Preliminary and ongoing French multicenter prospective naturalistic study of adverse events of antipsychotic treatment in naive children and adolescents

Chinese Medicine

Florence Askenazy²  Philippe Auby¹  Susanne Thümmler²  Marie-Line Menard² 

[1]Paediatrics and CDC, Lundbeck SAS, 92445 Issy-les-Moulineaux, France

[2]University Department of Child and Adolescent Psychiatry, Nice Children's Hospitals CHU-Lenval, 57 avenue de la Californie, 06200 Nice, France

关键词: Pediatrics;    Child psychiatry;    Drug-naïve population;    Therapeutic drug monitoring;    Antipsychotics;    Adverse drug events;   

Others  :  790403
DOI  :  10.1186/1753-2000-8-18

 received in 2014-02-22, accepted in 2014-06-02,  发布年份 2014

【 摘 要 】

Background

The prescription of antipsychotics (AP), and especially second generation AP, is increasing worldwide in the pediatric population. Most prescriptions are off-label and despite the identification of frequent and potentially severe adverse events (AE), there are only a few guidelines for the safety management. France is one of the countries with no official safety guidelines.

Methods

Psychotropic drug-naive adolescents (13–18 years), hospitalized for an acute psychotic episode and treated with a second-generation antipsychotic were consecutively included in a prospective cohort study. Patients were assessed for their AE at baseline, 2, 6 and 12 weeks after the introduction of drug.

Results

The majority of patients was treated with risperidone (n = 13), 2 with aripiprazole. The principal findings are: (1) A high incidence of neuromuscular AE: 8/15 muscle weakness, 8/15 extrapyramidal syndrome, 6/15 akathisia, 3/15 oro-facial acute dystonia; (2) Severe catatonia symptoms in 2 patients despite a low to moderate treatment dose, requiring transfer in intensive care unit for one; (3) Weight gain and significant increase of the BMI for all 13 patients who had a 12 weeks follow-up.

Conclusion

All adolescents experienced AE, with significant weight gain being observed in all patients who completed the 12-week follow-up. The fact that our patient population was first episode drug naïve may partially explain this observation. Despite the limitation due to the small sample size of this prospective short-term study, such findings are important to report and warrant further research.

Clinical and research implication

Because of the lack of naturalistic follow up studies of antipsychotic treatments in AP-naive children and adolescents and the absence of safety guidelines for the pediatric population in France, we decided to continue our research at a national level. We therefore started a prospective, naturalistic and multicenter study funded by the French National Agency for Medicines and Health Products Safety (ANSM). Study purpose is to evaluate the incidence of adverse events related to antipsychotic drugs in AP-naive children and adolescents. In addition, we aim to provide further evidence for the necessity of national safety guidelines for AP prescription in the pediatric population.

