Pharmacogenetic Approach for a Better Drug Treatment in Children

Guilherme      Polanczyk; Marcelo      P. Bigarella; Mara      H. Hutz; Luis      Augusto Rohde

Abstract

Objective: We conducted a systematic review of the literature aiming to identify original studies that have evaluated the effect of genes on the response to medications used to treat psychiatric disorders in children and adolescents. Results: We included 35 original studies on the pharmacogenetics of childhood psychiatric disorders. Thirty-three studies addressed the association between genes, particularly dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4), and response to medication for the treatment of attention-deficit/hyperactivity disorder (ADHD). Only two studies investigated atomoxetine as the pharmacological intervention, and the other 31 studies investigated methylphenidate (MPH). One study assessed children with depression and anxiety disorders and another assessed children with autism; in both of them selective serotonin reuptake inhibitors (SSRIs) were the pharmacological intervention. Conclusion: The existing literature on the pharmacogenetics of ADHD suggests that response to MPH is influenced by several different polymorphisms, each one exerting a small effect. Genome-wide association studies and multi-center collaborative projects are likely to overcome the barriers for the development of the field. Future investigations should evaluate, besides improvement of symptoms, emergence of clinically relevant side effects. The lessons we have learned from the progress of the pharmacogenetics of ADHD can be relevant for developing pharmacogenetic studies in other child and adolescent psychiatric disorders.

Keywords: Atomoxetine, childhood mental disorders, pharmacogenetics, pharmacogenomics, ADHD, depression, autism, methylphenidate, selective serotonin reuptake inhibitor