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D₂ Receptor Occupancy During High- and Low-Dose Therapy with the Atypical Antipsychotic Amisulpride: A ¹²³I-Iodobenzamide SPECT Study

¹ Department of Nuclear Medicine, University of Munich, Munich, Germany
² Department of Psychiatry, University of Munich, Munich, Germany

Amisulpride appears to be an effective agent for treating positive or negative symptoms of schizophrenia, depending on dose. The aim of this study was to assess striatal dopamine D₂ receptor availability by means of ¹²³I-iodobenzamide (IBZM) SPECT in patients treated with high and low doses of this atypical antipsychotic drug. Methods: Twenty-nine patients (19 men and 10 women, age range, 19–68 y) with schizophrenia treated with high doses (15 patients; 400–1,200 mg/d; mean dose, 666.7 ± 219.3 mg/d) or low doses (14 patients; 50–300 mg/d; mean dose, 228.6 ± 93.5 mg/d) of amisulpride were examined. For assessment of plasma amisulpride concentration, blood samples were taken. Brain SPECT was performed 2 h after intravenous injection of 185 MBq of ¹²³I-IBZM. For semiquantitative evaluation, transverse slices corrected for attenuation (Chang’s first-order method) were used to calculate specific binding in the striatum, with the frontal cortex used as background. Results: In all patients treated with amisulpride, specific binding of ¹²³I-IBZM to D₂ receptors was significantly lower (P < 0.001) than in healthy controls (0.95). Both groups treated with amisulpride differed significantly in specific binding of ¹²³I-IBZM to dopamine D₂ receptors (0.20 vs. 0.31, P < 0.05). D₂ receptor blockade correlated well with the administered dose of amisulpride and with amisulpride plasma concentration. Conclusion: Our findings suggest that amisulpride treatment leads to a significant occupancy of postsynaptic dopamine D₂ receptors. The blockade of D₂ receptors tends to be significantly lower in patients receiving low-dose amisulpride therapy than in patients receiving high-dose therapy.

Key Words: ¹²³I-IBZM SPECT • schizophrenia • amisulpride

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