Alderman Jeffrey, Wolkow Robert, Fogel Ilan M
Pfizer Inc, New York, New York 10017, USA.
J Child Adolesc Psychopharmacol. 2006 Feb-Apr;16(1-2):117-29. doi: 10.1089/cap.2006.16.117.
The aim of this study was to evaluate the long-term pharmacokinetics, safety, and efficacy of sertraline in children and adolescents with obsessive-compulsive disorder (OCD) or major depressive disorder (MDD).
After 42-day initial treatment and 9-day withdrawal phases, children (6-12 years, n = 16) and adolescents (13-18 years, n = 27) entered a 24-week open-label phase, with sertraline titrated to 200 mg/day. Blood samples for plasma sertraline and N-desmethylsertraline levels were taken at the beginning of the 24-week phase and at weeks 1, 4, 8, 12, and 24. Efficacy and safety data were also collected.
Mean maximum daily dose at endpoint was 157 +/- 49 mg. For female and male children, mean sertraline/N-desmethylsertraline concentrations normalized to a 200-mg dose were 85.0/160 ng/mL (n = 8) and 79.3/134 ng/mL (n = 8), respectively, and for female and male adolescents, 70.5/109 ng/mL (n = 16) and 76.3/120 ng/mL (n = 8). No significant age or gender effects or age-by-gender interactions were observed in sertraline values. Mean sertraline plasma concentrations normalized for dose and body weight did not differ significantly by age or gender. Three (3) patients (7%) discontinued owing to adverse events. In patients with OCD (n = 10), improvements were observed in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) (p = 0.029) and National Institute of Mental Health (NIMH) Global Obsessive Compulsive Scale (OCS) (p = 0.01). In MDD patients (n = 32), Clinical Global Impression (CGI) Severity (p = 0.002) and Improvement (p = 0.011) improved.
Long-term treatment of MDD and OCD with sertraline up to 200 mg/day in children and adolescents results in dose-normalized plasma concentrations comparable to those seen in adults. Sertraline was generally well tolerated, and patients demonstrated clinical improvement over 24 weeks of treatment.
本研究旨在评估舍曲林在患有强迫症（OCD）或重度抑郁症（MDD）的儿童和青少年中的长期药代动力学、安全性及疗效。
在经过42天的初始治疗和9天的撤药期后，儿童（6至12岁，n = 16）和青少年（13至18岁，n = 27）进入为期24周的开放标签期，舍曲林滴定至200毫克/天。在24周阶段开始时以及第1、4、8、12和24周采集血样以检测血浆舍曲林和N-去甲基舍曲林水平。同时收集疗效和安全性数据。
终点时的平均最大日剂量为157±49毫克。对于女童和男童，按200毫克剂量归一化后的平均舍曲林/N-去甲基舍曲林浓度分别为85.0/160纳克/毫升（n = 8）和79.3/134纳克/毫升（n = 8），对于女青少年和男青少年，分别为70.5/109纳克/毫升（n = 16）和76.3/120纳克/毫升（n = 8）。在舍曲林值方面未观察到显著的年龄或性别效应以及年龄与性别的交互作用。按剂量和体重归一化后的平均舍曲林血浆浓度在年龄或性别上无显著差异。3名（7%）患者因不良事件停药。在患有OCD的患者（n = 10）中，儿童耶鲁-布朗强迫症量表（CY-BOCS）（p = 0.029）和美国国立精神卫生研究所（NIMH）全球强迫症量表（OCS）（p = 0.01）有所改善。在患有MDD的患者（n = 32）中，临床总体印象（CGI）严重程度（p = 0.002）和改善情况（p = 0.011）有所改善。
在儿童和青少年中，使用舍曲林每日高达200毫克对MDD和OCD进行长期治疗，其剂量归一化后的血浆浓度与成人相当。舍曲林总体耐受性良好，患者在24周的治疗中显示出临床改善。
