Effects of Paroxetine on Plasma Concentrations of Aripiprazole and Its Active Metabolite, Dehydroaripiprazole, in Japanese Patients With Schizophrenia

Abstract

The effects of paroxetine coadministration on plasma concentrations of aripiprazole and its active metabolite, dehydroaripiprazole, were studied in 14 Japanese patients with schizophrenia. The patients had been treated with aripiprazole (24 mg/d in 5 cases, 12 mg/d in 5 cases, and 6 mg/d in 4 cases) for at least 2 weeks. Paroxetine 10 mg/d was coadministered during the first week, and the dose was increased to 20 mg/d during the second week. Blood samples were taken 3 times, before the start of paroxetine and then 1 and 2 weeks after paroxetine coadministration. On the same days, the severity of illness and extrapyramidal adverse effects were evaluated by the clinical global impressions and the Drug-Induced Extra-Pyramidal Symptoms Scale, respectively. Plasma concentrations of aripiprazole and dehydroaripiprazole were measured using liquid chromatography with mass spectrometric detection. Plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole during coadministration of paroxetine 10 and 20 mg/d were significantly (P < 0.05) higher (1.5-fold and 1.7-fold; 1.4-fold and 1.5-fold) than those before paroxetine coadministration. Those values during coadministration of paroxetine 20 mg/d were also significantly (P < 0.05) higher (1.1-fold and 1.1-fold) than those during coadministration of paroxetine 10 mg/d. Plasma concentrations of dehydroaripiprazole were unchanged throughout the study period. The mean clinical global impression score was significantly (P < 0.05) higher during the paroxetine 10 mg/d than that before coadministration, whereas the Drug-Induced Extra-Pyramidal Symptoms Scale scores remained unchanged during the study. This study suggests that lower doses (10-20 mg/d) of paroxetine coadministration increase plasma concentrations of aripiprazole and the sum of aripiprazole and dehydroaripiprazole.