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CC BY-NC-ND 4.0 · Pharmacopsychiatry 2022; 55(05): 246-254
DOI: 10.1055/a-1872-0613
Original Paper

Effects of Pharmacokinetic Gene Variation on Therapeutic Drug Levels and Antidepressant Treatment Response

Maike Scherf-Clavel   *
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
,
Heike Weber   *
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
,
Catherina Wurst
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
2   Interdisciplinary Center for Clinical Research, University Hospital of Würzburg, Würzburg, Germany
3   Comprehensive Heart Failure Center (CHFC), University Hospital of Würzburg, Würzburg, Germany
,
Saskia Stonawski
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
2   Interdisciplinary Center for Clinical Research, University Hospital of Würzburg, Würzburg, Germany
3   Comprehensive Heart Failure Center (CHFC), University Hospital of Würzburg, Würzburg, Germany
,
Leif Hommers
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
2   Interdisciplinary Center for Clinical Research, University Hospital of Würzburg, Würzburg, Germany
3   Comprehensive Heart Failure Center (CHFC), University Hospital of Würzburg, Würzburg, Germany
,
Stefan Unterecker
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
,
Christiane Wolf
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
,
Katharina Domschke
4   Department of Psychiatry and Psychotherapy, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
,
Nicolas Rost
5   Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
6   International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany
,
Tanja Brückl
5   Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
,
Susanne Lucae
7   Max Planck Institute of Psychiatry, Munich, Germany
,
Manfred Uhr
7   Max Planck Institute of Psychiatry, Munich, Germany
,
Elisabeth B. Binder   †
5   Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
,
Andreas Menke   †
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
8   Department of Psychosomatic Medicine and Psychotherapy, Medical Park Chiemseeblick, Bernau, Germany
9   Department of Psychiatry and Psychotherapy, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany
,
Jürgen Deckert   †
1   Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Würzburg, Germany
› Author Affiliations Funding N. Rost is supported by the International Max Planck Research School of Translational Psychiatry (IMPRS-TP) and received funding from the Bavarian Ministry of Economic Affairs, Regional Development and Energy (BayMED, PBN_MED-1711-0003).
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Abstract

Introduction Pharmacogenetic testing is proposed to minimize adverse effects when considered in combination with pharmacological knowledge of the drug. As yet, limited studies in clinical settings have investigated the predictive value of pharmacokinetic (pk) gene variation on therapeutic drug levels as a probable mechanism of adverse effects, nor considered the combined effect of pk gene variation and drug level on antidepressant treatment response.

Methods Two depression cohorts were investigated for the relationship between pk gene variation and antidepressant serum concentrations of amitriptyline, venlafaxine, mirtazapine and quetiapine, as well as treatment response. For the analysis, 519 patients (49% females; 46.6±14.1 years) were included.

Results Serum concentration of amitriptyline was associated with CYP2D6 (higher concentrations in poor metabolizers compared to normal metabolizers), of venlafaxine with CYP2C19 (higher concentrations in intermediate metabolizers compared to rapid/ultrarapid metabolizers) and CYP2D6 (lower metabolite-to-parent ratio in poor compared to intermediate and normal metabolizers, and intermediate compared to normal and ultrarapid metabolizers). Pk gene variation did not affect treatment response.

Discussion The present data support previous recommendations to reduce starting doses of amitriptyline and to guide dose-adjustments via therapeutic drug monitoring in CYP2D6 poor metabolizers. In addition, we propose including CYP2C19 in routine testing in venlafaxine-treated patients to improve therapy by raising awareness of the risk of low serum concentrations in CYP2C19 rapid/ultrarapid metabolizers. In summary, pk gene variation can predict serum concentrations, and thus the combination of pharmacogenetic testing and therapeutic drug monitoring is a useful tool in a personalized therapy approach for depression.

Key words

pharmacogenetics - depressive disorder - serum concentrations - pharmacokinetics

* shared first authorship


† shared last authorship


Supplementary Material



Publication History

Received: 02 December 2021
Received: 27 May 2022

Accepted: 01 June 2022

Article published online:
15 July 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/).

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