Therapeutic Drug Monitoring in Child and Adolescent Psychiatry^[*]

Abstract

Psychopharmacotherapy in children and adolescents is characterized by an increased susceptibility for adverse events and an increased risk of ineffective treatment due to specific age-dependent and developmental characteristics in comparison to adults. Dosing in paediatric psychiatric patients requires careful handling, since the dose recommendations for adults can not simply be extrapolated to minors because of pharmacokinetic and pharmacodynamic differences. In addition, psychopharmacotherapy in children and adolescents is hampered by lack of high quality evidence on efficacy and safety in many indications and subsequently a high degree of off-label use. Therapeutic Drug Monitoring (TDM) is an established and useful tool in psychiatry to individualize and optimize the outcomes (efficacy/safety balance) of psychopharmacological drug treatment in the individual patient by dose adjustments based upon measured serum concentrations. In children and adolescents the administration of psychotropic drugs is a general indication for performing TDM. However, TDM studies specific in these age groups are necessary to identify age and indication specific therapeutic ranges of serum concentrations. Systematic collection of data on drug exposure, serum concentrations and clinical characteristics as well as outcomes can generate such practice-based evidence. A German-Swiss-Austrian competence network for TDM in child and adolescent psychiatry using a multi-centre internet-based data infrastructure was founded to document and collect demographic, safety and efficacy data as well as blood concentrations of psychotropic drugs in children and adolescents (further information: www.tdm-kjp.com).

Key words

therapeutic drug monitoring - child and adolescent psychiatry - psychopharmacotherapy - developmental psychopharmacology

^*

^* Parts of this paper are based on the article „Therapeutisches Drug Monitoring in der Kinder- und Jugendpsychiarie” [18] as well as on “Drug monitoring in child and adolescent psychiatry for improved efficacy and safety of psychopharmacotherapy” [22].

