Department of Psychiatry, Comprehensive Center for Depression, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9119
J Clin Psychiatry. 2013 Aug;74(8):802-9. doi: 10.4088/JCP.13m08360.
Evaluate the efficacy and safety of lisdexamfetamine dimesylate augmentation for major depressive disorder (MDD) in escitalopram nonremitters.
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.
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).
Lisdexamfetamine dimesylate augmentation reduced depressive symptoms in participants with inadequate escitalopram response.
ClinicalTrials.gov identifier: NCT00905424.
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。
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。
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）。
lisdexamfetamine dimesylate 增效治疗可减轻艾司西酞普兰应答不足患者的抑郁症状。
ClinicalTrials.gov 标识符：NCT00905424。
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