5-HT2 AND D-2 RECEPTOR OCCUPANCY OF OLANZAPINE IN SCHIZOPHRENIA - A PET INVESTIGATION

Objective: Olanzapine is a new atypical antipsychotic recently introdu ced for the treatment of schizophrenia. The purpose of this study was to investigate olanzapine's binding to the serotonin 5-HT2 and dopamin e D-2 receptors in schizophrenic patients being treated with clinicall y relevant doses. Method: Twelve patients with schizophrenia were rand omly assigned to 5, 10, 15, or 20 mg/day of olanzapine in a prospectiv e fashion. Three other subjects taking 30-40 mg/day were also included . Once steady-state plasma levels were achieved, dopamine D-2 and sero tonin 5-HT2 receptors were assessed by using [C-11]raclopride and [F-1 8]setoperone positron emission tomography imaging, respectively. Ratin gs of clinical status, extrapyramidal side effects, and prolactin leve ls were also obtained. Results: Olanzapine induced near saturation of the 5-HT2 receptors, even at 5 mg/day. Its D-2 occupancy increased wit h dose: patients taking 5-20 mg/day showed 43%-80% D-2 occupancy, whil e patients taking 30-40 mg/day showed 83%-88%. Conclusions: Olanzapine is a potent 5-HT2 blocker and shows a higher 5-HT2 than D-2 occupancy at all doses. However, its D-2 occupancy is higher than that of cloza pine and similar to that of risperidone. In the usual clinical dose ra nge of 10-20 mg/day, its occupancy varies from 71% to 80%, and this re stricted range may explain its freedom from extrapyramidal side effect s and prolactin elevation. However, doses of 30 mg/day and higher are associated with more than 80% D-2 occupancy and may have a higher like lihood of prolactin elevation and extrapyramidal side effects.