Changes in plasma concentrations of risperidone and 9-hydroxyrisperidone and the associated clinical effects during the switch from oral risperidone to extended-release paliperidone tablets in patients with schizophrenia.

This study aimed to investigate changes in plasma concentrations of risperidone and 9-hydroxy-risperidone (9-OHR) and the associated clinical effects when switching from oral risperidone to extended-release (ER) paliperidone in patients with schizophrenia. This study included 25 patients with schizophrenia. Following a one-week screening period with a stable dose of risperidone, a six-week open-label switch study from risperidone to extended-release paliperidone (paliperidone ER) was conducted. Efficacy and safety assessments were performed on Day 1 and at Weeks 1, 2, 4, and 6. Plasma levels of the active fractions of oral risperidone and paliperidone ER were measured on Day 1 and at Week 1, respectively. Plasma levels of the active moiety (risperidone plus 9-OHR) while taking risperidone (mean dose: 4.0 mg) were significantly higher than plasma levels of 9-OHR while taking 6 mg of paliperidone ER. For 12 subjects taking only 3 mg of risperidone, plasma concentrations of the active moiety of risperidone were also significantly higher than those of 9-OHR while taking 6 mg of paliperidone ER. The amount of reduction in plasma levels was correlated with a temporal deterioration of clinical symptoms. These findings suggest that for patients with schizophrenia taking 3 mg or more of risperidone, an initial switching dose of 6 mg of paliperidone ER may be relatively low in terms of subsequent plasma concentrations and the associated clinical response.