D2 receptor occupancy under recommended and high doses of olanzapine: an iodine-123-iodobenzamide SPECT study.
The aim of this study was to compare the degree of striatal dopamine D2 receptor availability in patients treated with recommended (5-20 mg, mean dose 11.9 +/- 6.3 mg daily) and higher doses (25-40 mg, mean 32.1 +/- 5.6 mg daily) of the novel antipsychotic drug olanzapine by means of [123I] IBZM Single photon emission computed tomography (SPECT). The results were compared to those of a group of 10 untreated, healthy, age- and sex-matched controls. The degree of dopamine D2 receptor occupancy in the patient group was correlated with the presence of extrapyramidal symptoms (EPS). A total of 20 patients who met the DSM III R criteria for schizophrenia or schizoaffective disorder received a clinically effective antipsychotic monotherapy with olanzapine. The mean daily dose of olanzapine ranged from 0.05-0.6 mg/kg body weight. The dopamine D2 receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding expressed as the [STR-BKG]/BKG ratio ranged from 0.13-0.61 (healthy controls 0.95). The D2 receptor availability revealed an exponential dose-response relationship (r = - 0.85, p < 0.001). The frequency of EPS induced by olanzapine was considerably lower. Only one patient, treated with 40 mg olanzapine, suffered from severe EPS symptoms and had to be given biperiden. There were no significant differences in the presence of EPS symptoms between patients with recommended doses and those with higher doses of olanzapine.
Meisenzahl
E M
EM
Departments of Psychiatry, Ludwigs-Maximilians-University of Munich, Germany. emeisen@psy.med.uni-muenchen.de
Dresel
S
S
Frodl
T
T
Schmitt
G J
GJ
Preuss
U W
UW
Rossmüller
B
B
Tatsch
K
K
Mager
T
T
Hahn
K
K
Möller
H J
HJ
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000453:epidemiology; D001549:Benzamides; D001569:Benzodiazepines; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011618:Psychotic Disorders / Q000378:metabolism; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D001549:Benzamides; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; D010890:Pirenzepine; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D000077152:Olanzapine