title: Therapeutic window for striatal dopamine D(2/3) receptor occupancy in older patients with schizophrenia: a pilot PET study.
abstract: OBJECTIVE
  In younger patients with schizophrenia, positron emission tomography (PET) studies have identified a therapeutic window of striatal dopamine D(2/3) receptor occupancy of 65%-80%. This type of empirical information is not available in late life. Our primary aim was to assess the effect of changes in D(2/3) relative receptor occupancy (RRO) on clinical outcomes in this population.
  
  
  METHODS
  Open-label intervention.
  
  
  METHODS
  Centre for Addiction and Mental Health, Toronto.
  
  
  METHODS
  Subjects with schizophrenia age 50 years or more who were clinically stable and previously maintained on oral risperidone for D(2/3) RRO in dorsal putamen was assessed, using the region of interest analysis of [¹¹C]raclopride PET scans, before and after the dose reduction. Clinical assessments included the Positive and Negative Syndrome Scale and the Simpson-Angus Scale.
  
  
  RESULTS
  Nine subjects (mean ± SD age: 58 ± 7 years; mean ± SD baseline risperidone dose: 3.4 ± 1.6 mg/day) participated in the study. Extrapyramidal symptoms (EPS) were present in six subjects and were associated with 70% or more D(2/3) RRO in the putamen (range: 70%-87%). Following the dose reduction, EPS resolved in five subjects. Two subjects experienced a clinical worsening at 52% and at less than 50% D(2/3) RRO.
  
  
  CONCLUSIONS
  EPS diminished less than 70% D(2/3) RRO, which suggests a lower therapeutic window for older patients with schizophrenia than that for younger patients. Although these findings have to be replicated in a larger sample, they have important implications for future drug development and clinical guidelines in late-life schizophrenia.
authors.affiliation: Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
authors.affiliation: Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Multimodal Imaging Group, PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Multimodal Imaging Group, PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
authors.affiliation: Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.affiliation: Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.affiliation: Biostatistical Consulting Service, Clinical Research Department, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Tamara
authors.initials: T
authors.lastname: Arenovich
authors.affiliation: Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Multimodal Imaging Group, PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.affiliation: Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Multimodal Imaging Group, PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Electronic address: mamodc@gmail.com.
authors.forename: David C
authors.initials: DC
authors.lastname: Mamo
mesh_terms: D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D018967:Risperidone / Q000008:administration & dosage* / Q000009:adverse effects*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride; D018967:Risperidone
keywords: Aging; PET; antipsychotic; dopamine; risperidone; schizophrenia