D2 dopamine receptor occupancy, risperidone plasma level and extrapyramidal motor symptoms in previously drug-free schizophrenic patients

Rationale: A relationship between high D-2 occupancy (above 80%) and extrapyramidal-motor symptoms under neuroleptic treatment has been observed in several neuro imaging studies. Objectives: We investigated the striatal dopamine D-2 receptor occupancy, risperidone plasma level and extrapyramidal-motor symptoms in drug-free schizophrenic patients. Methods: Ten schizophrenic patients were treated with 3-6 mg risperidone daily. After four weeks administration, a [I-123]iodobenzamide ([I-123]IBZM)-single photon emission tomography (SPET) scan for determination of D-2 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. Results: The D-2 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. Conclusions: 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 D-2 receptor occupancy under risperidone treatment. This may help to minimize or even prevent extrapyramidal-motor symptoms'.