Pharmacopsychiatry 2017; 50(06): 248-255
DOI: 10.1055/s-0043-109695
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Relationship Between Daily Dose, Serum Concentration, and Clinical Response to Quetiapine in Children and Adolescents with Psychotic and Mood Disorders

Laura Albantakis*
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health,Würzburg, Germany,
,
Karin Egberts
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health,Würzburg, Germany,
,
Rainer Burger
2   Department of Psychiatry, Psychosomatics and Psychotherapy,University Hospital of Würzburg, Centre for Mental Health, Würzburg, Germany
,
Christine Kulpok
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health,Würzburg, Germany,
,
Claudia Mehler-Wex
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health,Würzburg, Germany,
3   HEMERA Private Hospital for Mental Health, Adolescents and Young Adults, Bad Kissingen, Germany
4   Affiliation between January 2007 and December 2008: University Hospital of Ulm, Department of Child and Adolescent Psychiatry and Psychotherapy, Ulm, Germany
,
Regina Taurines
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health,Würzburg, Germany,
,
Stefan Unterecker
2   Department of Psychiatry, Psychosomatics and Psychotherapy,University Hospital of Würzburg, Centre for Mental Health, Würzburg, Germany
,
Christoph Wewetzer
5   Clinics of the City Cologne GmbH, Clinic for Child and Adolescent Psychiatry and Psychotherapy, Cologne, Germany
,
Marcel Romanos
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health,Würzburg, Germany,
,
Manfred Gerlach
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Centre for Mental Health,Würzburg, Germany,
› Author Affiliations
Further Information

Publication History

received 03 August 2016
revised 17 April 2017

accepted 19 April 2017

Publication Date:
23 May 2017 (online)

Abstract

Introduction In child and adolescent psychiatry, therapeutic drug monitoring (TDM) is strongly recommended. However, therapeutic ranges (TR) are defined only for adults. The objectives of this naturalistic study were to assess the relationships between serum quetiapine concentration, daily dose, and clinical outcomes as well as the determinants of pharmacokinetic variability. Furthermore, it was elucidated whether the recommended TR for adult patients with psychotic disorders is valid for children and adolescents.

Methods TDM was performed in 180 pediatric patients treated with quetiapine. Psychopathological changes were assessed by the Clinical Global Impression – Improvement scale (CGI-I). Adverse drug reactions (ADRs) were assessed by using a short form of the Udvalg for Kliniske Undersogelser (UKU) side effect rating scale.

Results A weak positive linear relationship between daily dose (mean 349.9±248.9 mg/day) and serum concentration of quetiapine (rs=0.496, p<0.001) was found (mean age 15.6±1.9 years, 45.6% male, 31.1% monotherapy), but no relationship between serum concentration and clinical outcome was found. Dose variation accounted for only 12.5% (rs 2=0.125) of the variability of serum concentrations. No effects by gender, age, body weight, smoking habits, and co-medication were found. The majority of patients with psychotic (67.8%) and mood disorders (74.5%) showed a serum concentration below the suggested lower limit (100 ng/mL) of the TR for adults.

Discussion There are several limitations of this study because of the naturalistic design, and our results should therefore be interpreted with caution. Notwithstanding, our data suggest that the lower limit of the TR for quetiapine is lower than the limit in adult patients.

* Current address: Max Planck Institute of Psychiatry, Kraepelinstraße 2-10, 80804 München


