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CC BY-NC-ND 4.0 · Pharmacopsychiatry 2022; 55(05): 255-265
DOI: 10.1055/a-1716-1856
Original Paper

Serious Adverse Drug Reactions in Children and Adolescents Treated On- and Off-Label with Antidepressants and Antipsychotics in Clinical Practice

Karin M. Egberts
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
,
Manfred Gerlach
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
,
Christoph U. Correll
2   Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany
3   The Zucker Hillside Hospital, Department of Psychiatry, Northwell Health, Glen Oaks, NY, USA
4   Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Department of Psychiatry and Molecular Medicine, Hempstead, NY, USA
,
Paul L. Plener
5   Department of Child and Adolescent Psychiatry/Psychotherapy, University Hospital Ulm, Ulm, Germany
6   Department of Child and Adolescent Psychiatry, Medical University Vienna, Vienna, Austria
,
Uwe Malzahn
7   Clinical Trial Center Wuerzburg, University Hospital Wuerzburg, Wuerzburg, Germany
,
Peter Heuschmann
7   Clinical Trial Center Wuerzburg, University Hospital Wuerzburg, Wuerzburg, Germany
8   Institute of Clinical Epidemiology and Biometry, University of Wuerzburg, Germany
,
Stefan Unterecker
9   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
,
Maike Scherf-Clavel
9   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
,
Hans Rock
10   Central Information Office, Department of Neurology, Philipps University of Marburg, Marburg, Germany
,
Gisela Antony
10   Central Information Office, Department of Neurology, Philipps University of Marburg, Marburg, Germany
,
Wolfgang Briegel
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
11   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Leopoldina Hospital, Schweinfurt, Germany
,
Christian Fleischhaker
12   Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany
,
Alexander Häge
13   Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
,
Tobias Hellenschmidt
14   Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatic Medicine, Vivantes Clinic Berlin Neukölln, Berlin, Germany
,
Harmut Imgart
15   Parkland-Clinic, Clinic for Psychosomatics and Psychotherapy, Academic Teaching hospital for the University Gießen, Bad Wildungen, Germany
,
Michael Kaess
16   Clinic for Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany
17   University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Switzerland
,
Andreas Karwautz
6   Department of Child and Adolescent Psychiatry, Medical University Vienna, Vienna, Austria
,
Michael Kölch
18   Department of Child and Adolescent Psychiatry and Psychotherapy, Brandenburg Medical School Brandenburg, Neuruppin, Germany
19   Department of Child and Adolescent Psychiatry, Neurology, Psychosomatics, and Psychotherapy, University Medical Center Rostock, Rostock, Germany
,
Karl Reitzle
20   Specialist practice and Medical Care Center for Child and Adolescent Psychiatry Munich, Munich, Germany
,
Tobias Renner
21   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
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
20   Specialist practice and Medical Care Center for Child and Adolescent Psychiatry Munich, Munich, Germany
,
Christian Rexroth
22   Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy at the Regensburg District Hospital, Medbo KU, University Hospital, Regensburg, Germany
,
Gerd Schulte-Körne
23   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-University (LMU) Hospital, Munich, Germany
,
Frank M. Theisen
24   Herz-Jesu-Krankenhaus gGmbH, Department of Child and Adolescent Psychiatry and Psychotherapy, Fulda, Germany
,
Susanne Walitza
25   Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, Switzerland
,
Christoph Wewetzer
26   Kliniken der Stadt Köln gGmbH, Clinic for Child and Adolescent Psychiatry Holweide, Children’s Hospital Amsterdamer Straße, Cologne, Germany
,
Stefanie Fekete
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
,
Regina Taurines
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
,
Marcel Romanos
1   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
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Abstract

Introduction Despite the growing evidence base for psychotropic drug treatment in pediatric patients, knowledge about the benefit-risk ratio in clinical practice remains limited. The ‘Therapeutic Drug Monitoring (TDM)-VIGIL’ study aimed to evaluate serious adverse drug reactions (ADRs) in children and adolescents treated with antidepressants and/or antipsychotics in approved (‘on-label’), and off-label use in clinical practice.

Methods Psychiatric pediatric patients aged 6-18 years treated with antidepressants and/or antipsychotics either on-label or off-label were prospectively followed between October 2014 and December 2018 within a multicenter trial. Follow-up included standardized assessments of response, serious ADRs and therapeutic drug monitoring.

Results 710 youth (age=14.6±2.2 years, female=66.6%) were observed for 5.5 months on average; 76.3% received antidepressants, 47.5% antipsychotics, and 25.2% both. Altogether, 55.2% of the treatment episodes with antidepressants and 80.7% with antipsychotics were off-label. Serious ADRs occurred in 8.3% (95%CI=6.4–10.6%) of patients, mainly being psychiatric adverse reactions (77.4%), predominantly suicidal ideation and behavior. The risk of serious ADRs was not significantly different between patients using psychotropics off-label and on-label (antidepressants: 8.1% vs. 11.3%, p=0.16; antipsychotics: 8.7% vs 7.5%, p=0.67). Serious ADRs occurred in 16.6% of patients who were suicidal at enrollment versus 5.6% of patients who were not suicidal (relative risk 3.0, 95%CI=1.9-4.9).

Conclusion Off-label use of antidepressants and antipsychotics in youth was not a risk factor for the occurrence of serious ADRs in a closely monitored clinical setting. Results from large naturalistic trials like ours can contribute to bridging the gap between knowledge from randomized controlled trials and real-world clinical settings.

Key words

antidepressants - antipsychotics - child - adverse drug reactions - safety


Publication History

Received: 09 September 2021
Received: 02 November 2021

Accepted: 29 November 2021

Article published online:
07 February 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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