BACKGROUND The relatively short durations of the initial pivotal randomized placebo-controlled trials involving atomoxetine HCl for the treatment of attention-deficit/hyperactivity disorder (ADHD) provided limited insight into the time courses of ADHD core symptom responses to this nonstimulant, selective norepinephrine reuptake inhibitor. The aim of this analysis was to evaluate time courses of treatment responses or remission, as assessed by attainment of prespecified scores on the ADHD Rating Scale-IV-Parent Version: Investigator Administered and Scored (ADHDRS-IV-PI) and the Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) scales, during up to 1 year of atomoxetine treatment in children with ADHD. METHODS Using pooled data from three Canadian open-label studies involving 338 children ages 6-11 years with ADHD who were treated with atomoxetine for 3, 6 and 12 months, and survival analysis methods for interval-censored data, we estimated the time to: 1) improvement and robust improvement defined by ≥25% and ≥40% reductions from baseline ADHDRS-IV-PI total scores, respectively; and 2) remission using two definitions: a final score of ADHDRS-IV-PI ≤18 or a final score of CGI-ADHD-S ≤2. RESULTS The median time to improvement was 3.7 weeks (~1 month), but remission of symptoms did not occur until a median of 14.3 weeks (~3.5 months) using the most stringent CGI-ADHD-S threshold. Probabilities of robust improvement were 47% at or before 4 weeks of treatment; 76% at 12 weeks; 85% at 26 weeks; and 96% at 52 weeks. Probabilities of remission at these corresponding time points were 30%, 59%, 77%, and 85% (using the ADHDRS-IV scale) and 8%, 47%, 67%, and 75% (using the CGI-ADHD-S scale). The change from atomoxetine treatment month 5 to month 12 of -1.01 (1.03) was not statistically significant (p = .33). CONCLUSIONS Reductions in core ADHD symptoms during atomoxetine treatment are gradual. Although approximately one-half of study participants showed improvement at 1 month of atomoxetine treatment, remission criteria were not met until about 3 months. Understanding the time course of children's responses to atomoxetine treatment may inform clinical decision making and also influence the durations of trials comparing the effects of this medication with other ADHD treatments. TRIAL REGISTRATIONS clinicaltrials.gov: NCT00191633, NCT00216918, NCT00191880.

中文翻译：

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托莫西汀治疗注意力缺陷/多动障碍儿童的改善和症状缓解时间进程：加拿大开放标签研究分析。

背景 涉及盐酸托莫西汀治疗注意力缺陷/多动障碍 (ADHD) 的初始关键性随机安慰剂对照试验的持续时间相对较短，但对这种非刺激性、选择性去甲肾上腺素再摄取抑制剂的 ADHD 核心症状反应的时间过程提供了有限的了解. 该分析的目的是评估治疗反应或缓解的时间过程，通过在 ADHD 评定量表-IV-父母版本：调查员管理和评分 (ADHDRS-IV-PI) 和临床总体印象中达到预先指定的分数来评估-ADHD-严重程度 (CGI-ADHD-S) 量表，在多动症儿童接受托莫西汀治疗长达 1 年期间。方法 使用来自三项加拿大开放标签研究的汇总数据，这些研究涉及 338 名 6-11 岁的 ADHD 儿童，他们接受了托莫西汀治疗 3、6 和 12 个月，并使用间隔删失数据的生存分析方法，我们估计时间： 1) 分别由基线 ADHDRS-IV-PI 总分降低≥25% 和≥40% 定义的改进和稳健改进；2) 缓解使用两种定义：ADHDRS-IV-PI 的最终分数≤18 或 CGI-ADHD-S 的最终分数 ≤2。结果 改善的中位时间为 3.7 周（~1 个月），但直到使用最严格的 CGI-ADHD-S 阈值的中位时间为 14.3 周（~3.5 个月）后症状才出现缓解。在治疗 4 周时或之前，明显改善的概率为 47%；12 周时为 76%；26 周时为 85%；52 周时为 96%。在这些相应时间点的缓解概率分别为 30%、59%、77% 和 85%（使用 ADHDRS-IV 量表）和 8%、47%、67% 和 75%（使用 CGI-ADHD-S规模）。从托莫西汀治疗第 5 个月到第 12 个月的变化为 -1.01 (1.03) 无统计学意义 (p = .33)。结论托莫西汀治疗期间核心 ADHD 症状的减轻是逐渐的。尽管大约一半的研究参与者在托莫西汀治疗 1 个月时表现出改善，但直到大约 3 个月才达到缓解标准。了解儿童对托莫西汀治疗反应的时间过程可能会为临床决策提供信息，也会影响比较这种药物与其他 ADHD 治疗效果的试验持续时间。试验注册clinicaltrials.gov：NCT00191633、NCT00216918、NCT00191880。