Pharmacokinetic and Pharmacodynamic Interactions Between Carbamazepine and Aripiprazole in Patients With Schizophrenia

Abstract

Pharmacokinetic and pharmacodynamic interactions between carbamazepine and aripiprazole were studied in 18 inpatients with schizophrenia being treated with aripiprazole. The daily dose of aripiprazole was 24 mg in 15 cases and 12 mg in 3 cases. Carbamazepine 400 mg/d was coadministered for 1 week, and blood samples were taken twice before the start of carbamazepine coadministration and then 1 week after completion. In addition, on these days, the severity of illness and side effects were evaluated using the Positive and Negative Syndrome Scale and the Udvalg for Kliniske Undersøgelser side effects rating scale, respectively. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass spectrometric detection. Carbamazepine significantly decreased both plasma concentrations of aripiprazole and dehydroaripiprazole by 64% and 68%, respectively (P < 0.001). Despite these decreases in plasma concentrations, the total and negative scores in Positive and Negative Syndrome Scale, together with the neurological score in Udvalg for Kliniske Undersøgelser, decreased slightly but significantly (P < 0.05) after carbamazepine coadministration. The present study implies that carbamazepine augmentation may be effective for patients with schizophrenia treated with aripiprazole, although carbamazepine dramatically decreases plasma concentrations of aripiprazole and dehydroaripiprazole, by inducing the metabolism of these compounds.