Pharmacogenetic approach for a better drug treatment in children.
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.


CONCLUSIONS
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, mainly if a priori conceptual hypothesis and rigorous methodological strategies are followed. 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.
Polanczyk
Guilherme
G
Department of Psychiatry, University of São Paulo Medical School, Brazil.
Bigarella
Marcelo P
MP
Hutz
Mara H
MH
Rohde
Luis Augusto
LA
D000293:Adolescent; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics; D002648:Child; D002986:Clinical Trials as Topic; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D006801:Humans; D008774:Methylphenidate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011437:Propylamines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000069445:Atomoxetine Hydrochloride; D050483:Dopamine Plasma Membrane Transport Proteins; D008774:Methylphenidate; D011437:Propylamines; D050638:Receptors, Dopamine D4; D017367:Selective Serotonin Reuptake Inhibitors; C493599:DRD4 protein, human; C493214:SLC6A3 protein, human