Comprehensive Psychiatry (May 2022)
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
Affiliations
- Elvira Tini
- Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zürich, Switzerland; Corresponding authors at: Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University Zurich, Switzerland.
- Lukasz Smigielski
- Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zürich, Switzerland
- Marcel Romanos
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany
- Christoph Wewetzer
- Kliniken der Stadt Köln GmbH, Clinic for Child and Adolescent Psychiatry Holweide, Children's Hospital Amsterdamer Straße, Cologne, Germany
- Andreas Karwautz
- Department of Child and Adolescent Psychiatry, Medical University Vienna, Vienna, Austria
- Karl Reitzle
- Specialist practice and Medical Care Center for Child and Adolescent Psychiatry Munich, Munich, Germany
- Christoph U. Correll
- 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
- Paul L. Plener
- Department of Child and Adolescent Psychiatry/Psychotherapy, University Hospital Ulm, Ulm, Germany; Department of Child and Adolescent Psychiatry, Medical University Vienna, Vienna, Austria
- Uwe Malzahn
- Clinical Trial Center Wuerzburg, University Hospital Wuerzburg, Wuerzburg, Germany
- Peter Heuschmann
- Clinical Trial Center Wuerzburg, University Hospital Wuerzburg, Wuerzburg, Germany; Institute of Clinical Epidemiology and Biometry, University of Wuerzburg, Germany
- Stefan Unterecker
- Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
- Maike Scherf-Clavel
- Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
- Hans Rock
- Central Information Office, Department of Neurology, Philipps University of Marburg, Marburg, Germany
- Gisela Antony
- Central Information Office, Department of Neurology, Philipps University of Marburg, Marburg, Germany
- Wolfgang Briegel
- 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
- Christian Fleischhaker
- Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany
- Tobias Banaschewski
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- Tobias Hellenschmidt
- Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatic medicine, Vivantes Clinic Berlin Neukölln, Berlin, Germany
- Hartmut Imgart
- Parkland-Clinic, Clinic for Psychosomatics and Psychotherapy, Academic Teaching Hospital for the University Gießen, Bad Wildungen, Germany
- Michael Kaess
- 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
- Michael Kölch
- 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
- Tobias Renner
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Psychiatry and Psychotherapy Tuebingen, Center of Mental Health Tuebingen, Germany
- Su-Yin Reuter-Dang
- 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
- Christian Rexroth
- Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Regensburg at the Regensburg District Hospital, Medbo KU, Regensburg, Germany
- Gerd Schulte-Körne
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-University (LMU) Hospital, Munich, Germany
- Frank Theisen
- Department of Child and Adolescent Psychiatry and Psychotherapy, Herz-Jesu-Krankenhaus gGmbH, Fulda, Germany
- Stefanie Fekete
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany
- Regina Taurines
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany
- Manfred Gerlach
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany
- Karin Maria Egberts
- Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany
- Susanne Walitza
- 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.; Corresponding authors at: Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University Zurich, Switzerland.
- Journal volume & issue
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Vol. 115
p. 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.