• References

• 1 Aichhorn W, Marksteiner J, Walch T et al. Age and Gender Effects on Olanzapine and Risperidone Plasma Concentrations in Children and Adolescents. J Child Adolesc Psychopharmacol 2007; 17: 665-673
• 2 Bachmann C, Haberhausen M, Heinzel-Gutenbrunner M et al. Large intraindividual variability of Olanzapine serum concentrations in adolescent patients. Ther Drug Monit 2008; 30: 108-112
• 3 Bachmann C, Rieger-Gies A, Heinzel-Gutenbrunner M. Large variability of aripiprazole and hydroaripiprzole serum concentrations in adolescent patients with schizophrenia. Ther Drug Monit 2008; 30: 462-466
• 4 Baumann P, Hiemke C Ulrich et al. The AGNP-TDM expert group consensus guidelines: Therapeutic drug monitoring in Psychiatry. Pharmacopsychiatry 2004; 37: 243-65
• 5 Child and Adolescent Psychiatry Trials Network [ www.captn.org ]
• 6 Correll CU, Manu P, Olshanskiy V et al. Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 2009; 28: 1765-1773 Erratum in: JAMA 2009; 302: 2322
• 7 Findling R, Reed M, Myers C et al. Paroxetine Pharmacokinetics in depressed chidren and adolescents. J Am Acad Child Adolesc Psychiatry 1999; 38: 952-959
• 8 Fleischhaker C, Heiser P, Hennighausen K et al. Weight gain in children and adolescents during 45 weeks treatment with clozapine, olanzapine and risperidone. J Neural Transm 2008; 115: 1599-1608
• 9 Gerlach M, Hünnerkopf R, Rothenhöfer S et al. Therapeutic drug monitoring of quetiapine in adolescents with psychotic disorders. Pharmacopsychiatry 2007; 40: 72-76
• 10 Gerlach M, Klampfl K, Mehler-Wex C et al. Besonderheiten in der Therapie mit Neuro- Psychopharmaka im Kindes- und Jugendalter. In Gerlach M, Mehler-Wex C, Walitza S, Warnke A, Wewetzer C. editors. Neuro- Psychopharmaka im Kindes- und Jugendalter. Grundlagen und Therapie. Wien, New York: Springer-Verlag; 2009. 73-89
• 11 Gerlach M, Klampfl K, Warnke A et al. Besonderheiten der Therapie mit Neuro-Psychopharmaka im Kindes- und Jugendalter, Arzneimitteltherapie psychischer und neurologischer Erkrankungen. Psychopharmakotherapie 2010; 17: 118-125
• 12 Gerlach M, Rothenhöfer S, Mehler-Wex C et al. Therapeutisches Drug-Monitoring in der Kinder- und Jugendpsychiatrie – Grundlagen und praktische Empfehlungen. Z Kinder-Jugendpsychiatr 2006; 34: 5-13
• 13 Gerlach M, Schulz E, Fegert JM. Editorial „Therapeutisches Drug-Monitoring“, eine Strategie zur Verbesserung der Arzneimittelsicherheit in der Kinder- und Jugendpsychiatrie und Psychotherapie. Z Kinder-Jugendpsychiatr 2005; 33: 157-158
• 14 Gerlach M, Warnke A. Allgemeine Aspekte und Besonderheiten der Neuropsychopharmakologie im Kindes- und Jugendalter. In Gerlach M, Warnke A, Wewetzer C. editors. Neuro-Psychopharmaka im Kindes- und Jugendalter. Grundlagen und Therapie. Wien: Springer; 2004. 51-60
• 15 Gerlach M, Wewetzer C. Entwicklungspsychopharmakologie. In Herpertz-Dahlmann B, Resch F, Schulte-Markwort M, Warnke A. editors. Entwicklungspsychiatrie. Biopsychologische Grundlagen und die Entwicklung psychischer Störungen. 2. vollständig überarbeitete und erweiterte Auflage. Stuttgart: Schattauer; 2008. 372-407
• 16 Giedd N, Blumenthal J, Jeffries NO et al. Brain development during childhood and adolescence: a longitudinal MRI study. Nature Neuroscience 1999; 2: 861-863
• 17 Hiemke C, Baumann P, Laux G et al. Therapeutisches Drug Monitoring in der Psychiatrie. Konsensus-Leitlinie der AGNP. Psychopharmakotherapie 2005; 12: 166-182
• 18 Klampfl K, Mehler-Wex C, Warnke A et al. Therapeutisches Drug- Monitoring in der Kinder- und Jugendpsychiatrie. . Psychopharmakotherapie 2010; 17: 193-200
• 19 Klampfl K, Taurines R, Preuss A et al. Serum concentrations, therapeutic response and side effects in children and adolescents with impulsive-aggressive symptoms during risperidone therapy. Pharmacopsychiatry 2010; 43: 58-65
• 20 March J, Karayal O, Chrisman A. CAPTN: The Paediatric Adverse Event Rating Scale. In Novins DK, DeYoung editors. The Scientific Proceedings of the 2007 Annual Meeting of the American Academy of Child and Adolescent Psychiatr. Boston: 2007
• 21 Meesters RJ, van Kampen JJ, Reedijk ML et al. Ultrafast and high-throughput mass spectrometric assay for therapeutic drug monitoring of antiretroviral drugs in pediatric HIV-1 infection applying dried blood spots. Anal Bioanal Chem 2010; 398: 319-328
• 22 Mehler-Wex C, Kölch M, Kirchheiner J et al. Drug monitoring in child and adolescent psychiatry for improved efficacy and safety of psychopharmacotherapy. Child Adolesc Psychiatry Ment Health 2009; 3: 14
• 23 Pichini S, Papaseit E, Joya X et al. Pharmacokinetics and therapeutic drug monitoring of psychotropic drugs in pediatrics. Ther Drug Monit 2009; 31: 283-318
• 24 Poznanski EO, Mokros HB. Children’s depression rating scale, revised (CDRS-R). Los Angeles: Western Psychological Services; 1996
• 25 Rapp PR, Bachevalier J. Cognitive development and aging. In Squire LR, Bloom FE, McConnell SK, Roberts JL, Spitzer NC, Zigmond M. editors. Fundamental Neuroscience. London: Academic Press; 2003. 1167-1200
• 26 Reis M, Olsson G, Carlsson B et al. Serum Levels of Citalopram and its main metabolites in adolescent patients treated in a naturalistic clinical setting. J Clinical Psychopharmacol 2002; 22: 406-413
• 27 Safer DJ, Zito JM. Treatment-Emergent Adverse Events from Selective Serotonin Reuptake Inhibitors by Age Group: Children versus Adolescents. Journal of Child and Adolescent Psychopharmacology 2006; 16: 159-169
• 28 Seeman P, Bzowej NH, Guan H-C et al. Human brain dopamine receptors in children and aging adults. Synapse 1987; 1: 399-404
• 29 Smink BE, Hofman BJ, Dijkhuizen A et al. The concentration of oxazepam and oxazepam glucuronide in oral fluid, blood and serum after controlled administration of 15 and 30 mg oxazepam. Br J Clin Pharmacol 2008; 66: 556-560
• 30 van Riet-Nales DA, Schobben AF, Egberts TC et al. Effects of the pharmaceutical technologic aspects of oral pediatric drugs on patient-related outcomes: a systematic literature review. Clin Ther 2010; 32: 924-938
• 31 Vitiello B. Research in child and adolescent psychopharmacology: recent accomplishments and new challenges. Psychopharmacology 2007; 191: 5-13