title: Therapeutic Window for Striatal Dopamine D2/3 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 D2/3 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 D2/3 relative receptor occupancy (RRO) on clinical outcomes in this population. DESIGN:: Open-label intervention. SETTING:: Centre for Addiction and Mental Health, Toronto. PARTICIPANTS:: Subjects with schizophrenia age 50 years or more who were clinically stable and previously maintained on oral risperidone for more than 6 months. INTERVENTION:: A dose reduction of risperidone of up to 40%, followed by a 3-month follow-up. MEASUREMENTS:: Dopamine D2/3 RRO in dorsal putamen was assessed, using the region of interest analysis of [C]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 D2/3 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% D2/3 RRO. CONCLUSION:: EPS diminished less than 70% D2/3 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: From the Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada (HU, TS, AG-G, BHM, BGP, TKR, DCM); Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan (HU, TS); Department of Psychiatry, University of Toronto (TS, AG-G, BHM, BGP, TKR, DCM), Multimodal Imaging Group, PET Centre, Centre for Addiction and Mental Health (TS, AG-G, TKR, DCM), and Biostatistical Consulting Service, Clinical Research Department, Centre for Addiction and Mental Health (TA), Toronto, Ontario, Canada.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uchida
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
authors.forename: Benoit H
authors.initials: BH
authors.lastname: Mulsant
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Pollock
authors.forename: Tamara
authors.initials: T
authors.lastname: Arenovich
authors.forename: Tarek K
authors.initials: TK
authors.lastname: Rajji
authors.forename: David C
authors.initials: DC
authors.lastname: Mamo