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

• DOI: 10.1007/s00213-016-4428-1
• Publication Date: 2016-09-08T07:43:17Z
• Authors: Saeko Ikai; Takefumi Suzuki; Masaru Mimura; Hiroyuki Uchida
• Keywords: Adult; Male; Receptors, Dopamine D2; Middle Aged; Risperidone; 16. Peace & justice; Maintenance Chemotherapy; 3. Good health; 03 medical and health sciences; Cross-Sectional Studies; 0302 clinical medicine; Delayed-Action Preparations; Paliperidone Palmitate; Schizophrenia; Brief Psychiatric Rating Scale; Humans; Female; Aged; Antipsychotic Agents; Follow-Up Studies

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.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.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).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.