Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio, USA.
J Clin Psychiatry. 2010 Oct;71(10):1363-70. doi: 10.4088/JCP.09m05900gry. Epub 2010 Jul 27.
To evaluate the efficacy and safety of armodafinil, the longer-lasting isomer of modafinil, when used adjunctively in patients with bipolar depression.
In this 8-week, multicenter, randomized, double-blind, placebo-controlled study conducted between June 2007 and December 2008, patients who were experiencing a major depressive episode associated with bipolar I disorder (according to DSM-IV-TR criteria) despite treatment with lithium, olanzapine, or valproic acid were randomly assigned to adjunctive armodafinil 150 mg/d (n = 128) or placebo (n = 129) administered once daily in the morning. The primary outcome measure was change from baseline in the total 30-item Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C₃₀) score. Secondary outcomes included changes from baseline in scores on the Montgomery-Åsberg Depression Rating Scale, among other psychological symptom scales. Statistical analyses were performed using analysis of covariance (ANCOVA), with study drug and concurrent mood stabilizer treatment for bipolar disorder as factors and the corresponding baseline value as a covariate. A prespecified sensitivity analysis was done using analysis of variance (ANOVA) if a statistically significant treatment-by-baseline interaction was found. Tolerability was also assessed.
A significant baseline-by-treatment interaction in the total IDS-C₃₀ score (P = .08) was found. Patients administered adjunctive armodafinil showed greater improvement in depressive symptoms as seen in the greater mean ± SD change on the total IDS-C₃₀ score (-15.8 ± 11.57) compared with the placebo group (-12.8 ± 12.54) (ANOVA: P = .044; ANCOVA: P = .074). No differences between treatment groups were observed in secondary outcomes. Adverse events reported more frequently in patients receiving adjunctive armodafinil were headache, diarrhea, and insomnia. Armodafinil was not associated with an increased incidence and/or severity of suicidality, depression, or mania or with changes in metabolic profile measurements.
In this proof-of-concept study, adjunctive armodafinil 150 mg/d appeared to improve depressive symptoms according to some, but not all, measures and was generally well tolerated in patients with bipolar depression.
clinicaltrials.gov Identifier: NCT00481195.
评估阿莫达非尼（莫达非尼的长时异构体）作为辅助药物治疗双相抑郁的疗效和安全性。
这是一项为期 8 周、多中心、随机、双盲、安慰剂对照的研究，于 2007 年 6 月至 2008 年 12 月进行，纳入了正在接受锂盐、奥氮平或丙戊酸钠治疗但仍存在双相 I 型障碍相关重性抑郁发作的患者（根据 DSM-IV-TR 标准）。将患者随机分配至阿莫达非尼 150mg/d 组（n=128）或安慰剂组（n=129），每天早晨 1 次口服。主要终点是基于 30 项抑郁症状清单，临床医生评定版（IDS-C₃₀）总分的基线变化。次要终点包括蒙哥马利-Åsberg 抑郁评定量表（among other psychological symptom scales）等其他心理症状量表评分的基线变化。使用协方差分析（ANCOVA）进行统计分析，以研究药物和双相障碍的同时心境稳定剂治疗为因素，相应的基线值为协变量。如果发现治疗与基线之间存在统计学显著的交互作用，则进行方差分析（ANOVA）的预设敏感性分析。还评估了耐受性。
发现总 IDS-C₃₀ 评分的基线与治疗之间存在显著的交互作用（P=0.08）。接受辅助阿莫达非尼治疗的患者抑郁症状改善更为明显，总 IDS-C₃₀ 评分的平均变化值更大（-15.8 ± 11.57），而安慰剂组为（-12.8 ± 12.54）（方差分析：P=0.044；协方差分析：P=0.074）。两组在次要终点上无差异。接受辅助阿莫达非尼治疗的患者报告的不良事件更常见的是头痛、腹泻和失眠。阿莫达非尼与自杀意念、抑郁或躁狂的发生率和/或严重程度增加无关，也不会改变代谢指标。
在这项概念验证研究中，辅助阿莫达非尼 150mg/d 治疗似乎可以改善一些但不是所有的抑郁症状，并且在双相抑郁患者中通常具有良好的耐受性。
clinicaltrials.gov 标识符：NCT00481195。