【 授权许可】

   
2014 Menard et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Wong IC, Murray ML, Camilleri-Novak D, Stephens P: Increased prescribing trends of paediatric psychotropic medications. Arch Dis Child 2004, 89:1131-1132.
• [2]Acquaviva E, Peyre H, Falissard B: Panorama de la prescription et de la consommation des psychotropes chez l’enfant et l’adolescent en France. Neuropsychiatr Enf Adolesc 2012, 60:77-85.
• [3]Patel NC, Crismon ML, Hoagwood K, Johnsrud MT, Rascati KL, Wilson JP, Jensen PS: Trends in the use of typical and atypical antipsychotics in children and adolescents. J Am Acad Child Adolesc Psychiatry 2005, 44:548-556.
• [4]Kumra S, Oberstar JV, Sikich L, Findling RL, McClellan JM, Vinogradov S, Schulz SC: Efficacy and tolerability of second-generation antipsychotics in children and adolescents with schizophrenia. Schizophr Bull 2008, 34:60-71.
• [5]Harrison JN, Cluxton-Keller F, Gross D: Antipsychotic medication prescribing trends in children and adolescents. J Pediatr Health Care 2012, 2:139-145.
• [6]Vitiello B, Correll C, van Zwieten-Boot B, Zuddas A, Parellada M, Arango C: Antipsychotics in children and adolescents: Increasing use, evidence for efficacy and safety concerns. Eur Neuropsychopharmocol 2009, 19:629-635.
• [7]Matone M, Localio R, Huang YS, dosReis S, Feudtner C, Rubin D: The relationship between mental health diagnosis and treatment with second-generation antipsychotics over time: a national study of U.S. Medicaid-enrolled children. Health Serv Res 2012, 47:1836-1860.
• [8]Fraguas D, Correll CU, Merchan-Naranjo J, Rapado-Castro M, Parellada M, Moreno C, Arango C: Efficacy and safety of second-generation antipsychotics in children and adolescents with psychotic and bipolar spectrum disorders: comprehensive review of prospective head-to-head and placebo-controlled comparisons. Eur Neuropsychopharmacol 2011, 21:621-645.
• [9]Zuddas A, Zanni R, Usala T: Second generation antipsychotics (SGAs) for non-psychotic disorders in children and adolescents: a review of the randomized controlled studies. Eur Neuropsychopharmacol 2011, 21:600-620.
• [10]Bonnot O, Holzer L: Utilisation des antipsychotiques chez l’enfant et l’adolescent. Neuropsychiatr Enf Adolesc 2012, 60:12-19.
• [11]Cohen D, Bonnot O, Bodeau N, Consoli A, Laurent C: Adverse effects of second-generation antipsychotics in children and adolescents: A Bayesian meta-analysis. J Clin Psychopharmacol 2012, 32:309-316.
• [12]Bonnot O, Inaoui R, Raffin-Viard M, Bodeau N, Coussieu C, Cohen D: Children and adolescents with severe mental illness need Vitamin D supplementation regardless of disease or treatment. J Child Adolesc Psychopharmacol 2011, 21:157-161.
• [13]Correll CU, Kane JM, Manu P: Obesity and coronary risk in patients treated with second-generation antipsychotics. Eur Arch Psychiatry Clin Neurosci 2011, 261:417-423.
• [14]Goeb JL, Duhamel A, Kechida G, Bordetd R, Thomase P, Deliona P, Jardria R: Effets secondaires métaboliques de la risperidone dans les schizophrénies à début précoce. Encéphale 2010, 36:242-252.
• [15]Woods SW, Martin A, Spector SG, McGlashan TH: Effects of development on olanzapine associated adverse events. J Am Acad Child Adolesc Psychiatry 2002, 41:1439-1446.
• [16]Merchán-Naranjo J, Tapia C, Bailón C, Moreno C, Baeza I, Calvo-Escalona R, Morer A, Martínez-Cantarero C, Nestares PA, Alda JÁ, Muñoz D, Arango C: Secondary effects of antipsychotic treatment in naïve or quasi-naïve children and adolescents: design of a follow-up protocol. Rev Psiquiatr Salud Ment 2012, 5:217-228.
• [17]San L, Arranz B, Perez V, Safont G, Corripio I, Ramirez N, Dueñas R, Alvarez E: One-year, randomized, open trial comparing olanzapine, quetiapine, risperidone and ziprasidone effectiveness in antipsychotic-naïve patients with a first-episode psychosis. Psychiatry Res 2012, 200:693-701.
• [18]Andersen R, Fagerlund B, Rasmussen H, Ebdrup BH, Aggernaes B, Gade A, Oranje B, Glenthoj B: Cognitive effects of six months of treatment with quetiapine in antipsychotic-naïve first-episode schizophrenia. Psychiatry Res 2011, 187:49-54.
• [19]Raffin M, Gianitelli M, Consoli A, Bonnot O, Menard ML, Askenazy F, Laurent C, Cohen D: Management of adverse effects of second-generation antipsychotics in youth. Curr Treat Options Psychiatr 2014. doi:10.1007/s40501-013-0007-9
• [20]Ben AL: Antipsychotics in pediatric and adolescent patients: a review of comparative safety data. J Affect Disord 2012, 138(Suppl):S22-S30.
• [21]De Hert M, Dobbelaere M, Sheridan EM, Cohen D, Correll CU: Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents: a systematic review of randomized, placebo controlled trials and guidelines for clinical practice. Eur Psychiatry 2011, 26:144-158.
• [22]Bonnot O, Inaoui R, Lloret Linares C, Cohen D: Principes de surveillance des effets métaboliques, de l’hyperprolactinémie et du rythme cardiaque pour les antipsychotiques atypiques chez l’enfant et l’adolescent. Neuropsychiatr Enf Adolesc 2010, 58:431-438.
• [23]Maayan L, Correll CU: Management of antipsychotic-related weight gain. Expert Rev Neurother 2010, 10:1175-1200.
• [24]Morrato E, Nicol GE, Maahs D, Druss BG, Hartung DM, Valuck RJ, Campagna E, Newcommer JW: Metabolic screening in children receiving antipsychotic drug treatment. Arch Pediatr Adolesc Med 2010, 164:344-351.
