In vivo I-123 IBZM SPECT imaging of striatal dopamine-2 receptor occupancyin schizophrenic patients treated with olanzapine in comparison to clozapine and haloperidol

We investigated the degree of striatal dopamine-2 (D-2) receptor occupancy in six schizophrenic patients receiving clinically effective antipsychotic treatment with olanzapine 10-25 mg/day in comparison to patients treated wi th clozapine 300-600 mg/day (n = 6) or haloperidol 5-20 mg/day (n = 10). I- 123 Iodobenzamide (IBZM) and single photon emission computerized tomography (SPECT) were used for the visualization of striatal D-2 receptors. For the quantification of striatal D-2 receptor occupancy, striatal IBZM binding i n patients treated with antipsychotics was compared to that in untreated he althy controls (n = 8) reported earlier. Olanzapine led to a mean striatal D-2 receptor occupancy rate of 75% (range 63-85). Haloperidol-treated patie nts showed dose-dependently (Pearson r = 0.64; P < 0.05) a significantly hi gher (P < 0.05) mean occupancy rate of 84% (range 67-94). During clozapine treatment, the mean D-2 receptor occupancy of 33% (range < 20-49) was signi ficantly lower than with olanzapine (P < 0.005). The higher striatal D-2 re ceptor occupancy of haloperidol was correlated with the incidence and sever ity of extrapyramidal motor side-effects (EPS). No clinical relevant EPS oc curred during treatment with olanzapine or clozapine. There was no correlat ion between the degree of striatal D-2 receptor occupancy and clinical impr ovement.