Striatal dopamine-2 receptor occupancy as measured with [123I]iodobenzamide and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol
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Rationale. Extrapyramidal symptoms (EPS) are common with conventional antipsychotics. Clozapine and other novel antipsychotic substances with lower in vitro affinity for dopamine-2 (D2) receptors have a lower propensity to induce EPS.
Objective. We investigated whether striatal D2 receptor occupancy predicted the occurrence of EPS with atypical antipsychotics and the typical neuroleptic haloperidol.
Methods. [123I]Iodobenzamide (IBZM) and single photon emission tomography (SPECT) were used to quantify receptor occupancy in 71 patients treated with antipsychotics. EPS were rated according to the Simpson-Angus scale (SAS). EPS were deemed clinically relevant, if the SAS score was ≥5 and/or anticholinergic medication was required. Patients received atypical antipsychotic monotherapy for at least 14 days with amisulpride (n=2), clozapine (n=6), haloperidol (n=10), olanzapine (n=6), quetiapine (n=4), risperidone (n=14), sertindole (n=13), or zotepine (n=16).
Results. The striatal D2 receptor occupancy ranged from <20% to almost saturation. The lowest occupancy was seen with quetiapine and clozapine, the highest with haloperidol. Twenty-two of 71 patients (29%) experienced clinically relevant EPS. These patients displayed significantly higher mean striatal D2 receptor occupancy (77%) than those without EPS (61%; P=0.002). We found a positive correlation between the percentage of striatal D2 receptor occupancy and the SAS score (r=0.28; P=0.02), despite 18 of these patients receiving anticholinergics, thus lowering their SAS score.
Conclusions. Striatal D2 receptor occupancy as measured with [123I]IBZM and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol. In vivo imaging of brain receptors with SPECT may provide a useful clinical tool to titrate doses individually and avoid motor side effects in patients treated with novel antipsychotics.
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- Striatal dopamine-2 receptor occupancy as measured with [123I]iodobenzamide and SPECT predicted the occurrence of EPS in patients treated with atypical antipsychotics and haloperidol
Volume 162, Issue 1 , pp 42-49
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- SPECT [123I]Iodobenzamide Antipsychotics Extrapyramidal symptoms Schizophrenia
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- A1. Department of General Psychiatry, University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria,
- A2. Department of Clinical Neurology, University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria,
- A3. Department of Neuropsychiatry for Children and Adolescents, University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria,