title: A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable: implications for dopamine D2 receptor occupancy during maintenance treatment in schizophrenia.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Ikai
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuboi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Den
authors.forename: Jinichi
authors.initials: J
authors.lastname: Hirano
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tsunoda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nishimoto
authors.forename: Koichiro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Masaru
authors.initials: M
authors.lastname: Mimura
authors.forename: David
authors.initials: D
authors.lastname: Mamo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D003430:Cross-Sectional Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007273:Injections, Intramuscular; D007555:Isoxazoles / Q000493:pharmacokinetics; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D011743:Pyrimidines / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D007555:Isoxazoles; D011743:Pyrimidines; D017448:Receptors, Dopamine D2; D018967:Risperidone; D000068882:Paliperidone Palmitate