A precision medication study of atomoxetine in children with attention deficit hyperactivity disorder: CYP2D6 genetic testing and therapeutic drug monitoring / 中国当代儿科杂志

Atomoxetine is the first non-stimulant drug for the treatment of children and adults with attention deficit hyperactivity disorder (ADHD), and its safety and efficacy show significant differences in the pediatric population. This article reviews the genetic factors influencing the pharmacokinetic differences of atomoxetine from the aspect of the gene polymorphisms of the major metabolizing enzyme CYP2D6 of atomoxetine, and then from the perspective of therapeutic drug monitoring, this article summarizes the reference ranges of the effective concentration of atomoxetine in children with ADHD proposed by several studies. In general, there is an association between the peak plasma concentration of atomoxetine and clinical efficacy, but with a lack of data from the Chinese pediatric population. Therefore, it is necessary to establish related clinical indicators for atomoxetine exposure, define the therapeutic exposure range of children with ADHD in China, and combine CYP2D6 genotyping to provide support for the precision medication of atomoxetine.

Evaluación de la efectividad y seguridad de la atomoxetina para déficit atencional en población entre 6 y 19 años: revisión sistemática / Effectiveness and safety of atomoxetine for ADHD in population between 6 and 19 years: a systematic review

Introducción: el Trastorno por déficit de atención e hiperactividad (TDAH) dispone de intervenciones farmacológicas como los psicoestimulantes. El más usado es el metilfenidato y posteriormente se ha incluido la atomoxetina. Objetivo: identificar, sintetizar y evaluar la mejor evidencia disponible sobre la efectividad y seguridad de la atomoxetina en el tratamiento en déficit atencional en la población de 6 a 19 años. Métodos: se realizó una revisión sistemática de estudios de intervenciones, que evaluaron efectividad comparada de atomoxetina con placebo y metilfenidato. Las medidas fueron funcionamiento educacional, funcionamiento psicosocial, calidad de vida y efectos adversos. Se consultó en bases de datos hasta febrero de 2012 en inglés y castellano: PubMed, LILACS, Cochrane, DARE y National Guideline Clearinghouse. Los artículos incluidos fueron evaluados por dos investigadores en forma independiente. Resultados: de los 108 estudios encontrados inicialmente, se incluyeron 11, entre ellos 5 revisiones sistemáticas, un artículo primario y 5 guías clínicas. Conclusiones: la atomoxetina se recomienda como segunda opción en el TDAH por ser superior al placebo, cuando falla el metilfenidato o hay presencia de comorbilidades.

Introduction: Attention deficit hyperactivity disorder (ADHD) is generally treated with pharmacological interventions such as psychostimulants. The most used widely used one is methylphenidate followed by atomoxetine. Purpose: To identify, synthesize and evaluate the best available evidence on the effectiveness and safety of atomoxetine in ADHD treatment in the 6-19 year-old population. Methods: A systematic review of intervention studies that evaluated effectiveness of atomoxetine compared with placebo and methylphenidate was conducted. Outcomes assessed were educational functioning, psychosocial functioning, quality of life and adverse effects. The search was done up to February 2012 in English and Spanish in the following databases: PubMed/MEDLINE, LILACS, Cochrane, DARE and National Guideline Clearinghouse. The articles were independently evaluated by two investigators. Results: Of the 108 studies found initially, 11 were included, among which five systematic reviews, one primary article and 5 clinical guidelines. Conclusions: Atomoxetine is recommended as a second option in ADHD and was found to be superior to placebo. Its use is recommended when methylphenidate fails or comorbidities are present.

Attention deficit hyperactivity disorder--a review for family physicians.

Attention deficit hyperactivity disorder (ADHD) is a chronic behavioral disorder characterized by persistent hyperactivity, impulsivity, and inattention that impairs educational achievement and/or social functioning. Its diagnosis is made by ascertaining whether the child's specific behaviors meet the diagnostic and statistical manual of mental disorders-IV-revised criteria. Its etiology is still unclear but recent studies suggest that genetics plays a major role in conferring susceptibility. Comorbidity with psychiatric disorders such as anxiety disorder, depression, oppositional defiant disorder and conduct disorder; and with specific learning disability is not uncommon. Although medication works well in most cases of ADHD, optimal treatment requires integrated medical and behavioral treatment. Methylphenidate (MPH) and atomoxetine are the two drugs being currently prescribed and their efficacy in decreasing the symptoms of ADHD is well documented. Pyschoeducational interventions in school can help increase the successful functioning of affected children and improve their academic performance. Almost half of affected children continue to show significant symptoms of the disorder into adolescence and young adulthood. The family physician can play an important role in detecting this condition early, coordinating its assessment and treatment, counseling the parents and classroom teacher, and monitoring the child's academic and psychosocial progress on a long-term basis.