A positron emission tomography study of quetiapine in schizophrenia - A preliminary finding of an antipsychotic effect with only transiently high dopamine D-2 receptor occupancy

Background: Quetiapine is a new atypical antipsychotic medication. As such, relatively little has been published regarding its in vivo effects at the dopamine type 2 (D-2) and serotonin type 2a (5-HT2a) receptor systems. The following study was undertaken to explore these effects across the clinical dose range and relate this information to its clinical profile. Methods: Twelve patients with schizophrenia were randomly assigned to doses of 150 to 600 mg/d (n=3, at 150, 300, 450, and 600 mg/d) of quetiapine. Af ter 3 weeks of treatment, D-2 and 5-HT2a occupancy were measured using posi tron emission tomography (PET) imaging, 12 to 14 hours after the last dose. Clinical efficacy and adverse effect ratings were obtained at baseline, at the time of PET scanning, and at 12 weeks. Two additional patients were in cluded to examine the effects of the drug 2 to 3 hours after last dose. Results: Quetiapine was an effective antipsychotic and improved the extrapy ramidal symptoms and prolactin level elevation noted at baseline. It achiev ed these results with minimal (0%-27%) D-2 occupancy 12 hours after the las t dose. Study of the additional subjects revealed that quetiapine does give rise to transiently high (58%-64%) D-2 occupancy 2 to 3 hours after a sing le dose that then decreases to minimal levels in 12 hours. Conclusions: Quetiapine shows a transiently high D-2 occupancy, which decre ases to very low levels by the end of the dosing interval. Quetiapine's low D-2 occupancy can explain its freedom from extrapyramidal symptoms and pro lactin level elevation. The data suggest that transient D-2 occupancy may b e sufficient for its antipsychotic effect. Future studies controlling for n onpharmacological effects as well as activities on other receptors will be necessary to confirm this suggestion.