Effects of the augmentation with quetiapine or olanzapine on the metabolism of duloxetine: a retrospective analysis

Abstract

Background: In antidepressant augmentation strategies, olanzapine or quetiapine are often concomitantly administered to duloxetine. The use of the same enzymes for the degradation of the drugs may lead to clinically relevant drug-drug-interactions, DDIs. So far, DDIs between olanzapine or quetiapine and duloxetine have only been studied in rats or in small numbers of patients.

Methods: Out of a large therapeutic drug monitoring (TDM) database of duloxetine concentrations, three matched study groups were considered to investigate potential DDIs: a group of patients co-medicated with olanzapine (n = 81), a group co-medicated with quetiapine (n = 105) and a control group receiving only duloxetine (n = 105).

Results: Neither in the olanzapine group, nor in the quetiapine group, duloxetine plasma concentrations or dose-adjusted plasma concentrations differed significantly from the control group (p = 0.6759; p = 0.5841). The proportion of patients within the so-called therapeutic reference range was similar in all three groups (p = 0.635). However, smokers showed by 30% lower duloxetine plasma concentrations (p = 0.0179) and 32.5% lower dose-adjusted concentrations (p = 0.0003) compared to nonsmokers.

Conclusion: Our findings indicate that the combination of duloxetine and olanzapine or quetiapine is - from a pharmacokinetic view - a safe treatment option. TDM should be applied in case of co-medications to enhance therapeutic effectiveness and patients' safety.

Keywords: KONBEST; Therapeutic drug monitoring; cytochrome; duloxetine; interaction; olanzapine; pharmacokinetics; quetiapine.