Objectives

The acute tolerability of methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD) has been studied mainly in research samples. Taking advantage of the mandatory test-dose procedure required for starting MPH in Italy, this study aimed to assess the incidence of intolerable adverse events after initial exposure to MPH in routine clinical practice.

Methods

The medical records of 480 consecutively treated, previously drug-naïve children and adolescents with ADHD (90% male, mean age 10.6 ± 3.0 years) were retrospectively analyzed. All children received an initial single dose of MPH immediate release (5 or 10 mg) followed by a 4-hour direct medical observation. Heart rate and blood pressure were measured at dosing and 1, 2, and 3 hours afterwards. If the first dose was well tolerated, the child continued treatment with MPH 5–20 mg daily, and was reassessed a week later.

Results

Eleven patients (2.3%, 95% CI 1.1–4.1) interrupted treatment within a week of initiation because of the following adverse events: irritability (n = 3), tics worsening (n = 3), reduced appetite (n = 1), enuresis (n = 1), hallucinations (n = 1), hyperfocus (n = 1), and ‘rebound’ behavioral worsening (n = 1). The most common adverse events were reduced appetite (20%), irritability (14.2%), headache (10.6%), sleep problems (9.4%), stomachache (9.4%), and tics (5%). Intellectual disability increased the risk of any adverse event in general and of irritability in particular. No cardiovascular symptom was clinically reported. However, routine assessments of vital signs during the first 3 hours after the first dose of MPH showed that 9% of the children had a 20% increase in heart rate, 8.8% had a 20% increase in diastolic blood pressure and 4.5% had a 20% increase in systolic blood pressure. Of these, 25.2% still had an elevated heart rate 1 week later.

Conclusions

Among stimulant-naïve children in clinical practice, the incidence of acute MPH intolerance can be estimated to be between 1.2 and 4.1%. An asymptomatic elevation in cardiovascular parameters can be observed in about 1 out of 10 children and warrants monitoring during ongoing treatment.

中文翻译：

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哌醋甲酯在初治多动症儿童中的急性耐受性：对临床实践中自然收集的数据的分析

目标

主要在研究样本中研究了注意缺陷/多动障碍 (ADHD) 儿童对哌醋甲酯 (MPH) 的急性耐受性。利用在意大利开始 MPH 所需的强制性测试剂量程序，本研究旨在评估常规临床实践中初次接触 MPH 后无法耐受的不良事件的发生率。

方法

回顾性分析了 480 名接受过治疗、既往未接受过药物治疗的 ADHD 儿童和青少年（90% 为男性，平均年龄 10.6 ± 3.0 岁）的医疗记录。所有儿童均接受初始单剂 MPH 速释剂（5 或 10 mg），然后进行 4 小时的直接医学观察。在给药时以及给药后 1、2 和 3 小时测量心率和血压。如果第一剂耐受性良好，则该儿童每天继续使用 MPH 5-20 mg 治疗，并在一周后重新评估。

结果

11 名患者 (2.3%, 95% CI 1.1–4.1) 在开始治疗后一周内因以下不良事件中断治疗：易怒 ( n  = 3)、抽搐恶化 ( n  = 3)、食欲下降 ( n  = 1)、遗尿 ( n  = 1)、幻觉 ( n  = 1)、过度专注 ( n  = 1) 和“反弹”行为恶化 ( n = 1)。最常见的不良事件是食欲下降（20%）、易怒（14.2%）、头痛（10.6%）、睡眠问题（9.4%）、胃痛（9.4%）和抽搐（5%）。智力残疾总体上增加了任何不良事件的风险，特别是易激惹的风险。临床上未报告心血管症状。然而，在第一剂 MPH 后的前 3 小时内对生命体征的常规评估显示，9% 的儿童心率增加 20%，8.8% 的儿童舒张压增加 20%，4.5% 的儿童心率增加。收缩压增加 20%。其中，25.2% 的人在 1 周后心率仍然升高。

结论

在临床实践中未使用过兴奋剂的儿童中，急性 MPH 不耐受的发生率估计在 1.2% 至 4.1% 之间。在大约十分之一的儿童中可以观察到心血管参数的无症状升高，并且需要在持续治疗期间进行监测。