Montoya Alonso, Hervas Amaia, Cardo Esther, Artigas Josep, Mardomingo María J, Alda José A, Gastaminza Xavier, García-Polavieja María J, Gilaberte Inmaculada, Escobar Rodrigo
Clinical Research, Lilly Research Laboratories, Avenida Industria 30, Alcobendas, Spain.
Curr Med Res Opin. 2009 Nov;25(11):2745-54. doi: 10.1185/03007990903316152.
To test the hypothesis that first-line treatment with atomoxetine provides superior efficacy than placebo for up to 12 weeks in improving the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD).
This double-blind, randomized, placebo-controlled, parallel clinical trial included 151 treatment-naïve children (n = 113) and adolescents (n = 38) with newly diagnosed (< or =3 months) ADHD. Atomoxetine dose was uptitrated from 0.5 to 1.2 mg/kg/day after two weeks. Outcome assessments included the ADHD Rating Scale-IV-Parent-reported Investigator-rated (ADHDRS-IV-Parent:Inv), the Clinical Global Impression of Severity of ADHD (CGI-ADHD-S), and the incidence of adverse events. Mixed-model repeated measures analysis was used to compare scale score changes between groups.
Trial registered at www.clinicaltrials.gov (study internal code: B4Z-XM-LYDM, identifier: NCT00191945).
Most patients were male (79.2%), of caucasian origin (96.0%) and severely ill (72.5%). Their mean age was 10.3 years. Atomoxetine-treated patients showed greater reductions from baseline to week 12 of total ADHDRS-IV-Parent:Inv score than placebo-treated patients (least square mean difference: -7.9 [95% CI: -11.0 to -4.8], corresponding to a large effect size of 0.8). Between-group mean differences increased progressively with treatment exposure from week 6 to 12 (-2.7 [-4.9 to -0.6] for total and -1.6 [-2.9 to -0.3] for inattention scores). At the end of the study, 50% of atomoxetine-treated patients (14% with placebo) showed a reduction > or =40% in total ADHDRS-IV-Parent:Inv score, and only 29% (46% with placebo) were severely ill (by CGI-ADHD-S). Treatment-related adverse events were significantly more frequent with atomoxetine (65.0%) than with placebo (37.3%), the most frequent being decreased appetite and somnolence. Only one case of decreased appetite was rated as severe. No patient discontinued treatment because of adverse events.
A continued improvement of symptoms is expectable until 12 weeks in treatment-naïve ADHD patients treated with atomoxetine as first-line medication. Chief limitations are the small, national sample size and the absence of data beyond the 12-week time-point.
检验如下假设：在长达12周的时间里，使用托莫西汀一线治疗在改善注意缺陷多动障碍（ADHD）症状方面比安慰剂具有更高的疗效。
这项双盲、随机、安慰剂对照、平行临床试验纳入了151例初治的新诊断（≤3个月）ADHD儿童（n = 113）和青少年（n = 38）。两周后托莫西汀剂量从0.5mg/kg/天滴定至1.2mg/kg/天。结果评估包括ADHD评定量表第四版家长报告-研究者评定版（ADHDRS-IV-Parent:Inv）、ADHD严重程度临床总体印象量表（CGI-ADHD-S）以及不良事件发生率。采用混合模型重复测量分析比较组间量表评分变化。
该试验在www.clinicaltrials.gov注册（研究内部代码：B4Z-XM-LYDM，标识符：NCT00191945）。
大多数患者为男性（79.2%），白种人（96.0%），病情严重（72.5%）。他们的平均年龄为10.3岁。与安慰剂治疗组患者相比，托莫西汀治疗组患者从基线至第12周ADHDRS-IV-Parent:Inv总分降低幅度更大（最小二乘均数差值：-7.9 [95%置信区间：-11.0至-4.8]，对应大效应量0.8）。从第6周治疗至第12周，组间平均差值随治疗时间逐渐增加（总分-2.7 [-4.9至-0.6]，注意力不集中评分-1.6 [-2.9至-0.3]）。在研究结束时，50%的托莫西汀治疗患者（安慰剂组为14%）ADHDRS-IV-Parent:Inv总分降低≥40%，且只有29%（安慰剂组为46%）病情严重（根据CGI-ADHD-S评定）。托莫西汀治疗相关不良事件显著多于安慰剂（65.0% 比37.3%），最常见的是食欲减退和嗜睡。只有1例食欲减退被评为严重。没有患者因不良事件停药。
对于以托莫西汀作为一线药物治疗的初治ADHD患者，预计症状持续改善可达12周。主要局限性在于样本量小且来自单一国家，以及缺乏12周时间点之后的数据。
