Therapeutic drug monitoring of sertraline in children and adolescents: A naturalistic study with insights into the clinical response and treatment of obsessive-compulsive disorder

Elvira Tini; Lukasz Smigielski; Marcel Romanos; Christoph Wewetzer; Andreas Karwautz; Karl Reitzle; Christoph U Correll; Paul L Plener; Uwe Malzahn; Peter Heuschmann; Stefan Unterecker; Maike Scherf-Clavel; Hans Rock; Gisela Antony; Wolfgang Briegel; Christian Fleischhaker; Tobias Banaschewski; Tobias Hellenschmidt; Hartmut Imgart; Michael Kaess; Michael Kölch; Tobias Renner; Su-Yin Reuter-Dang; Christian Rexroth; Gerd Schulte-Körne; Frank Theisen; Stefanie Fekete; Regina Taurines; Manfred Gerlach; Karin Maria Egberts; Susanne Walitza

doi:10.1016/j.comppsych.2022.152301

Therapeutic drug monitoring of sertraline in children and adolescents: A naturalistic study with insights into the clinical response and treatment of obsessive-compulsive disorder

Compr Psychiatry. 2022 May:115:152301. doi: 10.1016/j.comppsych.2022.152301. Epub 2022 Feb 26.

Authors

Elvira Tini¹, Lukasz Smigielski², Marcel Romanos³, Christoph Wewetzer⁴, Andreas Karwautz⁵, Karl Reitzle⁶, Christoph U Correll⁷, Paul L Plener⁸, Uwe Malzahn⁹, Peter Heuschmann¹⁰, Stefan Unterecker¹¹, Maike Scherf-Clavel¹¹, Hans Rock¹², Gisela Antony¹², Wolfgang Briegel¹³, Christian Fleischhaker¹⁴, Tobias Banaschewski¹⁵, Tobias Hellenschmidt¹⁶, Hartmut Imgart¹⁷, Michael Kaess¹⁸, Michael Kölch¹⁹, Tobias Renner²⁰, Su-Yin Reuter-Dang²¹, Christian Rexroth²², Gerd Schulte-Körne²³, Frank Theisen²⁴, Stefanie Fekete³, Regina Taurines³, Manfred Gerlach³, Karin Maria Egberts³, Susanne Walitza²⁵

Affiliations

¹ Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zürich, Switzerland. Electronic address: elvira.tini@pukzh.ch.
² Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zürich, Switzerland.
³ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany.
⁴ Kliniken der Stadt Köln GmbH, Clinic for Child and Adolescent Psychiatry Holweide, Children's Hospital Amsterdamer Straße, Cologne, Germany.
⁵ Department of Child and Adolescent Psychiatry, Medical University Vienna, Vienna, Austria.
⁶ Specialist practice and Medical Care Center for Child and Adolescent Psychiatry Munich, Munich, Germany.
⁷ Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany; The Zucker Hillside Hospital, Department of Psychiatry, Northwell Health, Glen Oaks, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Department of Psychiatry and Molecular Medicine, Hempstead, NY, USA.
⁸ Department of Child and Adolescent Psychiatry/Psychotherapy, University Hospital Ulm, Ulm, Germany; Department of Child and Adolescent Psychiatry, Medical University Vienna, Vienna, Austria.
⁹ Clinical Trial Center Wuerzburg, University Hospital Wuerzburg, Wuerzburg, Germany.
¹⁰ Clinical Trial Center Wuerzburg, University Hospital Wuerzburg, Wuerzburg, Germany; Institute of Clinical Epidemiology and Biometry, University of Wuerzburg, Germany.
¹¹ Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany.
¹² Central Information Office, Department of Neurology, Philipps University of Marburg, Marburg, Germany.
¹³ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany; Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Leopoldina Hospital, Schweinfurt, Germany.
¹⁴ Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany.
¹⁵ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
¹⁶ Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatic medicine, Vivantes Clinic Berlin Neukölln, Berlin, Germany.
¹⁷ Parkland-Clinic, Clinic for Psychosomatics and Psychotherapy, Academic Teaching Hospital for the University Gießen, Bad Wildungen, Germany.
¹⁸ Clinic for Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany; University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.
¹⁹ Department of Child and Adolescent Psychiatry and Psychotherapy, Brandenburg Medical School Brandenburg, Neuruppin, Germany; Department of Child and Adolescent Psychiatry, Neurology, Psychosomatics, and Psychotherapy, University Medical Center Rostock, Rostock, Germany.
²⁰ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Psychiatry and Psychotherapy Tuebingen, Center of Mental Health Tuebingen, Germany.
²¹ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany; Specialist practice and Medical Care Center for Child and Adolescent Psychiatry Munich, Munich, Germany.
²² Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Regensburg at the Regensburg District Hospital, Medbo KU, Regensburg, Germany.
²³ Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-University (LMU) Hospital, Munich, Germany.
²⁴ Department of Child and Adolescent Psychiatry and Psychotherapy, Herz-Jesu-Krankenhaus gGmbH, Fulda, Germany.
²⁵ Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zürich, Switzerland; Zurich Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland.; Neuroscience Center Zurich, University of Zurich and ETH, Zurich, Switzerland.. Electronic address: susanne.walitza@pukzh.ch.

PMID: 35248877
DOI: 10.1016/j.comppsych.2022.152301

Abstract

Background: Sertraline is a selective serotonin reuptake inhibitor with specific indications in child and adolescent psychiatry. Notwithstanding its frequent use and clinical benefits, the relationship between pharmacokinetics, pharmacodynamics, efficacy, and tolerability of sertraline across indications, particularly in non-adult patients, is not fully understood.

Method: This naturalistic therapeutic drug monitoring (TDM) study was conducted in a transdiagnostic sample of children and adolescents treated with sertraline (n = 78; mean age, 14.22 ± 2.39; range, 7-18 years) within the prospective multicenter "TDM-VIGIL" project. Associations between dose, serum concentration, and medication-specific therapeutic and side effects based on the Clinical Global Impression scale were examined. Tolerability was measured qualitatively with the 56-item Pediatric Adverse Event Rating Scale.

Results: A strong linear positive dose-serum concentration relationship (with dose explaining 45% of the variance in concentration) and significant effects of weight and co-medication were found. Neither dose nor serum concentration were associated with side effects. An overall mild-to-moderate tolerability profile of sertraline was observed. In contrast with the transdiagnostic analysis that did not indicate an effect of concentration, when split into depression (MDD) and obsessive-compulsive disorder (OCD) diagnoses, the probability of clinical improvement significantly increased as both dose and concentration increased for OCD, but not for MDD.

Conclusions: This TDM-flexible-dose study revealed a significant diagnosis-specific effect between sertraline serum concentration and clinical efficacy for pediatric OCD. While TDM already guides clinical decision-making regarding compliance, dose calibration, and drug-drug interactions, combining TDM with other methods, such as pharmacogenetics, may facilitate a personalized medicine approach in psychiatry.

Keywords: TDM; antidepressants; pharmacovigilance; selective serotonin reuptake inhibitors; steady state concentration.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Child
Drug Monitoring / methods
Humans
Obsessive-Compulsive Disorder* / diagnosis
Obsessive-Compulsive Disorder* / drug therapy
Prospective Studies
Selective Serotonin Reuptake Inhibitors / therapeutic use
Sertraline* / therapeutic use

Substances

Serotonin Uptake Inhibitors
Sertraline