Effect of Atomoxetine on Behavioral Difficulties and Growth Development of Primary School Children with Attention-Deficit/Hyperactivity Disorder: A Prospective Study

(1) Objective: Atomoxetine is a selective norepinephrine reuptake inhibitor used to treat attention-deficit/hyperactivity disorder (ADHD) in children over six years old. Although it is common knowledge that primary school children with ADHD often present with difficulties in the morning prior to school and in the evening, these two periods, and the family interactions they involve, are often neglected in studies of ADHD. Questionnaire-Children with Difficulties (QCD) has been widely used in China to evaluate parents' perceptions of ADHD and patients' daily behaviors during different times. In the long term, the efficacy and safety of atomoxetine have been well established in previous studies. Still, the short-term effects of atomoxetine treatment on serum growth parameters, such as IGF-1, IGFBP-3, and thyroid function, are not well documented. Therefore, this study was the first one using the QCD to quantify the efficacy of atomoxetine treatment in the morning prior to school and in the evening, and has investigated the possible influence on the growth parameters of Chinese primary school children with ADHD. (2) Method: This prospective study was conducted at the Department of Pediatrics at the Affiliated Hospital of Jiangnan University from August 2019 to February 2021. Changes in the children's behavior and core ADHD symptoms following treatment were assessed using three parent-reported questionnaires, including Children with Difficulties (QCD), the Swanson, Nolan, and Pelham IV scale (SNAP-IV), and the Conners' parents rating scales (CPRS). The height, weight, and body mass index (BMI) were measured and corrected to reflect the standard deviations (SDS) in Chinese children based on age and gender. Serum growth parameters, such as insulin-like growth factor 1 (IGF-1), insulin-like growth factorbinding protein 3 (IGFBP-3), and thyroid function, were also measured to assess the children's growth development. Any adverse drug reactions were assessed every three weeks. (3) Result: Finally, 149 children were enrolled in this study, and they completed 12 weeks of atomoxetine treatment. The QCD results indicated that the atomoxetine treatment could significantly alleviate behavioral difficulties in primary children with ADHD, especially in the morning prior to school (p < 0.001, r = 0.66) and in the evening (p < 0.001, r = 0.73). A statically significant decrease in weight SDS (p < 0.05) was noted during treatment, but the effect size was slight (r = 0.09). The atomoxetine treatment had no significant impact on height SDS, BMI SDS, and serum growth parameters, such as the levels of IGF-1, IGFBP-3, and thyroid function. The SNAP-IV results showed a significant improvement in the core symptoms of ADHD, while the CPRS results indicated a significant improvement in controlling ADHD symptoms across two different domains, learning problems (r = 0.81) and hyperactivity (r = 0.86). No severe adverse reactions were observed in the course of treatment, and the most common adverse reactions were gastrointestinal symptoms. (4) Conclusions: Atomoxetine is an effective and safe treatment for primary school children with ADHD. In China, it may be an excellent choice to alleviate parenting stress and improve the condition of primary school children with ADHD. Moreover, our study indicated that the serum levels of IGF-1 and IGFBP-3 were within the normal range in newly diagnosed ADHD children, and atomoxetine will not affect the serum concentration of growth parameters, such as IGF-1, IGFBP-3, and thyroid function, in the short term. However, the treatment may reduce appetite, resulting in a reduction in the Children's weight for a short period. Further observational studies to monitor the long-term effects of atomoxetine on primary school children are recommended.