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D2 receptor occupancy under recommended and high doses of olanzapine: an iodine-123-iodobenzamide SPECT study

Department of Psychiatry, Ludwigs-Maximilians-Universität München, Nußbaumstrasse 7, 80 336 München, Germany; emeisen{at}psy.med.uni-muenchen.de

S. Dresel

Department of Nuclear Medicine, Ludwigs-Maximilians-University of Munich, Germany

T. Frodl

G. J. E. Schmitt

U. W. Preuss

Department of Psychiatry, Ludwigs-Maximilians-University of Munich, Germany

B. Rossmüller

K. Tatsch

Department of Nuclear Medicine, Ludwigs-Maximilians-University of Munich, Germany

T. Mager

Department of Psychiatry Ludwigs-Maximilians-University of Munich, Germany

K. Hahn

Department of Nuclear Medicine, Ludwigs-Maximilians-University of Munich, Germany

H. -J. Möller

Department of Psychiatry Ludwigs-Maximilians-University of Munich, Germany

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.

Key Words: atypical neuroleptics • dopamine D2 receptor • [123I] IBZM • olanzapine • SPECT

Journal of Psychopharmacology, Vol. 14, No. 4, 364-370 (2000)
DOI: 10.1177/026988110001400405


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