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Pharmacopsychiatry. 2019 Oct 15. doi: 10.1055/a-1021-8827. [Epub ahead of print]

The Effects of Co-prescription of Pantoprazole on the Clozapine Metabolism.

Author information

Psychiatric and Psychotherapeutic Private Clinic Clienia Schlössli, Academic Teaching Hospital of the University of Zurich, Oetwil am See, Switzerland.
The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, New York, USA.
Department of Psychiatry and Psychotherapy, Clinical Pharmacology, University of Regensburg, Regensburg, Germany.
Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany.
Psychiatric Services of Thurgovia, Academic Teaching Hospital of the Medical University of Salzburg, Münsterlingen, Switzerland.
Department of Psychiatry and Psychotherapy and Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of Mainz, Germany.
Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Alexianer Hospital Aachen, Aachen, Germany.
Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, and JARA - Translational Brain Medicine, Jülich, Germany.
Contributed equally



Polypharmacy including somatic medications such as proton pump inhibitors is a common phenomenon in psychiatric care. The aim of this study was to evaluate the pantoprazole effects on clozapine metabolism.


A large therapeutic drug-monitoring database containing plasma concentrations of CLZ was analyzed. The results were stratified into four groups: a non-smoking (n=250) and a smoking group (n=326), and two groups co-medicated with pantoprazole: non-smokers (n=26) and smokers (n=29). The analysis was based on the non-parametrical Mann-Whitney U test (M-W-U) with a significance level of 0.05.


Differences reached statistical significance for pharmacokinetic parameters between CLZ monotherapy and co-medication with pantoprazole neither in smokers nor in non-smokers (p>0.05 for M-W-U in pairwise comparisons). In patients with clozapine monotherapy, smokers had a higher daily dosage of CLZ compared to non-smokers (mean dosage 363±181 vs. 291±145 mg/day, p<0.001 for M-W-U).


Adding pantoprazole to an ongoing treatment with clozapine does not alter the metabolism of clozapine to a significant extent.


Conflict of interest statement

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Ekkehard Haen received speaker’s or consultancy fees from the following pharmaceutical companies: Servier, Novartis, and Janssen-Cilag. He is managing director of AGATE, a non-profit working group to improve drug safety and efficacy in the treatment of psychiatric diseases. He reports no conflict of interest with this publication. Gerhard Gründer has served as a consultant and advisory board member during the last three years for the following companies and institutions: Allergan, Boehringer Ingelheim, Eli Lilly, IQWiG, Janssen-Cilag, Lundbeck, Otsuka, Recordati, Roche, Servier, and Takeda. He has received honoraria as a speaker for Janssen-Cilag, Lundbeck, Neuraxpharma, Otsuka and Recordati. He has received funding for clinical trials from Boehringer Ingelheim, Lundbeck and Saladax. He is the founder and partner of Brainfoods GmbH, InMedicon GmbH, and Mind and Brain Institute GmbH. Christoph Hiemke has received speaker or consultancy fees from the following pharmaceutical companies: Astra Zeneca, Janssen-Cilag, Pfizer, Lilly and Servier. He is managing director of psiac GmbH, which provides an Internet-based drug–drug interaction program for psychopharmacotherapy. He reports no conflict of interest with this publication. Maxim Kuzin received travel grants from Sunovion Pharmaceutical (Basel, Switzerland) and Otsuka Pharmaceutical (Glattburgg, Switzerland). He also received a travel grant and remuneration to participate on the speaker’s board of Lundbeck (Zurich, Switzerland). All other authors report no conflicts of interest.

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