制欠佳”这两种症状的所有疗效终点上均有改善。
日本药品信息中心，编号JapicCTI - 111627（于2011年9月20日注册）。
