Treatment response to olanzapine and haloperidol and its association with dopamine D receptor occupancy in first-episode psychosis.
OBJECTIVE
Response to typical antipsychotic medication has been associated with achieving a level of striatal dopamine D2 receptor occupancy in the range of 65% to 70%. We undertook this study to determine whether response to the atypical antipsychotic olanzapine occurs at lower levels of D2 receptor occupancy.


METHODS
Eighteen patients who presented with a first episode of psychosis were randomized to receive olanzapine 5 mg daily or haloperidol 2 mg daily in a double-blind design. We acquired positron emission tomography (PET) scans using the D2 ligand [11C]raclopride within the first 15 days of treatment to determine the percentage of D2 receptors occupied by the medication. According to response, dosage was then adjusted to a maximum dosage of 20 mg daily of either drug. PET scans were repeated after 10 to 12 weeks of treatment.


RESULTS
At the first PET scan, the 8 olanzapine-treated patients had significantly lower D2 receptor occupancies (mean 63.4%, SD 7.3) than those observed in the 10 patients treated with haloperidol (mean 73.0%, SD 6.1). When patients were rescanned following dosage adjustment, mean D2 receptor occupancies were greater than 70% in both groups. D2 receptor occupancies did not differ significantly between the olanzapine-treated group (mean 72.0%, SD 5.7) and the haloperidol-treated group (mean 78.7%, SD 7.6).


CONCLUSIONS
These results suggest that, in patients being treated for a first episode of psychosis, olanzapine has its antipsychotic effect at approximately the same levels of D2 receptor occupancy as are achieved with low dosages of haloperidol.
Zipursky
Robert B
RB
Department of Psychiatry, University of Toronto, Ontario. Robert_Zipursky@camh.net
Christensen
Bruce K
BK
Daskalakis
Zafiris
Z
Epstein
Irvin
I
Roy
Paul
P
Furimsky
Ivana
I
Sanger
Todd
T
Kapur
Shitij
S
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D000077152:Olanzapine; D049268:Positron-Emission Tomography; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000523:psychology; D020891:Raclopride; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; D020891:Raclopride; D006220:Haloperidol; D000077152:Olanzapine