Discovering Interactions in Augmentation Strategies: Impact of
Duloxetine on the Metabolism of Aripiprazole
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.