A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable: Implications for dopamine D₂ receptor occupancy during maintenance treatment in schizophrenia

Objective: While 65%-80% occupancy of dopamine D₂ receptors with antipsychotics has been proposed to achieve optimal therapeutic response during acute treatment of schizophrenia, it remains unclear as to whether it is also necessary to maintain D₂ receptor occupancy within this "safe" window for ongoing maintenance treatment. The data are especially scarce for long-acting antipsychotic formulations. Method: Clinically stable patients with schizophrenia (DSM-IV) receiving a stable dose of risperidone long-acting injectable (LAI) as antipsychotic monotherapy for at least 3 months and free of any psychiatric hospitalization over the past 6 months were included. Dopamine D₂ receptor occupancy levels at trough were estimated from plasma concentrations of risperidone plus 9-hydroxyrisperidone immediately before the intramuscular injection of risperidone LAI, using a 1-site binding model derived from our previous positron emission tomography data. This study was conducted from October to December 2011. Results: 36 patients were included in this study (mean ± SD age, 49.3 ± 14.0 years; mean ± SD dose and interval of injections, 38.2 ± 11.6 mg and 16.5 ± 14.0 days, respectively). Mean ± SD D₂ receptor occupancy was 62.1% ± 15.4%; 52.8% of the subjects (n = 19) did not demonstrate an occupancy of ≥ 65%. On the other hand, 13.9% (n = 5) showed a D₂ occupancy as high as over 80% at the estimated trough. Conclusions: More than half of patients taking risperidone LAI maintained clinical stability without achieving continuous blockade of dopamine D₂ receptors ≥ 65% in real-world clinical settings. Results suggest that sustained dopamine D₂ receptor occupancy levels of ? 65% may not be necessary for maintenance treatment with risperidone LAI in schizophrenia.