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Pharmakovigilanz in der Kinder- und Jugendpsychiatrie

Published Online:https://doi.org/10.1024/1422-4917/a000329

Die rationale Therapie mit Arzneimitteln stellt eine Herausforderung in der Kinder- und Jugendpsychiatrie dar. Steigende Verordnungszahlen stehen im Kontrast zu erheblichen Unsicherheiten in Bezug auf die Arzneimittelsicherheit und Wirksamkeit. Der Mangel an (Zulassungs-)Studien führt häufig zu einem nicht altersspezifischen Gebrauch der Medikamente. Junge Patienten weisen jedoch besondere Stoffwechselbedingungen sowie eine höhere Vulnerabilität für unerwünschte Arzneimittelwirkungen (UAW) auf. Es ist daher notwendig, eigene Daten zur Pharmakokinetik, Wirkung und Sicherheit von Psychopharmaka bei Minderjährigen zu generieren. Auch die Gesetzgebung hat diese Situation erkannt und auf nationaler sowie europäischer Ebene entsprechende Vorschriften sowie wissenschaftliche Programme eingeführt. Ziel der unter dem Begriff der Pharmakovigilanz zusammengefassten Maßnahmen ist es, das Nutzen-Risiko-Verhältnis eines Arzneimittels kontinuierlich zu evaluieren, UAWs so schnell wie möglich zu entdecken und deren Risiken durch geeignete Maßnahmen, z. B. konsequentes Therapeutisches Drug Monitoring (TDM), zu minimieren. Der folgende Artikel erläutert die Notwendigkeit sowie Grundlagen der Pharmakovigilanz in der Kinder- und Jugendpsychiatrie und stellt ein vom Bundesministerium für Arzneimittel und Medizinprodukte (BfArM) gefördertes multizentrisches epidemiologisches Forschungsprojekt («TDM-VIGIL») vor, an dem zahlreiche kinder- und jugendpsychiatrische Zentren sowie Facharztpraxen aus dem deutschsprachigen Raum beteiligt sind. Ziel ist die systematischen Erfassung von Informationen zum Verordnungsverhalten und der Sicherheit von Psychopharmaka im Kindes- und Jugendalter mittels eines internetbasierten Patientenregisters.


Pharmacovigilance in Child and Adolescent Psychiatry

Rational pharmacotherapy is a challenging task in child and adolescent psychiatry. Increasing prescription numbers contrast with the uncertainties of safety and efficacy issues. The lack of clinical (authorization) trials often implies a non- age-specific use of drugs. However, young patients show particular metabolic conditions and a higher vulnerability for adverse drug reactions. Thus it seems mandatory to create age-specific pharmacological data about efficacy and safety of psychotropic drug use in minors. Legislation authorities became aware of this situation and introduced European and national scientific pharmacovigilance regulations and programmes accordingly in order to continuously evaluate the benefit-risk-ratio, detect, collect, minimize, and prevent adverse effects of drugs by appropriate measures, e.g., therapeutic drug monitoring. In this paper the principles and needs of pharmacovigilance in child and adolescent psychiatry are discussed. Furthermore a large multicenter clinical trial («TDM-VIGIL»), funded by the German Federal Institute for Drugs and Medical Devices, is presented, which appeals to collect epidemiological prescription and safety data of psychotropic drugs in children and adolescents using an internet-based data infrastructure (patient registry).

Literatur

  • American Psychiatric Association . (2000). Diagnostic and statistical manual of mental disorders. Text revision (4th ed., DSM-IV-TR). Washington DC: American Psychiatric Association. First citation in articleGoogle Scholar

  • Arzneimittelkommission der deutschen Ärzteschaft. (Hrsg.). (2005). Sonderheft Pharmakovigilanz. AVP (Arzneiverordnung in der Praxis), Berlin 32, 1–30. First citation in articleGoogle Scholar

  • Baumann, P. , Hiemke, C. , Ulrich, S. , Eckermann, G. , Gaertner, I. , Gerlach, M. , Zernig, G. (2004). Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie. The AGNP-TDM expert group consensus guidelines: Therapeutic drug monitoring in psychiatry. Pharmacopsychiatry, 37, 243–265. First citation in articleCrossref MedlineGoogle Scholar

  • Breitkreutz, J. (2008). European perspectives on pediatric formulations. Clinical Therapeutics, 30, 2146–2154. First citation in articleCrossref MedlineGoogle Scholar

  • Classen, D. C. , Pestotnik, S. L. , Evans, R. S. , Lloyd, J. F. , Burke, J. P. (1997). Adverse drug events in hospitalized patients. Excess length of stay, extra costs, and attributable mortality. Journal of the American Medical Association, 277, 301–306. First citation in articleCrossrefGoogle Scholar

  • Couchman, L. , Bowskill, S. , Handley, S. , Patel, M. , Flanagan, R. (2013). Plasma clozapine and norclozapine in relation to prescribed dose and other factors in patients aged <18 years: Data from a therapeutic drug monitoring service, 1994–2010. Early Intervention in Psychiatry, 7, 122–130. First citation in articleCrossrefGoogle Scholar

  • Duijnhoven, R. G. , Straus, S. M. , Raine, J. M. , de Boer, A. , Hoes, A. W. , De Bruin, M. L. (2013). Number of patients studied prior to approval of new medicines: A database analysis. PLoS Medicine, 10(3), e1001407. First citation in articleGoogle Scholar

  • Egberts, T. C. G. , Smulders, M. , de Koning, F. H. , Meyboom, R. H. , Leufkens, H. G. (1996). Can adverse drug reactions be detected earlier? A comparison of reports by patients and professionals. British Medical Journal, 313(7056), 530–531. First citation in articleCrossref MedlineGoogle Scholar

  • Egberts, K. M. , Mehler-Wex, C. , Gerlach, M. (2011). Therapeutic drug monitoring in child and adolescent psychiatry. Pharmacopsychiatry, 44, 249–253. First citation in articleCrossref MedlineGoogle Scholar

  • EMA Paediatric Committee . (2012). EMA 428172/2012: 5-year report to the European Commission. Prepared by the European Medicines Agency (eu.europa.eu/health/files/paediatrics/ 2012-09_pediatri_-report-annex-1-2_eu.pdf). First citation in articleGoogle Scholar

  • Fegert, J. M. , Kölch, M. , Lippert, H. D. , Oehler, K.-U. und die Mitglieder der Kommission Entwicklungspsychopharmakologie . (2009). Stellungnahme der Kommission Entwicklungspharmakologie zum Off-label use. Forum für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie, 2, 99– 109. First citation in articleGoogle Scholar

  • Gerlach, M. , Hünnerkopf, R. , Rothenhöfer, S. , Libal, G. , Burger, R. , Clement, H.-W. , Mehler-Wex, C. (2007). Therapeutic drug monitoring of quetiapine in adolescents with psychotic disorders. Pharmacopsychiatry, 40, 72–76. First citation in articleCrossref MedlineGoogle Scholar

  • Gyllensten, H. , Rehnberg, C. , Jönsson, A. K. , Petzold, M. , Carlsten, A. , Andersson Sundell, K. (2013). Cost of illness of patient-reported adverse drug events: a population-based cross-sectional survey. British Medical Journal Open, Jun 20, 3(6), e002574. First citation in articleGoogle Scholar

  • Harrison, J. N. , Cluxton-Keller, F. , Gross, D. (2012). Antipsychotic medication prescribing trends in children and adolescents. Journal of Pediatric Health Care, 26, 139–145. First citation in articleCrossref MedlineGoogle Scholar

  • Herxheimer, A. , Crombag, M. R. , Alves, T. L. (2010). Health Action International (HAI) Europe: Direct patient reporting of adverse drug reactions: A twelve-country survey & literature review. Retrieved from www.haiweb.org/14012010/14Jan2010ReportDirectPatientReportingofADRsFINAL.pdf. First citation in articleGoogle Scholar

  • Hiemke, C. , Baumann, P. , Bergemann, N. , Conca, A. , Dietmaier, O. , Egberts, K. , Zernig, G. (2011). AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: Update 2011. Pharmacopsychiatry, 44, 195–235. First citation in articleCrossrefGoogle Scholar

  • Karwautz, A. , Bangratz, S. , Huemer, J. (2011). Qualitätssicherung in der kinder- und jugendpsychiatrischen Psychopharmakotherapie – Einsatz von Therapeutic Drug Monitoring. Pädiatrie & Pädologie, 2, 10–12. First citation in articleCrossrefGoogle Scholar

  • Klampfl, K. , Taurines, R. , Preuss, A. , Burger, R. , Rothernhöfer, S. , Wewetzer, C. , Mehler-Wex, C. (2010b). Serum concentrations, therapeutic response and side effects in children and adolescents with impulsive-aggressive symptoms during risperidone therapy. Pharmacopsychiatry, 43, 58–65. First citation in articleCrossref MedlineGoogle Scholar

