Pharmacogenetics Anomaly Research in Children and Adolescents With Pharmacological Resistance to Psychotropic Drugs (M4P)

Fondation Lenval

Status: Completed

Conditions: Psychotropic Drugs; Drug Resistance

Treatments: Other: gene abnormalities

Study type: Interventional

Funder types: Other

Identifiers

NCT03114098

16-HPNCL-02

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 22 patients

Sex: All

Ages: Under 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Pharmaco resistance to psychotropic drugs
• Obtaining the informed consent of the patient and his / her parents or legal guardian
• Affiliation to a social security system

Exclusion criteria

• Patient deprived of liberty

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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22 participants in 1 patient group

CYP2D6 gene abnormalities

Experimental group

Description:

* A salivary sample (2 ml sample) which will allow the investigation of an anomaly of the metabolism of psychotropic drug. * Blood sampling will be performed to assess treatment tolerance (6 ml). A sample (4 ml) will be kept for possible future analyzes in relation to the objectives of this study for the recruiting center of Nice. * Electrocardiogram * Clinical exam * Clinical Global Impression Scale (CGI-S) * Children's Global Assessment Scale (CGAS) * Sheehan Disability Scale (SDS) * Wechsler Preschool and Primary Scale of Intelligence III (WPPSI-III ) * Wechsler Intelligence Scale for Children - 4 (WISC-4) * Wechsler Adult Intelligence Scale 4 (WAIS 4) * Diagnostic and Statistical Manual of Mental Disorders (DSM) * Autism Diagnostic Interview (ADI)

Treatment:

Other: gene abnormalities