Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels

Michael B. Knable, Andreas Heinz, Thomas Raedler, Daniel R. Weinberger

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)91-101
Number of pages11
JournalPsychiatry Research - Neuroimaging
Issue number2
StatePublished - Sep 29 1997
Externally publishedYes


  • Antipsychotics
  • I-123-IBZM
  • Neuroleptics
  • Schizophrenia

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Psychiatry and Mental health


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