[Pharmacoresistance to psychotropic drugs in children and adolescents: Pharmacogenetic anomalies of cytochrome P450 2D6]. / La pharmacorésistance aux psychotropes chez l'enfant et l'adolescent : recherche d'anomalies pharmacogénétiques du cytochrome P450 2D6.

ABSTRACT

OBJECTIVES: Some patients in child and adolescent psychiatry present resistance to psychotropic drugs, often resulting in polytherapy, an increased risk of adverse events, and more frequent and longer hospitalisation. Psychotropic drugs are mainly metabolised in the liver, in particular by the CYP2D6 subunit of cytochrome P450. Anomalies such as a duplication of the CYP2D6 gene related to an ultra-rapid metaboliser phenotype has been described to be linked to clinical efficacy. However, little research has been done in child and adolescent psychiatry. METHODS: A multi-centric cross-sectional study in the southeast of France explored the relation between pharmaco-resistance to psychotropic drugs and the prevalence of duplications or polymorphisms of CYP2D6 associated with an ultra-rapid phenotype in children and adolescents with severe mental health disease. RESULTS: Twenty-two patients have been included. The presence of an ultra-rapid phenotype concerns one patient in our study. A second patient presents a slow metaboliser phenotype. CONCLUSIONS: This study allows a clinical characterisation of the population of pediatric drug-resistant patients whose severity and the impact of their pathology are major and require long-term care associated with repeated hospitalisations, multiple drug prescriptions and numerous side effects. However, a link between drug resistance to psychotropic drugs and CYP2D6 UFM abnormalities could not be confirmed. An additional pharmacogenetic analysis by a panel of genes applied in the metabolism, transport and action of psychotropic drugs should be considered to answer questions about the resistance and independent effects of CYP2D6.