Therapeutic window for striatal dopamine D2/3 receptor occupancy in older patients with schizophrenia: A pilot PET study

Hiroyuki Uchida, Takefumi Suzuki, Ariel Graff-Guerrero, Benoit H. Mulsant, Bruce G. Pollock, Tamara Arenovich, Tarek K. Rajji, David C. Mamo

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 [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 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.

Original languageEnglish
Pages (from-to)1007-1016
Number of pages10
JournalAmerican Journal of Geriatric Psychiatry
Volume22
Issue number10
DOIs
Publication statusPublished - 2014 Oct 1

Fingerprint

Corpus Striatum
Dopamine D2 Receptors
Positron-Emission Tomography
Risperidone
Schizophrenia
Putamen
Raclopride
Therapeutics
Dopamine
Mental Health
Guidelines
Pharmaceutical Preparations
Population

Keywords

  • Aging
  • antipsychotic
  • dopamine
  • PET
  • risperidone
  • schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology

Cite this

Therapeutic window for striatal dopamine D2/3 receptor occupancy in older patients with schizophrenia : A pilot PET study. / Uchida, Hiroyuki; Suzuki, Takefumi; Graff-Guerrero, Ariel; Mulsant, Benoit H.; Pollock, Bruce G.; Arenovich, Tamara; Rajji, Tarek K.; Mamo, David C.

In: American Journal of Geriatric Psychiatry, Vol. 22, No. 10, 01.10.2014, p. 1007-1016.

Research output: Contribution to journalArticle

Uchida, Hiroyuki ; Suzuki, Takefumi ; Graff-Guerrero, Ariel ; Mulsant, Benoit H. ; Pollock, Bruce G. ; Arenovich, Tamara ; Rajji, Tarek K. ; Mamo, David C. / Therapeutic window for striatal dopamine D2/3 receptor occupancy in older patients with schizophrenia : A pilot PET study. In: American Journal of Geriatric Psychiatry. 2014 ; Vol. 22, No. 10. pp. 1007-1016.
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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 [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 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.",
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AU - Mulsant, Benoit H.

AU - Pollock, Bruce G.

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