DelBello Melissa P, Hochadel Thomas J, Portland Kimberly Blanchard, Azzaro Albert J, Katic Alain, Khan Arif, Emslie Graham
1 Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research, University of Cincinnati College of Medicine , Cincinnati, Ohio.
J Child Adolesc Psychopharmacol. 2014 Aug;24(6):311-7. doi: 10.1089/cap.2013.0138. Epub 2014 Jun 23.
A randomized, double-blind, placebo-controlled flexible-dose, parallel group trial was conducted at 26 clinical investigational sites in the United States to examine the safety and efficacy of the selegiline transdermal system (STS) (EMSAM®) in adolescents (ages 12-17 years) meeting American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for moderate to severe major depressive disorder (MDD) without psychotic features.
Adolescents (n=308) with moderate to severe MDD were randomized to either STS (n=152) or placebo (n=156). Two hundred and fifteen (69.8%) subjects completed the study and 17 (5.5%) reported discontinuation because of adverse events (AEs). The primary efficacy outcome measure was the mean change from baseline to end of study (week 12 last observation carried forward [LOCF]) in the Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary outcome measures included end-point Clinical Global Impressions - Severity (CGI-S) and Clinical Global Impressions - Improvement (CGI-I).
Patients on STS or placebo had a significant decline from baseline (p<0.001) on their CDRS-R total score with mean reductions±SD as follows: STS 21.4±16.6; placebo 21.5±16.5. Both groups had similar response rates (58.6% vs. 59.3%) defined as CGI-I of 1 or 2 at study end. However, these between-group efficacy findings were without statistical significance. The overall incidence of reported AEs was 62.5% for STS-treated patients and 57.7% for placebo-treated patients. Most commonly reported AEs in STS or placebo groups were application site reactions (STS=24.3%; placebo=21.8%), headache (STS=17.1%; placebo=16.7%), and nausea (STS=7.2%; placebo=7.7%). Treatment groups did not differ on any laboratory parameters, vital signs, or electrocardiogram (ECG) findings. No suspected hypertensive crises were reported in the trial.
These data demonstrated that the STS was safe and well tolerated in this adolescent sample. However, both STS-treated and placebo-treated subjects demonstrated a decline from baseline in depressive symptoms (CDRS-R total score) over the length of the study, without statistical superiority by either group.
在美国26个临床研究点进行了一项随机、双盲、安慰剂对照、剂量灵活的平行组试验，以检验司来吉兰透皮系统（STS，商品名：安泰坦®）对符合美国精神病学协会《精神疾病诊断与统计手册》第4版（DSM-IV）中无精神病性特征的中度至重度重度抑郁症（MDD）标准的青少年（12 - 17岁）的安全性和有效性。
将308名中度至重度MDD青少年随机分为STS组（n = 152）或安慰剂组（n = 156）。215名（69.8%）受试者完成了研究，17名（5.5%）因不良事件（AE）报告停药。主要疗效指标是儿童抑郁评定量表修订版（CDRS - R）总分从基线到研究结束（第12周，末次观察结转[LOCF]）的平均变化。次要指标包括终点临床总体印象 - 严重程度（CGI - S）和临床总体印象 - 改善情况（CGI - I）。
接受STS或安慰剂治疗的患者CDRS - R总分较基线均有显著下降（p < 0.001），平均降低值±标准差如下：STS组为21.4±16.6；安慰剂组为21.5±16.5。两组的缓解率相似（58.6%对59.3%），定义为研究结束时CGI - I评分为1或2。然而，这些组间疗效结果无统计学意义。STS治疗患者报告的AE总发生率为62.5%，安慰剂治疗患者为57.7%。STS组或安慰剂组最常报告的AE是用药部位反应（STS组 = 24.3%；安慰剂组 = 21.8%）、头痛（STS组 = 17.1%；安慰剂组 = 16.7%）和恶心（STS组 = 7.2%；安慰剂组 = 7.7%）。治疗组在任何实验室参数、生命体征或心电图（ECG）结果方面均无差异。试验中未报告疑似高血压危象。
这些数据表明，STS在该青少年样本中是安全且耐受性良好的。然而，在整个研究过程中，接受STS治疗和安慰剂治疗的受试者抑郁症状（CDRS - R总分）均较基线有所下降，两组均无统计学上的优势。
