D2 dopamine receptor occupancy, risperidone plasma level and extrapyramidal motor symptoms in previously drug-free schizophrenic patients.
BACKGROUND
A relationship between high D2 occupancy (above 80%) and extrapyramidal-motor symptoms under neuroleptic treatment has been observed in several neuroimaging studies.


OBJECTIVE
We investigated the striatal dopamine D2 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 [(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.


RESULTS
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.


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 D2 receptor occupancy under risperidone treatment. This may help to minimize or even prevent extrapyramidal-motor symptoms.
Regenthal
R
R
Department of Clinical Pharmacology, University of Leipzig, Haertelstrasse 16-18, 04107 Leipzig, Germany. regenr@medizin.uni-leipzig.de
Kunstler
U
U
Hesse
S
S
Sabri
O
O
Preiss
R
R
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006236:Handwriting; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008875:Middle Aged; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018967:Risperidone / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D007457:Iodine Radioisotopes; D017448:Receptors, Dopamine D2; D018967:Risperidone