Pharmacopsychiatry 2022; 55(03): 169-170
DOI: 10.1055/s-0042-1747661
Abstracts | XIVth Symposium of the Task Force Therapeutic Drug Monitoring of the AGNP

Therapeutic drug monitoring of mirtazapine in children and adolescents: Analysis of dose, steady-state concentration and responsiveness in a naturalistic clinical setting

L. Smigielski
1   Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zürich, Switzerland
,
E. Tini
1   Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zürich, Switzerland
,
M. Romanos
2   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany
,
C. Wewetzer
3   Kliniken der Stadt Köln GmbH, Clinic for Child and Adolescent Psychiatry Holweide, Children's Hospital Amsterdamer Straße, Cologne, Germany
,
A. Karwautz
4   Department of Child and Adolescent Psychiatry, Medical University Vienna, Vienna, Austria
,
K. Reitzle
5   Specialist practice and Medical Care Center for Child and Adolescent Psychiatry Munich, Munich, Germany
,
C.U. Correll
6   Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany
7   The Zucker Hillside Hospital, Department of Psychiatry, Northwell Health, Glen Oaks, NY, USA
8   Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Department of Psychiatry and Molecular Medicine, Hempstead, NY, USA
,
P.L. Plener
9   Department of Child and Adolescent Psychiatry/Psychotherapy, University Hospital Ulm, Ulm, Germany
10   Department of Child and Adolescent Psychiatry, Medical University Vienna, Vienna, Austria
,
U. Malzahn
11   Clinical Trial Center Wuerzburg, University Hospital Wuerzburg, Wuerzburg, Germany
,
P. Heuschmann
11   Clinical Trial Center Wuerzburg, University Hospital Wuerzburg, Wuerzburg, Germany
12   Institute of Clinical Epidemiology and Biometry, University of Wuerzburg, Germany
,
S. Unterecker
13   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
,
M. Scherf-Clavel
13   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Wuerzburg, Germany
,
H. Rock
14   Central Information Office, Department of Neurology, Philipps University of Marburg, Marburg, Germany
,
G. Antony
14   Central Information Office, Department of Neurology, Philipps University of Marburg, Marburg, Germany
,
W. Briegel
2   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany
15   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Leopoldina Hospital, Schweinfurt, Germany
,
C. Fleischhaker
16   Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Freiburg, Freiburg, Germany
,
T. Banaschewski
17   Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
,
T. Hellenschmidt
18   Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatic medicine, Vivantes Clinic Berlin Neukölln, Berlin, Germany
,
H. Imgart
19   Parkland-Clinic, Clinic for Psychosomatics and Psychotherapy, academic teaching hospital for the University Gießen, Bad Wildungen, Germany
,
M. Kaess
20   Clinic for Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany
21   University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland
,
M. Kölch
22   Department of Child and Adolescent Psychiatry and Psychotherapy, Brandenburg Medical School Brandenburg, Neuruppin, Germany
23   Department of Child and Adolescent Psychiatry, Neurology, Psychosomatics, and Psychotherapy, University Medical Center Rostock, Rostock, Germany
,
T. Renner
24   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Psychiatry and Psychotherapy Tuebingen, Center of Mental Health Tuebingen, Germany
,
S.Y. Reuter-Dang
2   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany
25   Specialist practice and Medical Care Center for Child and Adolescent Psychiatry Munich, Munich, Germany
,
C. Rexroth
26   Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Regensburg at the Regensburg District Hospital, medbo KU, Regensburg, Germany
,
G. Schulte-Körne
27   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-University (LMU) Hospital, Munich, Germany
,
F. Theisen
28   Department of Child and Adolescent Psychiatry and Psychotherapy, Herz-Jesu-Krankenhaus gGmbH, Fulda, Germany
,
S. Fekete
2   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany
,
R. Taurines
2   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany
,
M. Gerlach
2   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany
,
K.M. Egberts
2   Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center for Mental Health, University Hospital of Wuerzburg, Wuerzburg, Germany
,
S. Walitza
1   Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric University Hospital Zurich, University of Zurich, Zürich, Switzerland
29   Zurich Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
30   Neuroscience Center Zurich, University of Zurich and ETH, Zurich, Switzerland
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*Equal contribution

