D2 receptor occupancy in risperidone and clozapine-treated schizophrenics

Risperidone and clozapine are atypical neuroleptics for the treatment of schizophrenia. We have previously reported that wide ranges of D2 occupancies (18 − ≥ 80%) are associated with favorable response to clozapine without the occurrence of extrapyramidal symptom (EPS) (Su et al 1993). Risperidone has been found to produce high levels of D2 blockade without EPS (Busatto et al 1995). The specific aim of this study is to compare D2 occupancy between risperidone and clozapine in chronic schizophrenics and to determine the relationship of clinical efficacy and EPS to D2 occupancy. We have examined this issue with two separate studies. In study 1, five schizophrenics underwent IBZM-SPECT scanning during treatment with clozapine (400mg/day) and with risperidone (6mg/day) in a double-blind, crossover fashion. In study 2 (double-blind), 7 patients on risperidone (4-8 mg/day) and 7 patients on clozapine (175 mg-600mg/day) matched for age, sex, and illness severity were scanned. Despite similar clinical efficacy, risperidone resulted in significantly higher D2 occupancy (study 1: 77 ± 6%, study 2: 71 ± 6%) than clozapine (study 1: 52 ± 8%, study 2: 39 ± 12%) (t4 = 5.5 and t12 = 6.4 respectively, p < 0.005). While clozapine - treated patients did not display EPS, 8 of 12 patients on risperidone did have modest EPS (Simpson Neurological Rating: 13.6 ± 1.4). The other 4 patients were free of EPS even with high level of D2 occupancy (65-81%). These 81%). These data confirm that risperidone is a more potent D2 blocker than clozapine and suggest that clinical efficacy and EPS are not simply related to D2 occupancy, but may involve other neurotransmitter systems.