In vivo determination of striatal dopamine D₂ receptor occupancy in patients treated with olanzapine

In vivo studies of dopamine D₂ receptor occupancy with atypical antipsychotics have suggested good clinical efficacy at occupancy rates less than those observed with typical neuroleptics, and few extrapyramidal side effects (EPS), possibly even at high levels of D₂ occupancy. We used [¹²³I]IBZM-SPECT to investigate striatal D₂ receptor occupancy in 10 schizophrenic patients who were treated with both a low (5 mg) and a high dose (20 mg) of the novel antipsychotic olanzapine without concomitant medications. The mean D₂ occupancy at 5 mg was 59.8% (range 33-81%); the mean D2 occupancy at 20 mg was 82.8% (range 56-97%). Although the D₂ occupancy rates on 5 and 20 mg olanzapine were significantly different (P < 0.001), there were no significant differences in clinical ratings for psychiatric symptoms or extrapyramidal side effects between the two doses of olanzapine. These data suggest that: (1) olanzapine doses below those used routinely occupy D₂ receptors at levels approaching those associated with therapeutic response; (2) higher doses produce relatively high levels of D₂ occupancy rates; and (3) EPS are mild even at relatively high levels of D₂ occupancy.