Background

When children with attention-deficit/hyperactivity disorder (ADHD) are treated with stimulant medication, the dose is established clinically by dose adjustment over time. Little is known about children who are not adequately treated when they reach a designated maximum dose, or the consequences of exceeding this dose.

Objective

The aim of this study was to determine the characteristics of and side effects observed in children optimised to high dose (HD) versus regular dose (RD) stimulants.

Method

Children treated by one paediatrician (AP) in Western Sydney, Australia with HD stimulants (n = 52) were identified using an electronic database; controls on RD stimulant (n = 118) were matched by prescription date with the cases’ first HD prescription. HD was defined as methylphenidate > 2 mg/kg/day or > 108 mg/day; dexamphetamine > 1 mg/kg/day or > 50 mg/day; lisdexamfetamine > 70 mg/day. In all children, the dose was adjusted over time to optimise the clinical response. Clinical characteristics, anthropometric measures, reported side effects and reasons for dose changes were extracted from the clinical charts by LR, VS and CS. The HD and RD cohorts were compared using chi-square for categorical data and t tests for continuous data.

Results

The HD cohort included more boys (88% vs 75%, p = 0.041) and more oppositional defiant disorder (83% vs 55%, p = 0.001). They started stimulants younger (6.40 ± 1.67 vs 8.28 ± 2.77 years, p < 0.001) and had more growth attenuation (Δ height z-score − 0.41 ± 0.55 vs − 0.09 ± 0.58, p = 0.001; Δ weight z-score − 0.56 ± 0.82 vs − 0.18 ± 0.66, p = 0.002). The growth attenuation mainly occurred before the dose reached the HD range. Diminishing stimulant effectiveness was the commonest reason for a dose increase in either cohort, the most prominent recurring symptoms being persistent anger/aggression in the HD and poor concentration in the RD cohort. The commonest reason for dose reduction in the HD cohort was that a dose increase gave no added benefit; dose reduction or change of drug due to subdued/depressed behaviour was more frequent in RD children. Apart from growth attenuation, no serious complications were reported in the HD group.

Conclusions

In this preliminary study, dose adjustment over time in some patients meant using higher doses than those generally recommended. These children experienced more growth attenuation but recorded no other significant treatment complications. Determining the dose purely on clinical grounds by careful dose adjustment over time appears reasonable, but more data on this issue is required to clarify the efficacy and tolerability of exceeding the recommended doses of stimulants when treating ADHD.

中文翻译：

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注意力缺陷/多动障碍儿童兴奋剂的剂量调整：超过推荐剂量影响的回顾性图表审查。

背景

当患有注意力缺陷/多动障碍 (ADHD) 的儿童接受兴奋剂药物治疗时，临床上通过随时间调整剂量来确定剂量。对达到指定最大剂量时未得到充分治疗的儿童，或超过此剂量的后果知之甚少。

客观的

本研究的目的是确定在优化高剂量 (HD) 与常规剂量 (RD) 兴奋剂的儿童中观察到的特征和副作用。

方法

 使用电子数据库识别由澳大利亚西悉尼的一名儿科医生 (AP) 使用 HD 兴奋剂 ( n = 52)治疗的儿童；RD 兴奋剂的对照（n  = 118）按处方日期与病例的第一个 HD 处方匹配。HD 定义为哌甲酯 > 2 mg/kg/天或 > 108 mg/天；右苯丙胺 > 1 mg/kg/天或 > 50 mg/天；lisdexamfetamine > 70 毫克/天。在所有儿童中，随着时间的推移调整剂量以优化临床反应。通过 LR、VS 和 CS 从临床图表中提取临床特征、人体测量学测量、报告的副作用和剂量变化的原因。HD 和 RD 队列的比较使用分类数据的卡方和连续数据的t检验。

结果

HD 队列包括更多男孩（88% 对 75%，p  = 0.041）和更多对立违抗性障碍（83% 对 55%，p  = 0.001）。他们开始使用更年轻的兴奋剂（6.40 ± 1.67 vs 8.28 ± 2.77 岁，p  < 0.001）并且生长衰减更大（Δ height z -score - 0.41 ± 0.55 vs - 0.09 ± 0.58, p  = 0.001; Δ weight z -score - ± 0.82 与 − 0.18 ± 0.66，p = 0.002）。生长衰减主要发生在剂量达到 HD 范围之前。兴奋剂有效性降低是任一组中剂量增加的最常见原因，最突出的复发症状是 HD 中持续的愤怒/攻击性和 RD 组中的注意力不集中。在 HD 队列中减少剂量的最常见原因是剂量增加没有带来额外的好处；在 RD 儿童中，由于行为抑制/抑郁而减少剂量或改变药物的情况更为常见。除了生长减慢外，HD组没有报告严重的并发症。

结论

在这项初步研究中，随着时间的推移，一些患者的剂量调整意味着使用比通常推荐的更高的剂量。这些儿童经历了更多的生长衰减，但没有记录到其他显着的治疗并发症。通过随时间仔细调整剂量来完全根据临床确定剂量似乎是合理的，但需要更多关于这个问题的数据来阐明治疗 ADHD 时超过推荐剂量的兴奋剂的疗效和耐受性。