Prescrire Int. 2010 Feb;19(105):5-8.
When attention deficit-hyperactivity disorder in children is truly problematic, methylphenidate, an amphetamine, can be tried as a last resort. Methylphenidate has short-term symptomatic efficacy but also many adverse effects, including a risk of sudden death. After having been evaluated, unsuccessfully, in depression, atomoxetine, a noradrenaline reuptake inhibitor, was authorised in some EU member states for use in attention-deficit/hyperactivity disorder. In France it has only received temporary authorisation for prescription on a named-patient basis. Two double-blind trials comparing atomoxetine versus methylphenidate provided somewhat different results, based on a symptom rating scale completed by the investigator after an interview with the parents. In a trial in 516 children treated for 6 weeks, the "response" rate was statistically higher than with methylphenidate (56% versus 45%). In the other trial in 330 children treated for 8 weeks, the response rate was about 80% in both groups. A meta-analysis of 9 placebo-controlled trials in a total of 1828 children showed that atomoxetine was more effective than placebo in the short term. The main adverse effects identified in clinical trials and pharmacovigilance studies conducted in the United Kingdom and the United States were gastrointestinal disorders (abdominal pain, reduced appetite, vomiting, and weight loss) and neuropsychological disorders (drowsiness, irritability, mood swings, aggressive behaviour). A meta-analysis of 12 trials and pharmacovigilance studies showed an increased risk of suicide. Atomoxetine also provokes seizures, arterial hypotension, tachycardia, and hepatic disorders. Little is known about the risk of abuse or dependence, or the long-term efficacy of treatment. Atomoxetine carries a risk of multiple drug interactions due to its metabolism by the cytochrome P450 isoenzyme 2D6 and its inhibitory effect on noradrenaline reuptake. In practice, atomoxetine has a similar safety profile to methylphenidate and is probably less effective. When drug therapy is warranted, it is better to continue to use methylphenidate, despite its adverse effects.
当儿童注意力缺陷多动障碍问题严重时，可尝试将苯丙胺类药物哌甲酯作为最后手段。哌甲酯有短期的症状缓解疗效，但也有许多不良反应，包括猝死风险。去甲肾上腺素再摄取抑制剂托莫西汀在用于抑郁症评估未成功后，在一些欧盟成员国被批准用于注意力缺陷/多动障碍。在法国，它仅获得了基于特定患者的临时处方授权。两项比较托莫西汀与哌甲酯的双盲试验得出了有些不同的结果，这些结果基于研究者在与家长面谈后完成的症状评分量表。在一项对516名儿童进行6周治疗的试验中，“有效”率在统计学上高于哌甲酯治疗组（56%对45%）。在另一项对330名儿童进行8周治疗的试验中，两组的有效率均约为80%。一项对总共1828名儿童进行的9项安慰剂对照试验的荟萃分析表明，托莫西汀在短期内比安慰剂更有效。在英国和美国进行的临床试验和药物警戒研究中确定的主要不良反应是胃肠道疾病（腹痛、食欲减退、呕吐和体重减轻）和神经心理障碍（嗜睡、易怒、情绪波动、攻击行为）。一项对12项试验和药物警戒研究的荟萃分析显示自杀风险增加。托莫西汀还会引发癫痫、动脉低血压、心动过速和肝脏疾病。关于滥用或依赖风险以及治疗的长期疗效知之甚少。由于托莫西汀通过细胞色素P450同工酶2D6代谢并对去甲肾上腺素再摄取有抑制作用，所以存在多种药物相互作用的风险。实际上，托莫西汀的安全性与哌甲酯相似，且可能效果较差。当有必要进行药物治疗时，尽管哌甲酯有不良反应，最好还是继续使用它。
