title: Cerebral D2 and 5-HT2 receptor occupancy in Schizophrenic patients treated with olanzapine or clozapine.
abstract: 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 pyramidal tolerability, were similar. In this sample of neuroleptic-refractory schizophrenic patients, olanzapine and clozapine showed a different pattern of occupancy of D2-like receptor despite a common lack of extrapyramidal side-effects.
authors.affiliation: IBFM-CNR, Department of Nuclear Medicine, University of Milan-Bicocca, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Moresco
authors.forename: Roberto
authors.initials: R
authors.lastname: Cavallaro
authors.forename: Cristina
authors.initials: C
authors.lastname: Messa
authors.forename: Daniele
authors.initials: D
authors.lastname: Bravi
authors.forename: Clara
authors.initials: C
authors.lastname: Gobbo
authors.forename: Laura
authors.initials: L
authors.lastname: Galli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lucignani
authors.forename: Cristina
authors.initials: C
authors.lastname: Colombo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rizzo
authors.forename: Isabella
authors.initials: I
authors.lastname: Velonà
authors.forename: Enrico
authors.initials: E
authors.lastname: Smeraldi
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Fazio
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D001569:Benzodiazepines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003024:Clozapine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D044348:Receptors, Serotonin, 5-HT2 / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D013134:Spiperone / Q000031:analogs & derivatives*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D003024:Clozapine; D005462:Fluorine Radioisotopes; D000077152:Olanzapine; D017448:Receptors, Dopamine D2; D044348:Receptors, Serotonin, 5-HT2; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D013134:Spiperone; C051175:3-N-(2-fluoroethyl)spiperone