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Cerebral D2 and 5-HT2 Receptor occupancy in Schizophrenic Patients Treated with Olanzapine Or Clozapine

IBFM-CNR, Department of Nuclear Medicine, University of Milan-Bicocca, San Raffaele Scientific Institute, Milan, Italy

Roberto Cavallaro

Department of Psychiatry, Vita-Salute S. Raffaele University, San Raffaele Scientific Institute Hospital, Milan, Italy

Cristina Messa

IBFM-CNR, Department of Nuclear Medicine, University of Milan-Bicocca, San Raffaele Scientific Institute, Milan, Italy

Daniele Bravi

Medical Division Eli Lilly S.p.A Sesto Fiorentino, Italy

Clara Gobbo

IBFM-CNR, Department of Nuclear Medicine, University of Milan-Bicocca, San Raffaele Scientific Institute, Milan, Italy

Laura Galli

San Raffaele Scientific Institute, Milan, Italy

Giovanni Lucignani

Institute of Radiological Sciences, University of Milan, Ospedale Luigi Sacco, Milan, Italy

Cristina Colombo

Department of Psychiatry, Vita-Salute S. Raffaele University, San Raffaele Scientific Institute Hospital, Milan, Italy

Giovanna Rizzo

IBFM-CNR, Department of Nuclear Medicine, University of Milan-Bicocca, San Raffaele Scientific Institute, Milan, Italy

Isabella Velonà

Medical Division Eli Lilly S.p.A Sesto Fiorentino, Italy

Enrico Smeraldi

Department of Psychiatry, Vita-Salute S. Raffaele University, San Raffaele Scientific Institute Hospital, Milan, Italy

Ferruccio Fazio

IBFM-CNR, Department of Nuclear Medicine, University of Milan-Bicocca, San Raffaele Scientific Institute, Milan, Italyfazio{at}mednuc.hsr.it

We report the results of a double-blind, randomized prospective trial on D₂ and 5-HT₂ receptor occupancy and the clinical effects of olanzapine versus clozapine in a sample of neuroleptic-refractory schizophrenic patients. Receptor occupancy was evaluated in different cortical areas and in basal ganglia using [¹⁸F] fluoro-ethyl-spiperone ([¹⁸F] FESP) and positron emission tomography (PET). A total of 15 neuroleptic-free patients completed the study undergoing a baseline and a post-treatment PET scan (olanzapine, nine patients, one female; clozapine, six patients, three female) 8 weeks after starting treatment. PET data were analysed both by regions of interest and on a voxel-by-voxel basis using Statistical Parametric Mapping (SPM96). Olanzapine and clozapine induced a similar and significant inhibition of [¹⁸F] FESP binding index in the cortex. In the basal ganglia, receptor occupancy was significantly higher with olanzapine than with clozapine (p = 0.0018). By contrast, no differences in receptor occupancy were detected at the level of the pituitary gland. Clinical outcomes, in particular a full extra pyramidaltolerability, were similar. In this sample of neuroleptic-refractoryschizophrenic patients, olanzapine and clozapine showed a differentpattern of occupancy of D₂-like receptor despite a common lack of extrapyramidal side-effects.

Key Words: basal ganglia • clozapine • emission tomography • olanzapine • pituitary • receptor occupancy

Journal of Psychopharmacology, Vol. 18, No. 3, 355-365 (2004)
DOI: 10.1177/026988110401800306


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