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

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. 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 (<i>n</i> = 81), a group co-medicated with quetiapine (<i>n</i> = 105) and a control group receiving only duloxetine (<i>n</i> = 105). Neither in the olanzapine group, nor in the quetiapine group, duloxetine plasma concentrations or dose-adjusted plasma concentrations differed significantly from the control group (<i>p</i> = 0.6759; <i>p</i> = 0.5841). The proportion of patients within the so-called therapeutic reference range was similar in all three groups (<i>p</i> = 0.635). However, smokers showed by 30% lower duloxetine plasma concentrations (<i>p</i> = 0.0179) and 32.5% lower dose-adjusted concentrations (<i>p</i> = 0.0003) compared to nonsmokers. 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.