loading page

Discovering Interactions in Augmentation Strategies: Impact of Duloxetine on the Metabolism of Aripiprazole
  • +3
  • Teresa Margraff,
  • Georgios Schoretsanitis,
  • Irene Neuner,
  • Ekkehard Haen,
  • Arnim Gaebler,
  • Michael Paulzen
Teresa Margraff
RWTH Aachen University
Author Profile
Georgios Schoretsanitis
1Department of Psychiatry, The Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA
Author Profile
Irene Neuner
Author Profile
Ekkehard Haen
Universitätsklinikum Regensburg
Author Profile
Arnim Gaebler
RWTH Aachen University
Author Profile
Michael Paulzen
Alexianer Hospital Aachen

Corresponding Author:[email protected]

Author Profile


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