鲁拉西酮治疗伴有混合（亚综合征性轻躁狂）特征的双相抑郁：一项随机安慰剂对照试验的事后分析
Lurasidone in the treatment of bipolar depression with mixed (subsyndromal hypomanic) features: post hoc analysis of a randomized placebo-controlled trial.
作者信息
McIntyre Roger S, Cucchiaro Josephine, Pikalov Andrei, Kroger Hans, Loebel Antony
机构信息
University of Toronto, Departments of Psychiatry and Pharmacology, Mood Disorders Psychopharmacology Unit, 399 Bathurst St, MP 9-325, Toronto, ON, Canada M5T 2S8
出版信息
J Clin Psychiatry. 2015 Apr;76(4):398-405. doi: 10.4088/JCP.14m09410.
OBJECTIVE
Mixed (subsyndromal hypomanic) features are prevalent in patients with bipolar depression and are associated with more severe and complex illness, including increased risk for suicide attempts, higher switch to mania during antidepressant therapy, and a higher rate of recurrence. The aim of this post hoc analysis was to evaluate the efficacy and safety of lurasidone in the treatment of patients with bipolar depression presenting with mixed features.
METHOD
Patients with a DSM-IV-TR diagnosis of major depressive episode associated with bipolar I disorder, with or without rapid cycling, and with a Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20 and a Young Mania Rating Scale (YMRS) score ≤ 12 were randomly assigned to 6 weeks of double-blind, once-daily treatment with lurasidone 20-60 mg, lurasidone 80-120 mg, or placebo. The presence of mixed features was defined as a YMRS score ≥ 4 at study baseline. Efficacy analyses included change in MADRS total score from baseline to week 6 (the primary outcome in the original study, conducted between April 2009 and February 2012).
RESULTS
At baseline, mixed features were present in 56% of patients (lurasidone, n = 182/323; placebo, n = 90/162). Treatment with lurasidone (vs placebo) was associated with significantly greater reductions in MADRS scores in the mixed features group (-15.7 vs -10.9; P = .001; week 6; mixed model for repeated measures [MMRM]; effect size, 0.48) and in the group without mixed features (-15.2 vs -10.8; P = .002; week 6; MMRM; effect size, 0.48). Rates of protocol-defined treatment-emergent hypomania or mania were similar for patients with mixed features (lurasidone, 2.2%; placebo, 3.2%) and without mixed features (lurasidone, 3.4%; placebo, 0.0%).
CONCLUSIONS
Lurasidone was found in this post hoc analysis to be efficacious in the treatment of patients with bipolar depression who present with mixed features (assessed cross-sectionally at study baseline). No increased risk of treatment-emergent mania was observed in either group.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT00868699.
目的
混合（亚综合征性轻躁狂）特征在双相抑郁患者中普遍存在，且与更严重和复杂的病情相关，包括自杀未遂风险增加、抗抑郁治疗期间转为躁狂的几率更高以及复发率更高。这项事后分析的目的是评估鲁拉西酮治疗具有混合特征的双相抑郁患者的疗效和安全性。
方法
根据《精神疾病诊断与统计手册第四版修订版》（DSM-IV-TR）诊断为与双相I型障碍相关的重度抑郁发作的患者，无论是否有快速循环，蒙哥马利-阿斯伯格抑郁评定量表（MADRS）评分≥20且杨氏躁狂评定量表（YMRS）评分≤12，被随机分配接受为期6周的双盲治疗，每日一次，分别服用20 - 60mg鲁拉西酮、80 - 120mg鲁拉西酮或安慰剂。混合特征的存在定义为研究基线时YMRS评分≥4。疗效分析包括从基线到第6周MADRS总分的变化（这是2009年4月至2012年2月进行的原始研究的主要结局）。
结果
在基线时，56%的患者存在混合特征（鲁拉西酮组，n = 182/323；安慰剂组，n = 90/162）。在有混合特征的组中，鲁拉西酮治疗（与安慰剂相比）与MADRS评分显著更大幅度的降低相关（-15.7对-10.9；P = 0.001；第6周；重复测量混合模型[MMRM]；效应大小，0.48），在无混合特征的组中也是如此（-15.2对-10.8；P = 0.002；第6周；MMRM；效应大小，0.48）。有混合特征的患者（鲁拉西酮组为2.2%，安慰剂组为3.2%）和无混合特征的患者（鲁拉西酮组为3.4%，安慰剂组为0.0%）中，符合方案定义的治疗中出现的轻躁狂或躁狂发生率相似。
结论
在这项事后分析中发现，鲁拉西酮对具有混合特征（在研究基线时进行横断面评估）的双相抑郁患者有效。两组均未观察到治疗中出现躁狂的风险增加。
试验注册
ClinicalTrials.gov标识符：NCT00868699。
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