From the Department of Psychiatry and Behavioral Sciences, New York Medical College, Valhalla, NY.
Biostatistics, Otsuka Pharmaceutical Development & Commercialization Inc, Princeton, NJ.
J Clin Psychopharmacol. 2019 Nov/Dec;39(6):597-603. doi: 10.1097/JCP.0000000000001113.
Managing agitation and hostility represents a significant treatment challenge in schizophrenia. The aim of this analysis was to evaluate the short- and long-term efficacy of brexpiprazole for reducing agitation and hostility in schizophrenia.
This was a post hoc analysis of data from two 6-week, randomized, double-blind, placebo-controlled studies (ClinicalTrials.gov identifiers, NCT01396421 and NCT01393613) and a 52-week, open-label, extension study (NCT01397786). In the short-term studies, 1094 patients received placebo, 2 mg/d of brexpiprazole, or 4 mg/d of brexpiprazole; 346 brexpiprazole-treated patients rolled over into the long-term study and received 1 to 4 mg/d of brexpiprazole. Agitation was assessed using the Positive and Negative Syndrome Scale (PANSS) Excited Component (EC), and hostility was assessed using the PANSS hostility item (P7).
Brexpiprazole improved PANSS-EC score over 6 weeks, with least squares mean differences versus placebo of -0.69 (95% confidence limits, -1.28, -0.11) for 2 mg/d (P = 0.020) and -1.11 (-1.70, -0.53) for 4 mg/d (P = 0.0002). In the subgroup with hostility at baseline (P7 score ≥3; 50.8% of the randomized sample), least squares mean differences versus placebo at week 6 on the PANSS-EC were -0.63 (-1.54, 0.28) for 2 mg/d (P = 0.18) and -1.03 (-1.92, -0.14) for 4 mg/d (P = 0.024), and on P7 (adjusted for positive symptoms) were -0.27 (-0.53, -0.01) for 2 mg/d (P = 0.038) and -0.34 (-0.59, -0.09) for 4 mg/d (P = 0.0080). The improvements were maintained over 58 weeks. Adverse events were generally comparable between treatment groups over 6 weeks; the incidence of akathisia among patients with hostility was 5.9% with placebo, 5.2% with 2 mg/d, and 8.6% with 4 mg/d.
Brexpiprazole has the potential to be an efficacious and well-tolerated treatment for agitation and hostility among patients with schizophrenia.
管理精神分裂症患者的激越和敌意是一项重大治疗挑战。本分析的目的是评估 Brexpiprazole 降低精神分裂症患者激越和敌意的短期和长期疗效。
这是两项 6 周、随机、双盲、安慰剂对照研究（ClinicalTrials.gov 标识符：NCT01396421 和 NCT01393613）和一项 52 周、开放标签、扩展研究（NCT01397786）的事后分析。在短期研究中，1094 名患者接受安慰剂、2mg/d Brexpiprazole 或 4mg/d Brexpiprazole；346 名 Brexpiprazole 治疗的患者继续进入长期研究，接受 1 至 4mg/d Brexpiprazole。使用阳性和阴性综合征量表（PANSS）兴奋成分（EC）评估激越，使用 PANSS 敌意项目（P7）评估敌意。
Brexpiprazole 在 6 周内改善了 PANSS-EC 评分，与安慰剂相比，2mg/d 的最小二乘均值差异为 -0.69（95%置信区间，-1.28，-0.11）（P=0.020），4mg/d 的差异为 -1.11（-1.70，-0.53）（P=0.0002）。在基线时存在敌意的亚组（P7 评分≥3；随机样本的 50.8%）中，与安慰剂相比，6 周时 PANSS-EC 的最小二乘均值差异在 2mg/d 时为 -0.63（-1.54，0.28）（P=0.18），在 4mg/d 时为 -1.03（-1.92，-0.14）（P=0.024），在 P7（针对阳性症状进行调整）时为 -0.27（-0.53，-0.01）（P=0.038），在 4mg/d 时为 -0.34（-0.59，-0.09）（P=0.0080）。这些改善在 58 周内得以维持。在 6 周内，各组之间的不良反应通常相当；有敌意的患者中静坐不能的发生率安慰剂组为 5.9%，2mg/d 组为 5.2%，4mg/d 组为 8.6%。
Brexpiprazole 有可能成为一种有效且耐受性良好的治疗精神分裂症患者激越和敌意的药物。
