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 proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.
Knable
M B
MB
National Institute of Mental Health, Intramural Research Program, Clinical Brain Disorders Branch, Washington, D.C. 20032, USA. knablem@dirpc.nimh.nih.gov
Heinz
A
A
Raedler
T
T
Weinberger
D R
DR
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001480:Basal Ganglia Diseases / Q000139:chemically induced*; D001549:Benzamides; D001921:Brain / Q000187:drug effects; D001931:Brain Mapping; D018492:Dopamine Antagonists; D004359:Drug Therapy, Combination; D005260:Female; D006220:Haloperidol / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D018967:Risperidone / Q000009:adverse effects* / Q000627:therapeutic use; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D001549:Benzamides; D018492:Dopamine Antagonists; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D006220:Haloperidol; D018967:Risperidone