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

M B Knable1, A Heinz, T Raedler

  • 1National Institute of Mental Health, Intramural Research Program, Clinical Brain Disorders Branch, Washington, D.C. 20032, USA. knablem@dirpc.nimh.nih.gov

Psychiatry Research
|November 14, 1997
PubMed
Summary

Risperidone and haloperidol equally occupy dopamine D2 receptors at standard doses. Risperidone

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Area of Science:

  • Neuroscience
  • Psychopharmacology
  • Radiopharmaceutical Imaging

Background:

  • Risperidone, an antipsychotic, targets dopamine D2 and serotonin 5-HT2 receptors.
  • It's hypothesized to offer better negative symptom efficacy and fewer extrapyramidal side effects (EPS) than typical neuroleptics.
  • This study investigates risperidone's D2 receptor occupancy and clinical effects compared to haloperidol.

Purpose of the Study:

  • To quantify dopamine D2 receptor occupancy by risperidone and haloperidol using [123I]IBZM SPECT.
  • To correlate D2 receptor occupancy with the incidence of drug-induced parkinsonism.
  • To evaluate if 5-HT2 receptor blockade mitigates EPS at significant D2 occupancy levels.

Main Methods:

  • Positron emission tomography (PET) with [123I]IBZM SPECT was used to measure D2 receptor occupancy.

Related Experiment Videos

  • 12 subjects received routine risperidone doses, and 7 received haloperidol.
  • Clinical assessments for drug-induced parkinsonism were performed.

    • Main Results:

    • Both risperidone and haloperidol achieved 60-90% D2 receptor occupancy at standard clinical doses.
    • No significant difference in D2 occupancy was found between the two drugs.
    • Drug-induced parkinsonism occurred in 42% of risperidone-treated and 29% of haloperidol-treated subjects at >60% D2 occupancy.

    Conclusions:

    • Risperidone and haloperidol exhibit comparable D2 receptor occupancy at equivalent clinical doses.
    • 5-HT2 receptor blockade by risperidone does not prevent extrapyramidal side effects at D2 occupancy levels of 60% or higher.
    • The risk of parkinsonism is present with both agents at substantial D2 receptor occupancy.