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Psychotropic drugs are frequently used in children and adolescents in France with a prescription rate of 2.5%. Antipsychotics (PA) and antidepressants (AD), each concern 0.3% of the pediatric population (Kovess et al., 2015). Despite appropriate pharmacological treatment, some patients are drug-resistant and have persisting symptoms and ineffective psychotropic treatments. These children and adolescents are generally exposed to many psychotropic molecules and often to poly-therapy.
Most psychotropic treatments, especially AP and AD, are metabolised at the hepatic level by cytochrome P450 and in particular by CYP2D6. Duplication / multiplication of the CYP2D6 gene induces too rapid metabolism of drugs.
Demonstration of a CYP2D6 abnormality has a direct impact on the management of the patient and on the clinical decisions of the clinician. Thus, knowledge of individual metabolism will decrease the failure of treatment, improve quality of life and therapeutic compliance.
Psychotropic drugs are frequently used in children and adolescents in France with a prescription rate of 2.5%. Antipsychotics (PA) and antidepressants (AD) each concern 0.3% of the pediatric population (Kovess et al., 2015). Despite appropriate pharmacological treatment, some patients are drug-resistant and have persisting symptoms and ineffective psychotropic treatments. These children and adolescents are generally exposed to many psychotropic molecules and often to poly-therapy. Additionally, hospitalizations for child psychiatry, sometimes of prolonged duration, are frequent for these patients. In France, to date, the psychiatrist practitioner rarely uses pharmacogenetic evaluation as a complementary tool for prescribing psychotropic drugs. Nevertheless, an individualized prescription taking into consideration the patient's individual metabolism could greatly improve the benefit and reduce the risk of psychotropic treatments in the pediatric population.
Most psychotropic treatments, especially AP and AD, are metabolised at the hepatic level by cytochrome P450 and in particular by CYP2D6. Duplication / multiplication of the CYP2D6 gene induces too rapid metabolism of the drugs (ultrafast metabolizer). It is linked to a clinical inefficiency of treatments, and concerns up to 10% of the general population in southern Europe (Scordo et al., 2004).
In a preliminary study in Nice, an abnormality of CYP2D6 was found in 4 of the 7 patients tested with drug-resistant and / or with numerous adverse effects to the AP, of which 3 of the 5 pharmacologically resistant patients shows a duplication of the gene.
Demonstration of a CYP2D6 abnormality has a direct impact on the management of the patient and on the clinical decisions of the clinician. Thus, knowledge of individual metabolism will decrease the failure of treatment, improve quality of life and therapeutic compliance.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CYP2D6 gene abnormalities | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| gene abnormalities | Other | A salivary sample (2 ml sample) Blood sampling will be performed to assess treatment tolerance (6 ml) |
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| Measure | Description | Time Frame |
|---|---|---|
| prevalence of a CYP2D6 duplication or polymorphisms | study the prevalence of a CYP2D6 duplication or polymorphisms associated with an ultrafast metabolizing phenotype in a population of children and adolescents who are drug-resistant to antipsychotic and antidepressant psychotropic drugs. performed by analysis of salivar sample | At baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Psychiatric diagnosis and comorbidities | Diagnostic and Statistical Manual of Mental Disorders 5 DSM5 | At baseline |
| Global Severity of illness | Clinical Global Impression scale (échelle CGI-I) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Susanne THÜMMLER, MD | Fondation Lenval Hôpitaux Pédiatriques de Nice CHU-LENVAL | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fondation Lenval Hôpitaux Pédiatriques de Nice CHU-LENVAL | Nice | 06200 | France |
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| At baseline |
| Severity of illness for children | Children's Global Assessment Scale (CGAS) | At baseline |
| Current and previous psychotropic treatment | Number of different molecules (antipsychotic antidepressant) used during the therapeutic history of the patient, duration of treatment with each molecule, type and maximum dose of current and previous psychotropic treatments. | At baseline |
| Side effects in different psychotropic treatments | Type and severity of the adverse effects identified during the various psychotropic treatments will be collected. This collection will be carried out through the interrogation and study of the medical file | At baseline |
| New anomalies of CYP2D6 gene | To look for any other abnormality of the CYP2D6 gene not known to be associated with an ultrafast metabolizing phenotype | At baseline |
| Description of the clinical phenotype of patients | The characterization of the clinical phenotype will be carried out on the one hand by the standardized diagnostic interview MINI Mini International Neuropsychiatric Interview | At baseline |