Emslie Graham J, Wells Thomas G, Prakash Apurva, Zhang Qi, Pangallo Beth A, Bangs Mark E, March John S
1 Department of Psychiatry, University of Texas Southwestern and Children's Medical Center , Dallas, Texas.
J Child Adolesc Psychopharmacol. 2015 May;25(4):293-305. doi: 10.1089/cap.2014.0076.
To assess acute and longer-term safety of duloxetine in the treatment of children and adolescents with major depressive disorder (MDD), a pooled analysis of data from two completed randomized, double-blind, multicenter, phase 3, placebo- and active-controlled trials was undertaken. In these studies, neither duloxetine (investigational drug) nor fluoxetine (active control) demonstrated a statistically significant improvement compared with placebo on the primary efficacy measure.
Patients ages 7-17 years with MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) received duloxetine (n=341), fluoxetine (n=234), or placebo (n=225) for 10 week acute and 26 week extended (duloxetine or fluoxetine only) treatments. Safety measures included treatment-emergent adverse events (TEAEs), the Columbia-Suicide Severity Rating Scale, vital signs, electrocardiograms, laboratory samples, and growth (height and weight) assessments.
Significantly more patients discontinued because of adverse events during duloxetine (8.2%) treatment than during placebo (3.1%) treatment (p≤0.05). TEAEs in >10% of duloxetine-treated patients were headache and nausea. No completed suicides or deaths occurred. During acute treatment, 6.6% of duloxetine-, 8.0% of fluoxetine-, and 8.2% of placebo-treated patients had worsening suicidal ideation from baseline. Among patients initially randomized to duloxetine or fluoxetine who had suicidal ideation at study baseline, 81% of duloxetine- and 77% of fluoxetine-treated patients had improvements in suicidal ideation at end-point in the 36-week studies. Suicidal behavior occurred in two fluoxetine-treated patients and one placebo-treated patient during acute treatment, and in seven duloxetine-treated patients and one fluoxetine-treated patient during extended treatment. Duloxetine-treated patients had a mean pulse increase of ∼3 beats per minute, and mean blood pressure (both systolic and diastolic) increases of <2.0 mm Hg at week 36. Weight decrease (≥3.5%) during acute treatment occurred with statistically (p≤0.05) greater frequency for both the duloxetine (11.4%) and fluoxetine (11.5%) groups versus the placebo (5.5%) group; however, mean weight increase occurred for both duloxetine and fluoxetine groups during extended treatment.
Results from this pooled analysis of two studies were consistent with the known safety and tolerability profile of duloxetine. Clinical Trial Registry Numbers: NCT00849901 and NCT00849693.
为评估度洛西汀治疗儿童和青少年重度抑郁症（MDD）的急性和长期安全性，对两项已完成的随机、双盲、多中心、3期、安慰剂对照和活性药物对照试验的数据进行了汇总分析。在这些研究中，与安慰剂相比，度洛西汀（研究药物）和氟西汀（活性对照药物）在主要疗效指标上均未显示出具有统计学意义的改善。
年龄在7至17岁、符合《精神疾病诊断与统计手册》第4版，修订版（DSM-IV-TR）中MDD定义的患者接受度洛西汀（n = 341）、氟西汀（n = 234）或安慰剂（n = 225）治疗，为期10周的急性治疗和26周的延长治疗（仅度洛西汀或氟西汀）。安全指标包括治疗中出现的不良事件（TEAE）、哥伦比亚自杀严重程度评定量表、生命体征、心电图、实验室样本以及生长（身高和体重）评估。
因不良事件而停药的度洛西汀治疗组患者（8.2%）显著多于安慰剂治疗组患者（3.1%）（p≤0.05）。在接受度洛西汀治疗的患者中，发生率超过10%的TEAE为头痛和恶心。未发生完全自杀或死亡事件。在急性治疗期间，度洛西汀治疗组中有6.6%的患者、氟西汀治疗组中有8.0%的患者以及安慰剂治疗组中有8.2%的患者自杀观念较基线恶化。在研究基线时有自杀观念且最初随机分配到度洛西汀或氟西汀治疗组的患者中，在36周研究的终点时，度洛西汀治疗组中有81%的患者以及氟西汀治疗组中有77%的患者自杀观念得到改善。在急性治疗期间，两名接受氟西汀治疗的患者和一名接受安慰剂治疗的患者出现了自杀行为，在延长治疗期间，七名接受度洛西汀治疗的患者和一名接受氟西汀治疗的患者出现了自杀行为。在第36周时，接受度洛西汀治疗的患者平均脉搏每分钟增加约3次，平均血压（收缩压和舒张压）升高均<2.0 mmHg。在急性治疗期间，度洛西汀组（11.4%）和氟西汀组（11.5%）体重下降（≥3.5%）的发生率在统计学上（p≤0.05）显著高于安慰剂组（5.5%）；然而，在延长治疗期间，度洛西汀组和氟西汀组患者的体重均出现了增加。
两项研究汇总分析的结果与度洛西汀已知的安全性和耐受性特征一致。临床试验注册号：NCT00849901和NCT00849693。
