Subjective experience and D2 receptor occupancy in patients with recent-onset schizophrenia treated with low-dose olanzapine or haloperidol: a randomized, double-blind study

Am J Psychiatry. 2003 Feb;160(2):303-9. doi: 10.1176/appi.ajp.160.2.303.


Objective: The authors tested the hypothesis that a dopamine D(2) receptor occupancy level between 60% and 70% in patients with recent-onset schizophrenia would result in optimal subjective experience. In addition, they sought preliminary evidence on whether subjective experience is better with low-dose olanzapine than with low-dose haloperidol.

Method: Subjects (N=24) who met DSM-IV criteria for schizophrenia were randomly assigned to 6 weeks of double-blind treatment with either olanzapine, 7.5 mg/day, or haloperidol, 2.5 mg/day. Subjective experience, psychopathology, and extrapyramidal symptoms were assessed at baseline and at endpoint. After 6 weeks, D(2) receptor occupancy was assessed with [(123)I]iodobenzamide single photon emission computed tomography.

Results: The two study groups were similar at baseline. After 6 weeks, patients receiving olanzapine had a significantly lower mean dopamine D(2) receptor occupancy (51.0%, range=36%-67%) than those given haloperidol (65.5%, range=45%-75%). Receptor occupancy between 60% and 70% was associated with optimal subjective experience, and subjective experience improved significantly in the haloperidol group.

Conclusions: A level of D(2) receptor occupancy between 60% and 70% is optimal for subjective experience of patients with recent-onset schizophrenia. Substantial interindividual variation in D(2) receptor occupancy was seen at fixed low-dose levels of olanzapine and haloperidol. Olanzapine, 7.5 mg/day, showed no superior subjective response over haloperidol, 2.5 mg/day. Olanzapine may need to be dosed higher than 7.5 mg/day for most patients with recent-onset schizophrenia, and haloperidol needs to be individually titrated in the very low dose range to reach optimal occupancy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Basal Ganglia Diseases / chemically induced
  • Benzodiazepines
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Haloperidol / administration & dosage
  • Haloperidol / pharmacology
  • Haloperidol / therapeutic use
  • Humans
  • Iodobenzenes
  • Male
  • Olanzapine
  • Pirenzepine / administration & dosage
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / pharmacology
  • Pirenzepine / therapeutic use
  • Psychiatric Status Rating Scales
  • Receptors, Dopamine D2 / drug effects*
  • Receptors, Dopamine D2 / metabolism*
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism*
  • Schizophrenic Psychology
  • Tomography, Emission-Computed, Single-Photon
  • Treatment Outcome


  • Antipsychotic Agents
  • Iodobenzenes
  • Receptors, Dopamine D2
  • idobenzamide
  • Benzodiazepines
  • Pirenzepine
  • Haloperidol
  • Olanzapine