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


METHODS
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.
de Haan
Lieuwe
L
Academic Medical Center, University of Amsterdam Department of Psychiatry, The Netherlands. l.dehaan@amc.uva.nl
van Bruggen
Marion
M
Lavalaye
Jules
J
Booij
Jan
J
Dingemans
Peter M A J
PM
Linszen
Don
D
D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D001569:Benzodiazepines; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007462:Iodobenzenes; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D012565:Schizophrenic Psychology; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D007462:Iodobenzenes; D017448:Receptors, Dopamine D2; C426805:idobenzamide; D001569:Benzodiazepines; D010890:Pirenzepine; D006220:Haloperidol; D000077152:Olanzapine