Emslie Graham J, Prakash Apurva, Zhang Qi, Pangallo Beth A, Bangs Mark E, March John S
1 Child and Adolescent Psychiatry Division, University of Texas Southwestern and Children's Medical Center , Dallas, Texas.
J Child Adolesc Psychopharmacol. 2014 May;24(4):170-9. doi: 10.1089/cap.2013.0096. Epub 2014 May 9.
The purpose of this study was to evaluate the efficacy and safety of duloxetine fixed dose in the treatment of children (7-11 years) and adolescents (12-17 years) with major depressive disorder (MDD).
Patients (n=463) in this 36 week study (10 week acute and 26 week extension treatment) received duloxetine 60 mg QD (n=108), duloxetine 30 mg QD (n=116), fluoxetine 20 mg QD (n=117, active control), or placebo (n=122). Measures included: Children's Depression Rating Scale-Revised (CDRS-R), treatment-emergent adverse events (TEAEs), and Columbia-Suicide Severity Rating Scale (C-SSRS).
Neither active drug (duloxetine or fluoxetine) separated significantly (p<0.05) from placebo on mean change from baseline to end-point (10 weeks) on the CDRS-R total score. Total TEAEs and discontinuation for AEs were significantly (p<0.05) higher only for the duloxetine 60 mg group versus the placebo group during acute treatment. No clinically significant electrocardiogram (ECG) or laboratory abnormalities were observed, and no completed suicides or deaths occurred during the study. A total of 7 (6.7%) duloxetine 60 mg, 6 (5.2%) duloxetine 30 mg, 9 (8.0%) fluoxetine, and 11 (9.4%) placebo patients had worsening of suicidal ideation from baseline during acute treatment. Of the patients with suicidal ideation at baseline, 13/16 (81%) duloxetine 60 mg, 16/17 (94%) duloxetine 30 mg, 11/16 (69%) fluoxetine, and 13/15 (87%) placebo had improvement in suicidal ideation at end-point during acute treatment. One fluoxetine, one placebo, and six duloxetine patients had treatment-emergent suicidal behavior during the 36 week study.
Trial results were inconclusive, as neither the investigational drug (duloxetine) nor the active control (fluoxetine) separated from placebo on the CDRS-R at 10 weeks. No new duloxetine safety signals were identified relative to those seen in adults. Clinical Trial Registry Number ( www.ClinicalTrials.gov ): NCT00849693.
本研究旨在评估度洛西汀固定剂量治疗儿童（7 - 11岁）和青少年（12 - 17岁）重度抑郁症（MDD）的疗效和安全性。
在这项为期36周的研究（10周急性治疗和26周延长期治疗）中，463例患者接受度洛西汀60mg每日一次（n = 108）、度洛西汀30mg每日一次（n = 116）、氟西汀20mg每日一次（n = 117，活性对照）或安慰剂（n = 122）治疗。测量指标包括：儿童抑郁评定量表修订版（CDRS - R）、治疗中出现的不良事件（TEAE）和哥伦比亚自杀严重程度评定量表（C - SSRS）。
在CDRS - R总分从基线到终点（10周）的平均变化方面，活性药物（度洛西汀或氟西汀）与安慰剂相比均未显著分离（p < 0.05）。在急性治疗期间，仅度洛西汀60mg组的总TEAE和因不良事件停药的比例显著高于安慰剂组（p < 0.05）。未观察到具有临床意义的心电图（ECG）或实验室异常，且研究期间未发生完全自杀或死亡事件。共有7例（6.7%）度洛西汀60mg组、6例（5.2%）度洛西汀30mg组、9例（8.0%）氟西汀组和11例（9.4%）安慰剂组患者在急性治疗期间自杀观念较基线恶化。在基线时有自杀观念的患者中，13/16（81%）度洛西汀60mg组、16/17（94%）度洛西汀30mg组、11/16（69%）氟西汀组和13/15（87%）安慰剂组患者在急性治疗终点时自杀观念有所改善。在36周研究期间，1例氟西汀组、1例安慰剂组和6例度洛西汀组患者出现治疗中出现的自杀行为。
试验结果尚无定论，因为在10周时，研究药物（度洛西汀）和活性对照（氟西汀）在CDRS - R上均未与安慰剂分离。相对于成人中观察到的情况，未发现度洛西汀新的安全信号。临床试验注册号（www.ClinicalTrials.gov）：NCT00849693。
