Double-blind olanzapine vs. haloperidol D2 dopamine receptor blockade in schizophrenic patients: a baseline-endpoint [I-123]IBZM SPECT study

The aim of this study was to compare in vivo striatal D2 dopamine receptor occupancy induced by olanzapine and haloperidol in schizophrenic patients u sing a baseline-endpoint [I-123]IBZM single photon computed emission tomogr aphy (SPECT) design. The relationships of striatal D2 receptor occupancy wi th clinical efficacy and extrapyramidal symptoms (EPS) were also assessed. Twenty-seven inpatients with schizophrenia or schizophreniform. disorder we re included in a 4-week prospective, randomized, double-blind, parallel and comparative clinical trial. Thirteen patients were treated with haloperido l (10 mg/day) and 14 with olanzapine (10 mg/day). Ratings of clinical statu s and EPS were obtained weekly. The percentage of D2 receptor occupancy was estimated by using basal ganglia (striatum)/frontal cortex IBZM uptake rat ios obtained from each patient before and after 4 weeks of maintained antip sychotic treatment. Olanzapine led to a mean striatal D2 receptor occupancy of 49% (range 28-69%), which was significantly lower than that induced by haloperidol (mean 64%, range 46-90%). The baseline-endpoint SPECT design us ed in this study revealed lower antipsychotic D2 occupancy percentage value s than those reported in the literature, using other approaches. The degree of striatal D2 receptor occupancy correlated to the EPS, which predominant ly appeared in patients on haloperidol. No relationship was found between t he striatal D2 receptor occupancy and clinical improvement. Olanzapine indu ced a lower striatal D2 occupancy than haloperidol. This low striatal D2 oc cupancy, together with the lower incidence of EPS in olanzapine-treated pat ients, contributed to confirm the atypical behavior of this now antipsychot ic drug. Nevertheless, conclusions based on SPECT-estimated percentages of antipsychotic D2 occupancy should be cautious, since the SPECT design could influence the results. In this regard, SPECT studies including baseline an d endpoint examinations should be encouraged. (C) 2001 Elsevier Science Ire land Ltd. All rights reserved.