• [25]Correll CU: Assessing and maximizing the safety and tolerability of antipsychotics used in the treatment of children and adolescents. J Clin Psychiatry 2008, 69(Suppl4):26-36.
• [26]Fleischhaker C, Heiser P, Hennighausen K, Herpertz-Dahlmann B, Holtkamp K, Mehler-Wex C, Rauh R, Remschmidt H, Schulz E, Warnke A: Clinical drug monitoring in child and adolescent psychiatry: side effects of atypical neuroleptics. J Child Adolesc Psychopharmacol 2006, 16:308-316.
• [27]Ho J, Pangiotopoulos C, McCrindle B, Grisaru S, Pringsheim T, and CAMESA guideline group: Management recommendations for metabolic complications associated with second generation antipsychotic use in children and youth. Paediatr Child Health 2011, 16:575-580.
• [28]Pringsheim T, Pangiotopoulos C, Davidson J, Ho J, and CAMESA guideline group: Evidence-based recommendations for monitoring safety of second generation antipsychotics in children and youth. J Can Acad Child Adolesc Psychiatry 2011, 20:218-233.
• [29]Pringsheim T, Doja A, Belanger S, Patten S, CAMESA guideline group: Treatment recommendations for extrapyramidal side effects associated with the second-generation antipsychotic use in child and youth. Paediatr Child Health 2011, 16:590-598.
• [30]Correll CU, Manu P, Olshanskiy V, Napolitano B, Kane JM, Malhotra AK: Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 2009, 302:1765-1773.
• [31]Perez-Iglesias R, Mata I, Pelayo-Teran JM, Amado JA, Garcia-Unzueta MT, Berja A, Martinez-Garcia O, Vazquez-Barquero JL, Crespo-Facorro B: Glucose and lipid disturbances after 1 year of antipsychotic treatment in a drug-naïve population. Schizophr Res 2009, 107:115-121.
• [32]Winterfeld U, le Heuzey MF, Acquaviva E, Mouren MC, Brion F, Bourdon O: Utilisation hors autorisation de mise sur le marché (AMM) des psychotropes en pédiatrie : une étude prospective. Arch Pediatr 2009, 16:1252-1260.
• [33]Pichot P, Overall JE, Samuel-Lajeunesse B, Drefus JF: Structure factorielle de l’échelle abrégée d’appréciation psychiatrique. Rev Psychol Appl 1969, 19:218-232.
• [34]Kay SR, Opler LA, Fiszbein A: Manuel de cotation de la PANSS (1986), traduction française Lépine JP. 1988.
• [35]Lecrubier Y, Boyer P: Fiche descriptive et traduction française de la SANS. Psychiatr Psychobiol 1987, 2:414-423.
• [36]Favre S, Aubry JM, Gex Fabry M, Ragama Pardos E, McQuillan A, Bertschy G: Traduction et validation française de l’échelle de manie de Young (YMRS). Encéphale 2003, 29:499-505.
• [37]Lemperière T, Lépine JP, Rouillon F, Hardy P, Ades J, Luaute JP, Ferrand I: Comparaison de différents instruments d’évaluation de la dépression à l’occasion d’une étude sur l’Athymil 30 mg. Ann Med Psychol 1984, 1984(142):1206-1212.
• [38]Chouinard G, Margolese HC: Manual for the Extrapyramidal Symptom Rating Scale (ESRS). Schizophr Res 2005, 76:247-265.
• [39]Bush G, Fink M, Petrides G, Dowling F, Francis A: Catatonia I: rating scale and standardized examination. Acta Psychiatr Scand 1996, 93:129-136.
• [40]Ratzoni G, Gothelf D, Brand-Gothelf A, Reidman J, Kikinzon L, Gal G, Phillip M, Apter A, Weizman R: Weight gain associated with olanzapine and Risperidone in adolescent patients: a comparative prospective study. J Am Acad Child Adolesc Psychiatry 2002, 41:337-343.
• [41]Menard ML, Askénazy F: Evaluation de l’incidence des événements indésirables sous antipsychotique en population pédiatrique naïve (Etude ETAPE : Etude de la Tolérance des AntiPsychotiques chez l’Enfant). Neuropsychiatr Enf Adolesc 2013, 2013(61):131-132.
• [42]Menard ML, Askénazy F, Auby P, Bonnot O, Cohen D: Sécuriser la prescription des antipsychotiques en population pédiatrique : une étude multicentrique française en population naïve. Encéphale 2013, 39:313-314.
• [43]Assessment of adverse events in a naive pediatric population treated with an antipsychotic [http://clinicaltrials.gov/show/NCT02007928 webcite]
• [44]March JS, Silva SG, Compton S, Anthony G, DeVeaugh-Geiss J, Califf R, Krishnan R: The Child and Adolescent Psychiatry Trials Network (CAPTN). J Am Acad Child Adolesc Psychiatry 2004, 43:515-518.
• [45]Guy W: ECDEU Assessment Manual for Psychopharmacology: Revised (DHEW publication number ADM 76-338). Rockville, MD: US Department of Health, Education and Welfare, Public Health Service, Alcohol, Drug Abuse and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976:534-537.
• [46]Barnes TR: A rating scale for drug-induced Akathisia. Br J Psychiatry 1989, 154:672-676.
• [47]Simpson GM, Angus JW: A rating scale for extra-pyramidal side effects. Acta Psychiatr Scand 1970, 212:11-19.
• [48]Whiteside SP: Adapting the Sheehan disability scale to assess child and parent impairment related to childhood anxiety disorders. J Clin Child Adolesc Psychol 2009, 38:721-730.
• [49]Kermarrec S, Kabuth B, Bursztejn C, Guillemin F: French adaptation and validation of the helping alliance questionnaires for child, parents and therapist. Can J Psychiatry 2003, 51:913-922.
• [50]Johnson WG, Grieve FG, Adams CD, Sandy J: Measuring binge eating in adolescents: adolescent and parent versions of the questionnaire of eating and weight patterns. Int J Eat Disord 1999, 26:301-314.