Pédopsychiatrie et pharmacogénétique : pharmacorésistance aux psychotropes et duplication du cytochrome P450 2D6, à propos de trois cas cliniques

Abstract

Severe mental health diseases in children and adolescents–such as schizophrenia, bipolar disorder or depression–are chronic impairing diseases representing a major public health issue. Despite adequate pharmacological treatment, some patients will present pharmacoresistant disease and in consequences psychotropic poly-therapy. Those patients are at more important risk to present adverse advents as well as longer in- our outpatient treatment. Psychotropics are predominantly metabolised at hepatic level, and for a high number of them by cytochrome P450 and its CYP2D6 subunit. A functional abnormality of this subunit induces a dysfunctioning of metabolisation of these treatments (inefficiency or adverse events). Several studies demonstrated a link between pharmacogenetics and treatment efficiency. This clinical presentation describes three pharmacoresistant patients aged between 13 and 16 years. All presented psychiatric disease since several years and requiring one or several full-time hospitalisation in a child and adolescent psychiatry department. Psychotropic treatments with market authorization or frequently used in our speciality had been without clinical efficiency for the symptomatology of these adolescents. As a consequence, clinical management implicated poly-therapy, adverse events and repeated hospitalisation with a high impact on social, family and school functioning. In this context of pharmacoresistance, pharmacogenetic testing has been realised. Two patients presented functional pharmacogenetic anomalies of cytochrome P450 2D6 and were ultrarapid metaboliser for CYP2D6. Accordingly, treatment decisions had been revised using psychotropics not metabolized by CYP2D6 as well as non-pharmacological approaches. This readjustement was followed by clinical improvement and psychosocial rehabilitation. The third patient we describe did not present a pharmacogenetic abnormality of CYP2D6, thus illustrating the complex mechanism of pharmacoresistance, not only explained by CYP2D6 dysfunctioning. This clinical case also allows questioning about our clinical practices.