BACKGROUND:The efficacy, safety, and tolerability of lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy in adults with major depressive disorder (MDD) from two phase 3 studies are reported. METHODS:Across study 1 (placebo, n=201; LDX, n=201) and study 2 (placebo, n=213; LDX, n=211), most participants (placebo and LDX) in the safety analysis set were female (study 1: 66.2% and 64.2%; study 2: 67.1% and 66.8%); mean±SD ages were 41.8±12.04 with placebo and 42.2±12.32 with LDX in study 1 and 42.6±11.41 with placebo and 42.0±11.63 with LDX in study 2. Participants (18-65 y) had DSM-IV-TR-diagnosed MDD and lead-in baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total scores ≥24. Eight-week antidepressant lead-in phases prospectively assessed antidepressant response. Then, 8 weeks of randomized (1:1), double-blind treatment with dose-optimized LDX (20-70mg) or placebo in participants exhibiting inadequate antidepressant monotherapy responses (augmentation baseline MADRS total scores ≥18 and <50% MADRS total score reductions from lead-in baseline to augmentation baseline) was initiated. The primary endpoint was MADRS total score change from augmentation baseline to week 16. Safety and tolerability measures included the occurrence of treatment-emergent adverse events (TEAEs). RESULTS:Least squares mean (95% CI) treatment differences (LDX-placebo) for MADRS total score changes from augmentation baseline to week 16 were not statistically significant in study 1 (0.1 [-1.7, 2.0], P=0.883) or study 2 (-0.5 [-2.3, 1.3], P=0.583). The only TEAE reported by >5% of LDX participants at twice the placebo rate in both studies was dry mouth. LIMITATIONS:Limitations include the exclusion of participants with psychiatric comorbidities/active medical disorders, the inability to assess specific MDD symptom domains (eg, anhedonia, cognition) or subtypes, the use of telephone-based depression assessments, and the potential influence of placebo response. CONCLUSION:Contrary to expectations, LDX augmentation was not superior to placebo in reducing depressive symptoms in individuals with MDD exhibiting inadequate responses to antidepressant monotherapy.

译文

背景:从两项3期研究中报告了赖斯地非米他明二甲磺酸酯(LDX)增强抗抑郁药单一疗法在成人重度抑郁症(MDD)中的疗效,安全性和耐受性。
方法:在研究1(安慰剂,n = 201; LDX,n = 201)和研究2(安慰剂,n = 213; LDX,n = 211)中,安全性分析集中的大多数参与者(安慰剂和LDX)是女性(研究1:66.2%和64.2%;研究2:67.1%和66.8%);在研究1中,安慰剂组的平均±SD年龄为41.8±12.04,在LDX中为42.2±12.32,在安慰剂组中为42.6±11.41,在LDX中为42.0±11.63。研究对象(18-65岁)的DSM-IV-TR诊断为MDD和导入的基线蒙哥马利-奥斯伯格抑郁量表(MADRS)总分≥24。八周的抗抑郁药导入期前瞻性评估了抗抑郁药的反应。然后,对表现出抗抑郁单一疗法反应不足的参与者(增强基线MADRS总分≥18,MADRS总分<50%)进行随机化(1:1),剂量优化的LDX(20-70mg)或安慰剂双盲治疗8周从导入基准减少到增强基准)。主要终点是从增强基线到第16周的MADRS总得分变化。安全性和耐受性措施包括治疗紧急不良事件(TEAE)的发生。
结果:在研究1(0.1 [-1.7,2.0],P = 0.883)或研究中,从增强基线到第16周的MADRS总评分变化的最小二乘均值(95%CI)治疗差异(LDX-安慰剂)没有统计学意义。 2(-0.5 [-2.3,1.3],P = 0.583)。在两项研究中,超过5%的LDX参与者报告的安慰剂发生率是5%的唯一TEAE是口干。
局限性:限制包括排除患有精神病合并症/活动性疾病,无法评估特定MDD症状域(例如,快感,认知)或亚型的参与者,使用基于电话的抑郁症评估以及安慰剂反应的潜在影响。
结论:与预期相反,在MDD对抗抑郁单一疗法反应不足的个体中,LDX增强在减轻抑郁症状方面不优于安慰剂。

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