Gaillez C, Sorbara F, Perrin E
Département Médical, Unité thérapeutique Système Nerveux Central, Laboratoires Lilly France, 13, rue Pagès, 92158 Suresnes cedex.
Encephale. 2007 Sep;33(4 Pt 1):621-8. doi: 10.1016/s0013-7006(07)92063-1.
Atomoxetine (Strattera) is the first non-stimulant drug to be approved for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children 6 years of age and adolescents. Atomoxetine is a highly specific inhibitor of the presynaptic norepinephrine transporter, with minimal affinity for other transporters or other neurotransmitter receptors. The target dose is 1.2 mg/kg, in a once- or twice-daily oral administration.
Six randomized, double blind, placebo-controlled clinical trials have demonstrated that atomoxetine was more effective than placebo for the treatment of children and adolescents with ADHD. All these trials have shown a consistent improvement in the ADHD rating scale (ADHD-RS) from baseline in the patients treated with atomoxetine, compared with that of the placebo group. The improvement of ADHD symptoms was confirmed by the other secondary efficacy measures (the Clinical Global Impression, CGI, the Conners ADHD rating scale/parent, teacher). The duration of action of atomoxetine on ADHD symptoms extended throughout the waking hours, and the drug effects persisted up to the next morning with a single morning dose. Significant improvements were also observed with atomoxetine compared to placebo, in several aspects of the quality of life measurement (social and family functioning), and the child's self-esteem. In addition, in patients who responded favourably to initial treatment, atomoxetine was shown to be superior to placebo in maintaining a long term-response, up to 18 months. Atomoxetine was effective and safe, both in young children and adolescents with ADHD. Preliminary data also support the potential efficacy of atomoxetine in managing patients with ADHD and comorbid conditions, such as tic disorders, oppositional-defiant and conduct disorders.
As of June 2004, over 3,000 children and adolescents have been enrolled in clinical trials of atomoxetine, with about 1,200 of them treated for more than 1 year and about 400 of them treated for more than 2 years. Atomoxetine was well tolerated in most individuals, the two more common adverse events reported were gastro-intestinal disorders and decreased appetite. These side effects were generally noted to be transient. No significant changes in weight and height gain was reported over the long-term follow-up. There was no evidence of symptoms rebound and no evidence of an acute discontinuation syndrome when discontinuing treatment. In addition, given the mechanism of action of atomoxetine in the central nervous system, and lack of subjective, physiological and psychomotor effects reported in experimental conditions, it is unlikely that atomoxetine would have abuse potential.
Results from clinical trials demonstrated that atomoxetine is effective and well tolerated for the acute and long-term treatment of children and adolescents suffering from ADHD. Atomoxetine should be considered as a new interesting pharmacological option in the treatment of ADHD in association with non pharmacological therapeutic interventions.
托莫西汀（择思达）是首个被批准用于治疗6岁儿童及青少年注意力缺陷多动障碍（ADHD）的非兴奋剂药物。托莫西汀是一种高选择性的突触前去甲肾上腺素转运体抑制剂，对其他转运体或其他神经递质受体的亲和力极低。目标剂量为1.2毫克/千克，每日口服一次或两次。
六项随机、双盲、安慰剂对照临床试验表明，托莫西汀治疗患有ADHD的儿童和青少年比安慰剂更有效。与安慰剂组相比，所有这些试验均显示，接受托莫西汀治疗的患者的ADHD评定量表（ADHD-RS）较基线有持续改善。其他次要疗效指标（临床总体印象量表，CGI；康纳斯ADHD评定量表/家长版、教师版）也证实了ADHD症状的改善。托莫西汀对ADHD症状的作用持续整个清醒时间，单次晨起服药后药物效果可持续至次日早晨。与安慰剂相比，托莫西汀在生活质量测量的几个方面（社会和家庭功能）以及儿童自尊方面也有显著改善。此外，在对初始治疗反应良好的患者中，托莫西汀在维持长达18个月的长期反应方面优于安慰剂。托莫西汀对患有ADHD的幼儿和青少年均有效且安全。初步数据也支持托莫西汀在治疗患有ADHD合并疾病（如抽动障碍、对立违抗和品行障碍）患者中的潜在疗效。
截至2004年6月，超过3000名儿童和青少年参加了托莫西汀的临床试验，其中约1200人接受治疗超过1年，约400人接受治疗超过2年。大多数个体对托莫西汀耐受性良好，报告的两种较常见不良事件为胃肠道疾病和食欲下降。这些副作用通常被认为是短暂的。长期随访未报告体重和身高增长有显著变化。停药时没有症状反弹的证据，也没有急性停药综合征的证据。此外，鉴于托莫西汀在中枢神经系统中的作用机制，以及在实验条件下未报告主观、生理和精神运动效应，托莫西汀不太可能有滥用潜力。
临床试验结果表明，托莫西汀对患有ADHD的儿童和青少年的急性和长期治疗有效且耐受性良好。在与非药物治疗干预联合治疗ADHD时，托莫西汀应被视为一种新的、有吸引力的药理学选择。
