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Completed

NCT Number: NCT03114098

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

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.

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Key information

Age range

Up to 18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Fondation Lenval Hôpitaux Pédiatriques de Nice CHU-LENVAL

Nice, 06200, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

gene abnormalities

Other

A salivary sample (2 ml sample) Blood sampling will be performed to assess treatment tolerance (6 ml)

Primary outcomes

  1. prevalence of a CYP2D6 duplication or polymorphisms

    Time frame: At baseline

    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

Secondary outcomes

  1. Psychiatric diagnosis and comorbidities

    Time frame: At baseline

    Diagnostic and Statistical Manual of Mental Disorders 5 DSM5

  2. Global Severity of illness

    Time frame: At baseline

    Clinical Global Impression scale (échelle CGI-I)

  3. Severity of illness for children

    Time frame: At baseline

    Children's Global Assessment Scale (CGAS)

  4. Current and previous psychotropic treatment

    Time frame: At baseline

    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.

  5. Side effects in different psychotropic treatments

    Time frame: At baseline

    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

  6. New anomalies of CYP2D6 gene

    Time frame: At baseline

    To look for any other abnormality of the CYP2D6 gene not known to be associated with an ultrafast metabolizing phenotype

  7. Description of the clinical phenotype of patients

    Time frame: At baseline

    The characterization of the clinical phenotype will be carried out on the one hand by the standardized diagnostic interview MINI Mini International Neuropsychiatric Interview

Sponsors and collaborators

Lead sponsor

Fondation Lenval

Other

Registry information

Official study title

Personalized Medicine: Pharmacogenetics Anomaly Research in Children and Adolescents With Pharmacological Resistance to Psychotropic Drugs

Acronym: M4P

Important dates

Study start
2016
Primary completion
2018
Study completion
2019
First posted
Apr 14, 2017
Registry last updated
Feb 26, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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