title: Plasma levels and estimated dopamine D2receptor occupancy of long-acting injectable risperidone during maintenance treatment of schizophrenia: a 3-year follow-up study.
abstract: Dopamine D2receptor 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 D2receptor 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 D2receptor 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 D2receptor 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 D2blockade in the maintenance treatment of schizophrenia.
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Ikai
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.|Department of Psychiatry, Inokashira Hospital, 4-14-1, Kamirenjaku, Mitaka, Tokyo, 181-0012, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Mimura
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. hiroyuki.uchida.hu@gmail.com.|Geriatric Mental Health Program, Centre for Addiction and Mental Health, 1001 Queen St W, Toronto, ON, M6J 1H4, Canada. hiroyuki.uchida.hu@gmail.com.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D010054:Brief Psychiatric Rating Scale; D003430:Cross-Sectional Studies; D003692:Delayed-Action Preparations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D060046:Maintenance Chemotherapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate / Q000097:blood*; D017448:Receptors, Dopamine D2 / Q000097:blood*; D018967:Risperidone / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D017448:Receptors, Dopamine D2; D018967:Risperidone; D000068882:Paliperidone Palmitate
keywords: Antipsychotics; Dopamine; Long-acting injection; Maintenance; Risperidone; Schizophrenia