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

Author:

Egberts Karin M.1,Gerlach Manfred1,Correll Christoph U.234,Plener Paul L.56,Malzahn Uwe7,Heuschmann Peter78,Unterecker Stefan9,Scherf-Clavel Maike9,Rock Hans10,Antony Gisela10,Briegel Wolfgang111,Fleischhaker Christian12,Häge Alexander13,Hellenschmidt Tobias14,Imgart Harmut15,Kaess Michael1617,Karwautz Andreas6,Kölch Michael1819,Reitzle Karl20,Renner Tobias21,Reuter-Dang Su-Yin120,Rexroth Christian22,Schulte-Körne Gerd23,Theisen Frank M.24,Walitza Susanne25,Wewetzer Christoph26,Fekete Stefanie1,Taurines Regina1,Romanos Marcel1

Affiliation:

1. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany

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

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

7. Clinical Trial Center Wuerzburg, University Hospital Wuerzburg, Wuerzburg, Germany

8. Institute of Clinical Epidemiology and Biometry, University of Wuerzburg, Germany

9. Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany

10. Central Information Office, Department of Neurology, Philipps University of Marburg, Marburg, Germany

11. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Leopoldina Hospital, Schweinfurt, Germany

12. Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany

13. Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany

14. Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatic Medicine, Vivantes Clinic Berlin Neukölln, Berlin, Germany

15. Parkland-Clinic, Clinic for Psychosomatics and Psychotherapy, Academic Teaching hospital for the University Gießen, Bad Wildungen, Germany

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

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

20. Specialist practice and Medical Care Center for Child and Adolescent Psychiatry Munich, Munich, Germany

21. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Psychiatry and Psychotherapy Tuebingen, Center of Mental Health Tuebingen, Germany

22. Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy at the Regensburg District Hospital, Medbo KU, University Hospital, Regensburg, Germany

23. Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-University (LMU) Hospital, Munich, Germany

24. Herz-Jesu-Krankenhaus gGmbH, Department of Child and Adolescent Psychiatry and Psychotherapy, Fulda, Germany

25. Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, Switzerland

26. Kliniken der Stadt Köln gGmbH, Clinic for Child and Adolescent Psychiatry Holweide, Children’s Hospital Amsterdamer Straße, Cologne, Germany

Abstract

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.

Publisher

Georg Thieme Verlag KG

Subject

Pharmacology (medical),Psychiatry and Mental health,General Medicine

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