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S056-4

Optimal Dopamine D2/3 Receptor Occupancy by Antipsychotics in Patients with
Late-Life Schizophrenia: A [11C]-Raclopride PET Study

Shinichiro Nakajima1, Ariel Graff-Guerrero2, Hiroyuki Uchida3, Takefumi Suzuki3, Fernando
Caravaggio2, Wanna Mar2, Philip Gerretsen2, Tarek Rajji2, Benoit Mulsant2, Bruce Pollock2, David
Mamo4

1Centre for Addiction and Mental Health, Japan 2Centre for Addiction and Mental Health, Canada 3Keio
University, Japan 4University of Malta, Malta

Background/Objective: Patients with late-life schizophrenia (LLS) are highly susceptible to
antipsychotics’ adverse effects. Treatment guidelines recommend lower antipsychotics dosages but
they are not based on empirical data. The optimal dose of antipsychotics and associated dopamine
D2/3 receptors (D2/3R) occupancies remain largely unexplored in this population. This study was
aimed to evaluate effects of antipsychotic dose reduction on striatal dopamine D2/3R occupancies
and clinical outcomes in patients with LLS.

Method: The study included outpatients with stable schizophrenia, ≧50 years, treated with the
same dose of antipsychotics for ≧6 months. [11C]-raclopride PET scans were performed before and
after dose reduction. Antipsychotic dose was gradually reduced to 60% of the baseline dose with a
target dose not lower than the recommended dose. Subjects were clinically followed-up for six
months using Positive and Negative Syndrome Scale, PANSS; Brief Psychiatric Rating Scale, BPRS;
Simpson Angus Scale, SAS; Barnes Rating Scale for Drug-Induced Akathisia, BAS; and Udvalg for
Kliniske Undersøgelser Side Effect Rating Scale, UKU. Relationships between clinical outcomes
and striatal D2/3R occupancies were assessed.

Result: 35 subjects (age=60.1±7.0 years, PANSS=61.3±14.4, risperidone/olanzapine=4.4±2.7
/20.8±6.6 mg/day) were included. D2/3R occupancies decreased from 70±12% to 64±12%. The
lowest D2/3R occupancy associated with clinical stability was 50%. Extrapyramidal symptoms were
more likely shown with D2/3R occupancies higher than 60%. The baseline D2/3R occupancies were
lower in patients with clinical deterioration (N=5) than in the 85% that remained stable (N=29)
(58±15% vs. 72±10%, p=.02). Following dose reduction, decreases were observed in PANSS (p=.02),
BPRS (p=.03); SAS (p<.001), BAS (p=.03), UKU (p<.001), and prolactin level (p<.001).

Conclusion: Antipsychotic dose reduction is feasible in stable patients with LLS, improving
antipsychotics’ side effects and illness severity measures. The results suggest that D2/3R occupancy
is associated with a lower therapeutic window in patients with LLS (50%–60%) than previously
reported in younger patients (65%–80%).