Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA.
Sunovion Pharmaceuticals, Inc., Marlborough, Massachusetts, and Fort Lee, New Jersey, USA.
J Child Adolesc Psychopharmacol. 2020 Dec;30(10):590-598. doi: 10.1089/cap.2020.0018. Epub 2020 May 8.
To evaluate the efficacy and safety of lurasidone in the treatment of children and adolescents with bipolar depression presenting with mixed (subsyndromal hypomanic) features. Patients, 10-17 years of age, with a Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5), diagnosis of bipolar I depression were randomized to 6 weeks of double-blind treatment with once-daily flexible doses of lurasidone 20-80 mg or placebo. The presence of mixed (subsyndromal hypomanic) features in this pediatric bipolar depression trial was defined as a Young Mania Rating Scale score of 5 or greater at study baseline. Key efficacy measures included change from baseline to week 6 in the Children's Depression Rating Scale-Revised (CDRS-R) score (primary endpoint) and Clinical Global Impressions-Bipolar Severity (CGI-BP-S) score, using a mixed model for repeated measures analysis. At baseline, subsyndromal hypomanic features were present in 54.2% of patients. Treatment with lurasidone (vs. placebo) was associated with significantly greater reductions in CDRS-R scores at week 6, independent of the presence (-21.5 vs. -15.9, < 0.01; effect size = 0.43) or absence (-20.5 vs. -14.9, < 0.01; = 0.44) of subsyndromal hypomanic features. Likewise, lurasidone (vs. placebo) was associated with significantly greater reductions in CGI-BP-S scores at week 6, independent of the presence (-1.6 vs. -1.1, < 0.001, = 0.51) or absence (-1.3 vs. -1.0, = 0.05; = 0.31) of these subsyndromal hypomanic features. Rates of protocol-defined treatment-emergent hypomania or mania were similar for lurasidone and placebo in patients with (lurasidone 8.2% vs. placebo 9.0%) or without subsyndromal hypomanic features (lurasidone 1.3% vs. placebo 3.7%). In this analysis of a randomized placebo-controlled trial, lurasidone was found to be efficacious in the treatment of child and adolescent patients with bipolar depression who presented with mixed (subsyndromal hypomanic) features. No differences in safety profile, including the risk of treatment-emergent mania, were observed in patients with or without subsyndromal hypomanic features in this study.
评估鲁拉西酮治疗伴有混合（亚综合征轻躁狂）特征的儿童和青少年双相情感障碍的疗效和安全性。 年龄在 10-17 岁之间的患者，符合精神障碍诊断与统计手册，第 5 版（DSM-5）双相 I 型抑郁的诊断，随机分为 6 周的双盲治疗，每日一次服用鲁拉西酮 20-80mg 或安慰剂。本项儿科双相抑郁试验中混合（亚综合征轻躁狂）特征的存在定义为研究基线时 Young Mania Rating Scale 评分≥5。主要疗效指标包括从基线到第 6 周时儿童抑郁评定量表修订版（CDRS-R）评分（主要终点）和临床总体印象-双相严重程度（CGI-BP-S）评分的变化，使用重复测量混合模型进行分析。 基线时，54.2%的患者存在亚综合征轻躁狂特征。与安慰剂相比，鲁拉西酮治疗与 CDRS-R 评分在第 6 周时的显著降低相关，与是否存在（-21.5 比-15.9， < 0.01；效应量 = 0.43）或不存在（-20.5 比-14.9， < 0.01； = 0.44）亚综合征轻躁狂特征无关。同样，与安慰剂相比，鲁拉西酮治疗与第 6 周 CGI-BP-S 评分的显著降低相关，与是否存在（-1.6 比-1.1， < 0.001， = 0.51）或不存在（-1.3 比-1.0， = 0.05； = 0.31）亚综合征轻躁狂特征无关。在伴有（鲁拉西酮 8.2%，安慰剂 9.0%）或不伴有亚综合征轻躁狂特征（鲁拉西酮 1.3%，安慰剂 3.7%）的患者中，鲁拉西酮和安慰剂的方案定义的治疗性轻躁狂或躁狂的发生率相似。在这项随机安慰剂对照试验的分析中，鲁拉西酮对伴有混合（亚综合征轻躁狂）特征的儿童和青少年双相情感障碍患者的治疗有效。在这项研究中，无论患者是否存在亚综合征轻躁狂特征，安全性特征（包括治疗性躁狂的风险）均无差异。
