Hiroyuki Uchida1, Takefumi Suzuki2, Ariel Graff-Guerrero3, Benoit H Mulsant4, Bruce G Pollock4, Tamara Arenovich5, Tarek K Rajji3, David C Mamo6. 1. Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan. 2. 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. 3. 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. 4. Geriatric Mental Health Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. 5. Biostatistical Consulting Service, Clinical Research Department, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. 6. 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.
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. 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 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. CONCLUSION: 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.
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. 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 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. CONCLUSION: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: Shinichiro Nakajima; Hiroyuki Uchida; Robert R Bies; Fernando Caravaggio; Takefumi Suzuki; Eric Plitman; Wanna Mar; Philip Gerretsen; Bruce G Pollock; Benoit H Mulsant; David C Mamo; Ariel Graff-Guerrero Journal: Schizophr Bull Date: 2015-07-28 Impact factor: 9.306
Authors: Mohamed Ismail; Thomas Straubinger; Hiroyuki Uchida; Ariel Graff-Guerrero; Shinichiro Nakajima; Takefumi Suzuki; Fernando Caravaggio; Philip Gerretsen; David Mamo; Benoit H Mulsant; Bruce G Pollock; Robert Bies Journal: Br J Clin Pharmacol Date: 2022-03-01 Impact factor: 3.716