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

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.

Original languageEnglish
JournalAmerican Journal of Geriatric Psychiatry
DOIs
Publication statusAccepted/In press - 2012 Oct 31
Externally publishedYes

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

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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, 31.10.2012.

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. 2012.
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