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Discovering Interactions in Augmentation Strategies: Impact of Duloxetine on the Metabolism of Aripiprazole
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  • Teresa Margraff,
  • Georgios Schoretsanitis,
  • Irene Neuner,
  • Ekkehard Haen,
  • Arnim Gaebler,
  • Michael Paulzen
Teresa Margraff
RWTH Aachen University
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Georgios Schoretsanitis
1Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA
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Irene Neuner
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Ekkehard Haen
Universitätsklinikum Regensburg
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Arnim Gaebler
RWTH Aachen University
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Michael Paulzen
Alexianer Hospital Aachen

Corresponding Author:m.paulzen@alexianer.de

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Abstract

Objective: Combining different drugs increases the potential for drug-drug interactions en-hancing the risk of adverse drug reactions. We aimed to unravel potential pharma-cokinetic interactions between aripiprazole and duloxetine. Methods: Plasma concentrations of aripiprazole of two groups of 78 patients each, receiving aripiprazole as a monotherapy, or combined with duloxetine, were compared. A po-tential impact of duloxetine on the metabolism of aripiprazole was expected in high-er plasma concentrations of aripiprazole and higher dose-adjusted plasma concen-trations. Results: Patients co-medicated with duloxetine showed significantly higher plasma concen-trations of aripiprazole (p=0.019) by 54.2%. Dose-adjusted plasma concentrations were 45.6% higher (p=0.001). 65.4 % of these patients exhibited aripiprazole plasma concentrations above the upper limit of the therapeutic reference range, in the con-trol group this was only the case for 43.6% of the patients (p=0.006). A positive rela-tionship was found between the daily dose of duloxetine and dose-adjusted plasma concentrations of aripiprazole (p=0.034). Conclusions: Combining duloxetine and aripiprazole leads to significantly higher drug concentra-tions of aripiprazole, most likely via an inhibition of cytochrome P450 CYP2D6 and to a lesser extent of CYP3A4 by duloxetine. Clinicians have to consider increasing aripiprazole concentrations when adding duloxetine to a treatment regimen with ari-piprazole.
15 Jan 2023Submitted to Basic & Clinical Pharmacology & Toxicology
16 Jan 2023Review(s) Completed, Editorial Evaluation Pending
16 Jan 2023Submission Checks Completed
16 Jan 2023Assigned to Editor
20 Jan 2023Reviewer(s) Assigned
27 Feb 2023Editorial Decision: Revise Major
01 Apr 20231st Revision Received
03 Apr 2023Submission Checks Completed
03 Apr 2023Assigned to Editor
03 Apr 2023Review(s) Completed, Editorial Evaluation Pending
13 Apr 2023Editorial Decision: Accept