AbbVie, Irvine, California, USA.
AbbVie, North Chicago, Illinois, USA.
J Child Adolesc Psychopharmacol. 2024 Jun;34(5):241-250. doi: 10.1089/cap.2023.0080. Epub 2024 May 3.
Major depressive disorder (MDD) presents a significant psychosocial burden, and there is an unmet need for additional treatment options in pediatric patients. Here, we report the results of two phase 3 multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group studies evaluating the efficacy and safety of levomilnacipran extended release in children and adolescents with MDD. In the first study, LVM-MD-11, patients aged 12-17 years received daily doses of levomilnacipran 40 mg ( = 134), levomilnacipran 80 mg ( = 138), fluoxetine 20 mg ( = 134), or placebo ( = 141). In the second study, LVM-MD-14, patients aged 7-17 years received levomilnacipran 40 to 80 mg ( = 166), fluoxetine 20 mg ( = 166), or placebo ( = 160) daily. Primary and secondary efficacy endpoints were changes in Children's Depression Rating Scale-Revised (CDRS-R) total score and Clinical Global Impressions-Severity (CGI-S) score, respectively. In LVM-MD-11, there were no significant differences in change in CDRS-R total score between patients treated daily with placebo (least squares mean [LSM] change in CDRS-R total score -22.9) versus levomilnacipran 40 mg (-23.3; = 0.8035) or 80 mg (-22.6; = 0.8681). Similarly, in LVM-MD-14, there were no significant differences in LSM change in CDRS-R total score with placebo (-21.3) versus levomilnacipran 40 to 80 mg daily (-23.0; = 0.2215). There were also no significant differences between the fluoxetine and placebo groups in either study for changes in CDRS-R total score. Changes in CGI-S score were not significant between placebo and levomilnacipran 40 to 80 mg daily or between placebo and fluoxetine. Levomilnacipran was generally well tolerated. The high placebo response in this study prevented the detection of an effect of levomilnacipran in children and adolescents. Clinical Trial Registration numbers: NCT02431806 and NCT03569475.
重度抑郁症（MDD）会带来严重的社会心理负担，儿科患者需要额外的治疗选择。在这里，我们报告了两项 3 期、多中心、随机、双盲、安慰剂和活性对照、平行组研究的结果，这些研究评估了左米那普仑在儿童和青少年 MDD 中的疗效和安全性。在第一项研究 LVM-MD-11 中，年龄在 12-17 岁的患者每天接受左米那普仑 40mg（ = 134）、左米那普仑 80mg（ = 138）、氟西汀 20mg（ = 134）或安慰剂（ = 141）治疗。在第二项研究 LVM-MD-14 中，年龄在 7-17 岁的患者每天接受左米那普仑 40 至 80mg（ = 166）、氟西汀 20mg（ = 166）或安慰剂（ = 160）治疗。主要和次要疗效终点分别是儿童抑郁评定量表修订版（CDRS-R）总分和临床总体印象严重程度（CGI-S）评分的变化。在 LVM-MD-11 中，接受安慰剂（LSMSCDRS-R 总分变化-22.9）与左米那普仑 40mg（-23.3； = 0.8035）或 80mg（-22.6； = 0.8681）治疗的患者之间，CDRS-R 总分的变化无显著差异。同样，在 LVM-MD-14 中，接受安慰剂（-21.3）与左米那普仑 40 至 80mg 每日治疗（-23.0； = 0.2215）的患者之间，CDRS-R 总分的 LSMS 变化也无显著差异。在这两项研究中，氟西汀组与安慰剂组之间，CDRS-R 总分的变化也无显著差异。CGI-S 评分的变化在安慰剂和左米那普仑 40 至 80mg 每日治疗之间以及安慰剂和氟西汀之间均无显著差异。左米那普仑通常具有良好的耐受性。本研究中较高的安慰剂反应阻止了左米那普仑在儿童和青少年中的疗效检测。临床试验注册号：NCT02431806 和 NCT03569475。
