Abstract
A relationship between high D2 occupancy (above 80%) and extrapyramidal-motor symptoms under neuroleptic treatment has been observed in several neuroimaging studies. We investigated the striatal dopamine D2 receptor occupancy, risperidone plasma level and extrapyramidal-motor symptoms in drug-free schizophrenic patients. Ten schizophrenic patients were treated with 3 - 6 mg risperidone daily. After four weeks administration, a [(123)I]iodobenzamide ([(123)I]IBZM)-single photon emission tomography (SPET) scan for determination of D2 receptor occupancy was carried out (in eight responders) and compared to a control group. Plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (active moiety) were determined by high performance liquid chromatography and electrochemical detection. Extrapyramidal-motor symptoms were assessed by means of the Simpson-Angus-Scale and a handwriting test before treatment and coincident with the scan. The D2 receptor occupancy (Mean 62%, SD 13%) positively correlated with the plasma level of the risperidone active moiety as well as with the reduction in handwriting area. Multiple linear regression revealed an inherent relationship with a coefficient of determination of r = 0.956 (p = 0.02). No clinical relevant extrapyramidal-motor symptoms were observed. In drug-free schizophrenic responders, the simultaneous assessment of both plasma level and reduction in handwriting area may be a useful clinical tool for a surrogate estimate of D2 receptor occupancy under risperidone treatment. This may help to minimize or even prevent extrapyramidal-motor symptoms.
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