EXTRAPYRAMIDAL SIDE-EFFECTS WITH RISPERIDONE AND HALOPERIDOL AT COMPARABLE D2 RECEPTOR OCCUPANCY LEVELS

Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have propose d that risperidone's pharmacologic profile may produce improved effica cy for negative psychotic symptoms and decreased propensity for extrap yramidal side effects; features shared by so-called 'atypical' neurole ptics. To determine if routine risperidone treatment is associated wit h a unique degree of D2 receptor occupancy and pattern of clinical eff ects, we used [I-123]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloper idol (n = 7). Both risperidone and haloperidol produced D2 occupancy l evels between approximately 60 and 90% at standard clinical doses. The re was no significant difference between occupancy levels obtained wit h haloperidol or risperidone. Drug-induced parkinsonism was observed i n subjects treated with risperidone (42%) and haloperidol (29%) and wa s observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 o ccupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects. (C) 1997 Elsevier Science Irela nd Ltd.