Introduction Mirtazapine is a tetracyclic piperazino-azepine antidepressant with a unique mechanism of action through modulating serotonergic and noradrenergic neurotransmission. Being the second-choice medication in childhood depression, it is also used alone or as an add-on to treat insomnia, eating or other internalizing disorders. Despite its therapeutic benefits, no systematic therapeutic drug monitoring (TDM) examination of mirtazapine in children and adolescent exists.

Methods Within the prospective multicenter “TDM-VIGIL” study, valid datasets from 55 participants (48 females; mean age 15.75±1.16; range 13–17 years) treated with mirtazapine for various psychiatric indications were analyzed. Patient blood samples were collected at a steady-state and drug serum concentrations were determined using the isocratic reversed-phase high-performance liquid chromatography. Medication-specific treatment effects were quantified using an adapted version of the Clinical Global Impression (CGI) scale.

Results A strong dose–concentration effect was found (β=0.83, p<0.001, R2=0.683). The model with covariates, including sex, age, body weight, psychiatric co-medication and nicotine consumption, showed significant effects of age and co-medication. No effects with dose or serum concentration were observed with therapeutic and side effects, neither transdiagnostically nor separately for the two main diagnostic groups (depression, eating disorder). The 25th–75th interquartile range in good responders was 15–37 ng/ml.

Conclusions The effects of age and co-medication in this flexible-dose-TDM study are of relevance for pharmacovigilance and dose calibration in young patients treated with mirtazapine. The lack of associations with clinical improvement may potentially be explained by the heterogenous diagnostic and treatment picture, real-time scenario with uncontrollable variables and low signal-to-noise ratio.

Conflict of Interest KE, RT, MR, MG and PP received grant research support from BfArM. MR currently receives a research grant from Kids-Safe, Innovation Committee of the German Federal Joint Committee (G-BA grant number 01NVF16021). PP receives grant research support from the German Federal Ministry of Education and Research (BMBF) and was involved in clinical trials from Servier and Lundbeck; he received an advisor honorarium from Boehringer Ingelheim and speaker’s honoraria from Shire, Infectopharm and Gerot Lannach. CC has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Axsome, Damitsa, Gedeon Richter, Hikma, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, SK Life Science, Sumitomo Dainippon, Sunovion, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of LB Pharma. TB received personal fees from Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Takeda, Infectopharm, and Eli Lilly; serving as an advisor or consultant to Bristol Myers Squibb, Desitin Arzneimittel, Eli Lilly, Medice, Novartis, Pfizer, Shire, UCB, and Vifor Pharma; receiving conference attendance support, conference support, or speaking fees from Eli Lilly, Janssen McNeil, Medice, Novartis, Shire, and UCB; being involved in clinical trials conducted by Eli Lilly, Novartis, and Shire; and receiving royalties from Hogrefe, Kohlhammer, CIP-Medien, and Oxford University Press. SW has received in the last 5 years royalties from Thieme, Hogrefe, Kohlhammer, E. Tini et al. Comprehensive Psychiatry 115 (2022) 152301 9 Springer, Beltz. Her work was supported in the last 5 years by the Swiss National Science Foundation, diff. EU FP7s programs, Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, BfArM, ZInEP, Hartmann Müller Stiftung, Olga Mayenfisch, Gertrud Thalmann, Vontobel, Unicentia, Erika Schwarz Fonds, Gesundheitsforderung Schweiz. The other authors (ET, LS, CW, AK, KR, UM, SU, MS, HR, GA, WB, CF, TH, HI, MKae, MKo, TR, SR, CR, GS, FT, and SF) declare no conflict of interest.



Publication History

Article published online:
16 May 2022

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