Plasma levels and estimated dopamine D₂ receptor occupancy of long-acting injectable risperidone during maintenance treatment of schizophrenia: a 3-year follow-up study

Introduction: Dopamine D₂ receptor occupancy levels needed for the maintenance treatment of schizophrenia remain to be elucidated. We examined 3-year clinical outcomes of patients with schizophrenia who received long-acting injectable risperidone (LAI risperidone) at baseline and investigated their dopamine D₂ receptor occupancy levels, estimated from plasma drug concentrations. Methods: A chart review of 52 outpatients with schizophrenia who participated in the original cross-sectional study was conducted to examine their 3-year clinical outcomes between April and September 2015. Patients who continued outpatient treatment with LAI risperidone without any usage of concomitant chlorpromazine equivalent antipsychotic dosage at >200 mg/day for the 3-year period were asked to participate in the follow-up assessments that included the Brief Psychiatric Rating Scale (BPRS) and estimated dopamine D₂ receptor occupancy levels at trough, using plasma concentrations of risperidone plus 9-hydroxyrisperidone. Data were compared with the same patients collected 3 years earlier. Results: Among the original 52 participants, 14 participants (27 %) continued outpatient treatment with LAI risperidone. Ten participants (19 %) provided plasma samples; mean ± SD measured trough concentration of risperidone plus 9-hydroxyrisperidone significantly increased from 22.9 ± 15.6 to 31.8 ± 17.5 ng/mL (P = 0.02). Estimated dopamine D₂ receptor occupancy numerically increased from 63.0 ± 10.9 to 69.0 ± 11.0 % (P = 0.12). A significant worsening was observed in the BPRS total score among these patients (mean ± SD, 34.3 ± 12.7 to 46.5 ± 16.9, P = 0.003). Conclusion: Paradoxically, the increased plasma concentration was found to be associated with a significant worsening of the clinical outcome. More investigations are indicated to shed further light on optimal levels of D₂ blockade in the maintenance treatment of schizophrenia.