一项关于左乙拉西坦二甲磺酸盐作为增效治疗在使用依他普仑治疗后仍有残留症状的成人重性抑郁障碍患者中的疗效和安全性的随机对照试验。

A randomized controlled trial of the efficacy and safety of lisdexamfetamine dimesylate as augmentation therapy in adults with residual symptoms of major depressive disorder after treatment with escitalopram.

机构信息

Department of Psychiatry, Comprehensive Center for Depression, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9119

出版信息

J Clin Psychiatry. 2013 Aug;74(8):802-9. doi: 10.4088/JCP.13m08360.

DOI:10.4088/JCP.13m08360

PMID:24021497

Abstract

OBJECTIVE

Evaluate the efficacy and safety of lisdexamfetamine dimesylate augmentation for major depressive disorder (MDD) in escitalopram nonremitters.

METHOD

In this proof-of-concept study (conducted from July 2009-August 2010) with a prespecified critical α = .10, adults with nonpsychotic MDD (DSM-IV-TR criteria) and residual depressive symptoms (17-item Hamilton Depression Rating Scale score ≥ 4) after 8 weeks of open-label escitalopram were randomized to 6 weeks of lisdexamfetamine dimesylate (20-50 mg/d) or placebo augmentation. The primary endpoint, Montgomery-Asberg Depression Rating Scale (MADRS) total score change in escitalopram nonremitters (MADRS total score > 10) from week 8 (augmentation baseline) to week 14/end of study, was assessed using analysis of covariance, with last observation carried forward.

RESULTS

For nonremitters (placebo, n = 64; lisdexamfetamine dimesylate, n = 65), the least squares (LS) mean (90% CI) treatment difference for MADRS total score reduction at week 14/end of study (-2.3 [-4.5 to -0.1]; P = .0902) met the prespecified criterion for lisdexamfetamine dimesylate superiority (adjusted effect size, -0.3); the number needed to treat for MADRS remission (MADRS total score ≤ 10) was 6.7. The LS mean treatment difference in remitters was not statistically significant (1.2 [-1.6 to 4.0]; P = .4726). Among randomized participants, 49.4% (42/85) receiving placebo and 60.2% (53/88) receiving lisdexamfetamine dimesylate had ≥ 1 treatment-emergent adverse event, the most frequent with lisdexamfetamine dimesylate being dry mouth and headache (both 11.4%). Mean (SD) vital sign and electrocardiogram changes (placebo vs lisdexamfetamine dimesylate) were 0.5 (8.98) versus 2.3 (9.04) mm Hg (systolic blood pressure), -1.0 (7.19) versus 0.9 (6.61) mm Hg (diastolic blood pressure), -0.4 (7.39) versus 4.8 (8.64) beats per minute (heart rate), and -1.6 (11.23) versus -4.9 (11.84) milliseconds (Fridericia-adjusted QTc).

CONCLUSIONS

Lisdexamfetamine dimesylate augmentation reduced depressive symptoms in participants with inadequate escitalopram response.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT00905424.

摘要

目的

评估右苯丙胺二甲硫酸盐（lisdexamfetamine dimesylate）对艾司西酞普兰治疗无应答的重性抑郁障碍（MDD）患者的疗效和安全性。

方法

这是一项概念验证研究（于 2009 年 7 月至 2010 年 8 月进行），预先设定了关键的 α 值为.10，符合 DSM-IV-TR 标准的非精神病性 MDD （重性抑郁障碍）成年患者在接受 8 周艾司西酞普兰开放标签治疗后仍存在残留的抑郁症状（汉密尔顿抑郁量表 17 项评分[HAMD-17]≥4），被随机分为 lisdexamfetamine dimesylate（20-50mg/d）或安慰剂加用 6 周。主要终点是从第 8 周（增效期基线）到第 14 周/研究结束时，艾司西酞普兰无应答者（MADRS 总分＞10）的 Montgomery-Asberg 抑郁评定量表（MADRS）总分变化，采用协方差分析，观察值连续。

结果

对于无应答者（安慰剂组 n=64；lisdexamfetamine dimesylate 组 n=65），MADRS 总分在第 14 周/研究结束时的最小二乘（LS）均值（90%CI）治疗差异（-2.3[-4.5 至-0.1]；P=.0902）达到了 lisdexamfetamine dimesylate 优越性的预设标准（调整后的效应大小为-0.3）；达到 MADRS 缓解（MADRS 总分≤10）的需要治疗人数为 6.7。应答者的 LS 均值治疗差异无统计学意义（1.2[-1.6 至 4.0]；P=.4726）。在随机分组的参与者中，49.4%（42/85）接受安慰剂和 60.2%（53/88）接受 lisdexamfetamine dimesylate 的患者有≥1 次治疗出现的不良事件，最常见的是 lisdexamfetamine dimesylate 导致的口干和头痛（均为 11.4%）。（安慰剂 vs lisdexamfetamine dimesylate）的平均（SD）生命体征和心电图变化分别为 2.3mmHg（9.04）比 0.5mmHg（8.98）（收缩压），0.9mmHg（6.61）比 1.0mmHg（7.19）（舒张压），4.8 次/分钟（8.64）比 0.4 次/分钟（7.39）（心率）和-4.9ms（11.84）比-1.6ms（11.23）（Fridericia 校正 QTc）。