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Am J Geriatr Psychiatry. 2012 Oct 31. [Epub ahead of print]

Therapeutic Window for Striatal Dopamine D2/3 Receptor Occupancy in Older Patients With Schizophrenia: A Pilot PET Study.

Author information

1
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.

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.

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