In vivo determination of striatal dopamine D-2 receptor occupancy in patients treated with olanzapine

In vivo studies of dopamine D-2 receptor occupancy with atypical antipsycho tics have suggested good clinical efficacy at occupancy rates less than tho se observed with typical neuroleptics, and few extrapyramidal side effects (EPS), possibly even at high levels of D-2 occupancy. We used [I-123]IBZM-S PECT to investigate striatal D-2 receptor occupancy in 10 schizophrenic pat ients who were treated with both a low (5 mg) and a high dose (20 mg) of th e novel antipsychotic olanzapine without concomitant medications. The mean D-2 occupancy at 5 mg was 59.8% (range 33-81%); the mean D-2 occupancy at 2 0 mg was 82.8% (range 56-97%). Although the D-2 occupancy rates on 5 and 20 mg olanzapine were significantly different (P < 0.001), there were no sign ificant differences in clinical ratings for psychiatric symptoms or extrapy ramidal side effects between the two doses of olanzapine. These data sugges t that: (1) olanzapine doses below those used routinely occupy D-2 receptor s at levels approaching those associated with therapeutic response; (2) hig her doses produce relatively high levels of D-2 occupancy rates; and (3) EP S are mild even at relatively high levels of D-2 occupancy. (C) 1999 Elsevi er Science Ireland Ltd. All rights reserved.