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Analysis of smoking behavior on the pharmacokinetics of antidepressants and antipsychotics

evidence for the role of alternative pathways apart from CYP1A2

Scherf-Clavel, Maikea; Samanski, Lydiaa; Hommers, Leif G.a,b,c; Deckert, Jürgena; Menke, Andreasa,b,c; Unterecker, Stefana

International Clinical Psychopharmacology: March 2019 - Volume 34 - Issue 2 - p 93–100
doi: 10.1097/YIC.0000000000000250

Smoking is common among psychiatric patients and has been shown to accelerate the metabolism of different drugs. We aimed to determine the effect of smoking on the serum concentrations of psychopharmacological drugs in a naturalistic clinical setting. Dose-corrected, steady-state serum concentrations of individual patients were analyzed retrospectively by linear regression including age, sex, and smoking for amitriptyline (n=503), doxepin (n=198), mirtazapine (n=572), venlafaxine (n=534), clozapine (n=106), quetiapine (n=182), and risperidone (n=136). Serum levels of amitriptyline (P=0.038), clozapine (P=0.02), and mirtazapine (P=0.002) were significantly lower in smokers compared with nonsmokers after correction for age and sex. In addition, the ratios of nortriptyline/amitriptyline (P=0.001) and nordoxepin/doxepin (P=0.014) were significantly higher in smokers compared with nonsmokers. Smoking may not only induce CYP1A2, but may possibly also affect CYP2C19. Furthermore, CYP3A4, UGT1A3, and UGT1A4 might be induced by tobacco smoke. Hence, a different dosing strategy is required among smoking and nonsmoking patients. Nevertheless, the clinical relevance of the results remained unclear.

aDepartment of Psychiatry, Psychosomatics and Psychotherapy

bComprehensive Heart Failure Center, University Hospital of Würzburg

cInterdisciplinary Center for Clinical Research, University of Würzburg, Würzburg, Germany

Poster presented at the 13th symposium for therapeutic drug monitoring in psychiatry, Alpbach, Austria, 13–15 June 2018.

Correspondence to Maike Scherf-Clavel, PhD, Department of Psychiatry, Psychosomatics and Psychotherapy University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080 Würzburg, Germany Tel: +49 931 201 77546; fax: +49 931 201 77262; e-mail:

Received October 17, 2018

Accepted December 3, 2018

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.