• antipsychotic;
  • dopamine;
  • epidepride;
  • receptor occupancy;
  • schizophrenia

Aims:  Aberrant dopamine transmission in extrastriatal brain regions has been repeatedly illustrated among patients with schizophrenia. Differences between typical and second-generation antipsychotics in dopamine D2 receptor modulation within various brain areas remain a topic for debate. The aim of the present study was therefore to investigate dopamine D2/3 receptor apparent binding potential (BPapp) and occupancy in midbrain and temporal cortex among clozapine-, olanzapine- and haloperidol-treated schizophrenia patients.

Methods:  Dopamine D2/3 binding was studied on single-photon emission computed tomography ligand [123I]epidepride in 13 schizophrenia patients treated with medication (two with haloperidol, four with olanzapine and seven with clozapine), six drug-naïve patients and seven healthy controls.

Results:  Statistically significant differences in midbrain dopamine D2/3 receptor BPapp (P = 0.015) and occupancy (P = 0.016) were observed between the clozapine, olanzapine and haloperidol groups. The lowest occupancy was found in clozapine-treated patients (5%), followed by olanzapine-treated patients (28%), compared to haloperidol-treated patients (40%). No significant differences were observed in the temporal poles. Occupancy changed substantially depending on the comparison group used (either drug-naïve vs healthy controls) in the examined brain areas (P = 0.001), showing an overestimation with all antipsychotics when the healthy control group was used.

Conclusion:  Both typical and second-generation antipsychotics occupy cortical dopamine D2/3 receptors, thus mediating therapeutic efficacy. Observed differences in midbrain dopamine D2/3 occupancy between classical antipsychotics and second-generation antipsychotics may have clinical relevance by modulating altered nigrostriatal dopamine neurotransmission during the acute phase of schizophrenia.