Clinical trial NCT03114098: Pharmacogenetics Anomaly Research in Children and Adolescents With Pharmacological Resistance to Psychotropic Drugs
Official title: Personalized Medicine: Pharmacogenetics Anomaly Research in Children and Adolescents With Pharmacological Resistance to Psychotropic Drugs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Drug Resistance
Psychotropic Drugs
Keywords: Drug Resistance
CYP2D6
cytochrom P450
Lead sponsor: Fondation Lenval
Sponsor class: OTHER
First posted: 2017-04-14
Enrollment: 22
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: prevalence of a CYP2D6 duplication or polymorphisms
timeFrame: At baseline
Secondary outcomes:
measure: Psychiatric diagnosis and comorbidities
timeFrame: At baseline
measure: Global Severity of illness
timeFrame: At baseline
measure: Severity of illness for children
timeFrame: At baseline
measure: Current and previous psychotropic treatment
timeFrame: At baseline
measure: Side effects in different psychotropic treatments
timeFrame: At baseline
measure: New anomalies of CYP2D6 gene
timeFrame: At baseline
measure: Description of the clinical phenotype of patients
timeFrame: At baseline
Other outcomes:
Locations:
city: Nice
country: France
facility: Fondation Lenval Hôpitaux Pédiatriques de Nice CHU-LENVAL
Study officials:
affiliation: Fondation Lenval Hôpitaux Pédiatriques de Nice CHU-LENVAL
name: Susanne THÜMMLER, MD
role: PRINCIPAL_INVESTIGATOR
References: