A French community-based intervention for parents of French-Canadian children with behavior problems: The EQUIPE program.

OBJECTIVES: Behavior problems are one of the most common reasons for seeking mental health services in pediatric populations. The objectives are to evaluate the effects of the EQUIPE program (Étude Québécoise d'Intervention pour les Parents d'Enfants avec des problèmes de comportement) and to analyze the impact of the severity of behavior problems and of parental characteristics. METHODS: This program was translated from the Community Parent Education Program. The effects of EQUIPE, as compared to a control group, were evaluated by using Child Behavior Checklist and Parent Stress Index questionnaires before (T0) and after the intervention program (T1), and at 6 (T2) and 12months (T3) follow-up visits. RESULTS: In total, 533 participants were enrolled in intervention (n=465) (with "severe" or "mild" subgroups according to CBCL-T score) and a control group (n=68). In the two groups, the results showed a statistically significant decrease in Child Behavior Checklist and Parent Stress Index total scores at T1, T2 and T3, with the exception of Child Behavior Checklist total scores in the control group at T2. In the intervention group Child Behavior Checklist total scores were significantly higher in the "severe"; which was not the case for Parent Stress Index total scores at T2 and T3. DISCUSSION: Socioeconomic characteristics, family details, parental medical history and the age of the children appeared to influence changes in Child Behavior Checklist and Parent Stress Index total scores. CONCLUSION: The EQUIPE program is an effective intervention for reducing behavior problems and parents' stress in a French-Canadian population.

[Pharmacoresistance to psychotropic drugs in children and adolescents: Pharmacogenetic anomalies of cytochrome P450 2D6]. / La pharmacorésistance aux psychotropes chez l'enfant et l'adolescent : recherche d'anomalies pharmacogénétiques du cytochrome P450 2D6.

OBJECTIVES: Some patients in child and adolescent psychiatry present resistance to psychotropic drugs, often resulting in polytherapy, an increased risk of adverse events, and more frequent and longer hospitalisation. Psychotropic drugs are mainly metabolised in the liver, in particular by the CYP2D6 subunit of cytochrome P450. Anomalies such as a duplication of the CYP2D6 gene related to an ultra-rapid metaboliser phenotype has been described to be linked to clinical efficacy. However, little research has been done in child and adolescent psychiatry. METHODS: A multi-centric cross-sectional study in the southeast of France explored the relation between pharmaco-resistance to psychotropic drugs and the prevalence of duplications or polymorphisms of CYP2D6 associated with an ultra-rapid phenotype in children and adolescents with severe mental health disease. RESULTS: Twenty-two patients have been included. The presence of an ultra-rapid phenotype concerns one patient in our study. A second patient presents a slow metaboliser phenotype. CONCLUSIONS: This study allows a clinical characterisation of the population of pediatric drug-resistant patients whose severity and the impact of their pathology are major and require long-term care associated with repeated hospitalisations, multiple drug prescriptions and numerous side effects. However, a link between drug resistance to psychotropic drugs and CYP2D6 UFM abnormalities could not be confirmed. An additional pharmacogenetic analysis by a panel of genes applied in the metabolism, transport and action of psychotropic drugs should be considered to answer questions about the resistance and independent effects of CYP2D6.

[Carbamazepine and psychotropic treatment interaction: Two case studies of carbamazepine overdosage]. / Surdosage en carbamazépine par interaction avec les psychotropes : à propos de deux cas.

Drug interaction is a frequent situation in pediatrics and child psychiatry. Carbamazepine (CBZ) is an antiepileptic drug used as a mood stabilizer in child psychiatry. CBZ is known to be a potent inducer of various CYP isoenzymes of cytochrome P450, which might result in a decrease in the plasma concentration of associated treatments. We describe two cases of CBZ overdosage in adolescent inpatients (14 and 16 years). The patients were treated with risperidone associated with fluoxetine in one and with loxapine in the other case, and CBZ was introduced as a mood stabilizer. Patients presented typical clinical symptoms (fatigue, dizziness, gastrointestinal signs, blurred vision). Overdosage was confirmed by an elevated CBZ plasma concentration (17 and 15.5 mg/L, therapeutic range 4-12 mg/L). We recommend introducing CBZ very progressively in patients treated with psychotropics, particularly when it is associated to several treatments. An intensification of clinical and biological follow-up with early plasma concentration testing should allow for better treatment adjustment.

[Improve safety monitoring of antipsychotics in the French pediatric population]. / Améliorer la surveillance de la tolérance pédiatrique des antipsychotiques en France.

In France, as in the rest of the world, the prescription of second generation antipsychotics is on the rise in the pediatric population. At the same time, the use of first generation antipsychotics continues, although it is declining in France as in other countries. In France, we lack data on the pediatric population to ensure a safe prescription, unlike other countries such as Canada and the United States. This is disturbing when many adverse events, potentially serious for young patients' health (neuromuscular complications, risk factors, cardiovascular problems) are beginning to be identified. This article reports the current French and international knowledge on antipsychotics in the pediatric population. It appears that data in the French population are nearly nonexistent and that the methodological tools used are not always relevant (population already exposed to psychotropic drugs, short studies, debatable rating scale and somatic parameters). Within this context, a safety monitoring procedure for the naive pediatric population treated with antipsychotics was developed (ETAPE study) to determine the incidence of adverse events appearing with these drugs. Safety monitoring during the 12-month study period will include clinical assessments and laboratory testing. These assessments will be performed before treatment and at 1, 3, 6, 9, and 12 months after the introduction of the antipsychotic drug. This study received funding from the National Security Agency of Medicines (ANSM 2012 No. 40). The results should contribute to educating all practitioners (general physicians, pediatricians, psychiatrists, child psychiatrists) on adverse events, helping practitioners with prescribing decisions, reinforcing the French system of monitoring adverse events caused by atypical antipsychotic drugs, and developing recommendations to improve the safety of atypical antipsychotic drugs in child psychiatry.

[Follow-up of a 16-year-old adolescent with early-onset schizophrenia and catatonic symptoms]. / Suivi thérapeutique d'un adolescent de 16ans souffrant de schizophrénie précoce avec symptômes catatoniques.

INTRODUCTION: The aim of this paper is to underline the need of a systematic monitoring (1) of atypical antipsychotics and (2) of catatonic symptoms in child psychiatry. We present in this paper the clinical history of a 16-year-old adolescent inpatient needing a prescription of atypical antipsychotic drug. We present the most relevant results of our clinical monitoring over 7 months. CASE REPORT: A 16-year-old Caucasian male adolescent, by the name of Paul, was admitted in August 2009 to an Adolescent University Psychiatry Unit for an acute psychotic disorder. On admission, he presented paranoid delusion, auditory hallucinations and impulsive movements. The score on the Bush-Francis Catatonia Rating Scale (BFCRS) was 17 (the threshold score for the diagnosis of catatonic symptoms is 2). Laboratory tests showed the lack of blood toxic levels, creatine phosphokinase (CPK) level was 684 IU/L. Paul was treated with clonazepam (0.05 mg/kg/d). This particular day was considered to be day #1 of the clinical drug monitoring. Immediately after, regular follow-up of catatonic symptoms was performed. On day #15, the CPK level returned to normal with improvement of clinical catatonia but with still a score of 4 on the BFCRS scale. Auditory hallucinations and delusion persisted. Risperidone treatment was begun (1mg/d and 1.5mg/d after 24 hours), associated with oral clonazepam (0.05 mg/kg/d). On day #17, after 48 hours of improvement of delusion, the catatonic symptoms rapidly worsened. Risperidone was stopped; Paul was transferred to intensive care where he was treated with clonazepam IV (0.1mg/kg/d). The score on BFCRS scale was 20, Paul presented no fever and the CPK level was below 170 IU/L. The diagnosis was a relapse of the catatonic episode, which was caused by the administration of risperidone. On day #24, no improvement in the state of catatonia was obtained. The treatment was changed with the following combination of medicine: clonazepam (0.1mg/kg/d)-lorazepam (5mg/d)-carbamazepine (10mg/kg/d). With this combination, the state of catatonia improved quickly and on day #31, he was transferred to the adolescent psychiatry unit. However, delusion and hallucinations persisted; a treatment with olanzapine was started at 5mg/d and then progressively increased to 20mg/d for 10 days. On day #115, after 3 months with olanzapine, no improvement of the hallucinatory and delusional symptoms was observed; the diagnosis of early-onset refractory schizophrenia was established. The Therapeutic Drug Monitoring (TDM) confirmed the good compliance; clozapine was introduced and progressively increased up to 250 mg/d. On day #199, after 3 months under clozapine (250 mg/d), the speech was coherent and delusion was rare. During this period, no relapse of the catatonic state was observed. DISCUSSION: In this case, the BFCRS scale was sensitive to catatonic symptom diagnosis. CPK levels vary differently for each atypical antipsychotic and are not a specific complication indicator. In complex cases, the TDM seems useful when choosing atypical antipsychotics. CONCLUSION: The association of two benzodiazepines (clonazepam-lorazepam) with carbamazepin allowed the improvement of catatonic symptoms. Plasma levels of atypical antipsychotics helped the practitioner in deciding the type of care required: plasma levels confirmed the patient's treatment adherence and thus reinforced the choice of clozapine.