 
  • References

  • 1 Schimmelmann BG, Mehler-Wex C, Wewetzer Ch. Schizophrenia. In: Gerlach M, Warnke A, Greenhill L. eds. Psychiatric drugs in children and adolescents. Vienna: Springer; 2014: 499-506
  • 2 Rothenhöfer S, Warnke A. Wewetzer Ch. Manic episode and bipolar affective disorder. In: Gerlach M, Warnke A, Greenhill L. eds. Psychiatric drugs in children and adolescents. Vienna: Springer; 2014: 459-468
  • 3 Gerlach M, Mehler-Wex C, Schimmelmann BG. Antipsychotics. In: Gerlach M, Warnke A, Greenhill L. eds. Psychiatric drugs in children and adolescents. Vienna: Springer; 2014: 157-218
  • 4 Gerlach M, Greenhill L, Warnke A. Special features of psychopharmacological therapy in children and adolescents. In: Gerlach M, Warnke A, Greenhill L. eds. Psychiatric drugs in children and adolescents. Vienna: Springer; 2014: 61-75
  • 5 Egberts KM, Karwautz A, Plener PL. et al. Pharmacovigilance in child and adolescent psychiatry. Z Kinder Jugendpsychiatr Psychother 2015; 43: 21-28
  • 6 Gerlach M, Egberts K, Dang SY. et al. Therapeutic drug monitoring as a measure of proactive pharmacovigilance in child and adolescent psychiatry. Exp Opin Drug Saf 2016; 15: 1477-1482
  • 7 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
  • 8 Egberts KM, Mehler-Wex C, Gerlach M. Therapeutic drug monitoring in child and adolescent psychiatry. Pharmacopsychiatry 2011; 44: 249-253
  • 9 Hiemke C, Baumann P, Bergemann N. et al. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: Update 2011. Pharmacopsychiatry 2011; 44: 195-235
  • 10 Gerlach M, Hünnerkopf R, Rothenhöfer S. et al. Therapeutic drug monitoring of quetiapine in adolescents with psychotic disorders. Pharmacopsychiatry 2007; 40: 72-76
  • 11 Kirschbaum KM, Finger S, Vogel F. et al. High performance-liquid chromatography with column-switching and spectrophotometric detection for determination of risperidone and 9-hydroxyrisperidone in human serum. Chromatographia 2008; 67: 321-324
  • 12 Wohkittel C, Gerlach M, Taurines R. et al. Relationship between clozapine dose, serum concentration, and clinical outcome in children and adolescents in clinical practice. J Neural Transm (Vienna) 2016; 123: 1021-1031
  • 13 Figueroa C, Brecher M, Hamer-Maansson JE. et al. Pharmacokinetic profiles of extended release quetiapine fumarate compared with quetiapine immediate release. Prog Neuropsychopharmacol Biol Psychiatry. 2009; 33: 199-204
  • 14 Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgemont) 2007; 4: 28-37
  • 15 Lingjaerde O, Ahlfors UG, Bech P. et al. The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand Suppl 1987; 334: 1-100
  • 16 Sparshatt A, Taylor D, Patel MX. et al. Relationship between daily dose, plasma concentrations, dopamine receptor occupancy, and clinical response to quetiapine: A review. J Clin Psychiatry 2011; 72: 1108-1123
  • 17 Castberg I, Skogvoll E, Spigset O. Quetiapine and drug interactions: evidence from a routine therapeutic drug monitoring service. J Clin Psychiatry 2007; 68: 1540-1545
  • 18 Winter HR, Earley WR, Hamer-Maansson JE. et al. Steady-state pharmacokinetic, safety, and tolerability profiles of quetiapine, norquetiapine, and other quetiapine metabolites in pediatric and adult patients with psychotic disorders. J Child Adolesc Psychopharmacol 2008; 18: 81-98
  • 19 Aichorn W, Marksteiner J, Walch T. Influence of age, gender, body weight and valproate comedication on quetiapine plasma concentrations. Int Clin Psychopharmacol 2006; 21: 81-85
  • 20 Vella T, Mifsud J. Interactions between valproic acid and quetiapine/olanzapine in the treatment of bipolar disorder and the role of therapeutic drug monitoring. J Pharm Pharmacol 2014; 66: 747-759
  • 21 Preskorn SH. Therapeutic Drug Monitoring (TDM) in psychiatry (part I): why studies attempting to correlate drug concentration and antidepressant response don't work. J Psychiatr Pract 2014; 20: 133-137
  • 22 Castberg I, Spigset O. Prescribing patterns and the use of therapeutic drug monitoring of psychotropic medication in a psychiatric high-security unit. Ther Drug Monit 2008; 30: 597-603