  • Klampfl, K. , Mehler-Wex, C. , Warnke, A. , Gerlach, M. (2010a). Therapeutisches Drug-Monitoring in der Kinder- und Jugendpsychiatrie. Psychopharmakotherapie, 17, 193–200. First citation in articleGoogle Scholar

  • Koelch, M. , Prestel, A. , Singer, H. , Keller, F. , Fegert, J. M. , Schlack, R. , Knopf, H. (2009). Psychotropic medication in children and adolescents in Germany: Prevalence, indications, and psychopathological patterns. Journal of Child and Adolescent Psychopharmacology, 19, 765–770. First citation in articleCrossref MedlineGoogle Scholar

  • Koelch, M. , Pfalzer, A.-K. , Kliegl, K. , Rothenhöfer, S. , Ludolph, A. , Fegert, J. , Gerlach, M. (2012). Therapeutic drug monitoring of children and adolescents treated with fluoxetine. Pharmacopsychiatry, 45, 72–76. First citation in articleCrossref MedlineGoogle Scholar

  • Lasser, K. E. , Allen, P. D. , Woolhandler, S. J. , Himmelstein, D. U. , Wolfe, S. M. , Bor, D. H. (2002). Timing of new black box warnings and withdrawals for prescription medications. Journal of the American Medical Association, 287, 2215–2220. First citation in articleCrossrefGoogle Scholar

  • Lehmkuhl, G. , Schubert, I. (2014). Psychotropic medication in children and adolescents. Deutsches Ärzteblatt International, 111, 23–24. First citation in articleGoogle Scholar

  • National Institute of Mental Health . (1970). CGI: Clinical global impression. In W. Guy, R. R. Bonato (Eds.), Manual for the ECDEU Assessment Battery (2nd ed.). Bethesda, MD: Autor. First citation in articleGoogle Scholar

  • Olski, T. M. , Lampus, S. F. , Gherarducci, G. , Saint Raaymond, A. (2011). Three years of paediatric regulation in the European Union. European Journal of Clinical Pharmacology, 67, 245–252. First citation in articleCrossref MedlineGoogle Scholar

  • Rodríguez-Monguió, R. , Otero, M. J. , Rovira, J. (2003). Assessing the economic impact of adverse drug effects. Pharmacoeconomics, 21, 623–650. First citation in articleCrossref MedlineGoogle Scholar

  • Sammons, H. M. , Gray, C. , Hudson, H. , Cherrill, J. , Choonara, I. (2008). Safety in paediatric clinical trial – A 7-year review. Acta Paediatrica, 97, 474–477. First citation in articleCrossref MedlineGoogle Scholar

  • Taurines, R. , Burger, R. , Wewetzer, C. , Pfuhlmann, B. , Mehler-Wex, C. , Gerlach, M. , Egberts, K. (2013). The relation between dosage, serum concentrations and clinical outcome in children and adolescents treated with sertraline: A naturalistic study. Therapeutic Drug Monitoring, 35, 84–91. First citation in articleCrossref MedlineGoogle Scholar

  • Thomann, K. D. (2007). Die Contergan-Katastrophe: Die trügerische Sicherheit der «harten» Daten. Deutsches Ärzteblatt, 104, A-2778. First citation in articleGoogle Scholar

  • Van Riet-Nales, D. A. , de Jager, K. E. , Schobben, A. F. , Egberts, T. C. , Rademaker, C. M. (2010). The availability and age-appropriateness of medicines authorized for children in The Netherlands. British Journal of Clinical Pharmacology, 72, 465–473. First citation in articleCrossrefGoogle Scholar

  • Van Riet-Nales, D. , Wang, S. , Saint-Raymond, A. , Robert, J.-L. (2012). The EMa quality guideline on the pharmaceutical development of medicines for paediatric use. International Journal of Pharmaceutics, 435, 132–134. First citation in articleCrossref MedlineGoogle Scholar

  • Yuill, K. , Carandang, C. (2013). Safety methodology in pediatric psychopharmacology trials. Journal of Child and Adolescent Psychopharmacology, 23, 148–162. First citation in articleCrossref MedlineGoogle Scholar

  • Zito, J. M. , Derivan, A. T. , Kratochvil, C. , Safer, D. J. , Fegert, J. , Greenhill, L. (2008). Off-label psychopharmacologic prescribing for children: History supports close clinical monitoring. Child and Adolescent Psychiatry and Mental Health, 2, 24. First citation in articleCrossref MedlineGoogle Scholar