1. ¹Department of Radiology, Vanderbilt University of School of Medicine, Nashville, TN, USA
2. ²Department of Psychiatry, Vanderbilt University of School of Medicine, Nashville, TN, USA
3. ³Department of Electrical Engineering and Computer Science, Vanderbilt University School of Engineering, Nashville, TN, USA

Correspondence: Dr RM Kessler, Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, 1161 21st Avenue South, Suitr CCC-1121 MCN, Nashville, TN 37232-2675, USA. Tel: +1 615 343 3938; Fax: +1 615 343 6531; E-mail: robert.kessler@vanderbilt.edu

Received 8 November 2004; Revised 25 March 2005; Accepted 9 June 2005; Published online 3 August 2005.

Abstract

There have been conflicting reports as to whether olanzapine produces lower occupancy of striatal dopamine D₂/D₃ receptor than typical antipsychotic drugs and preferential occupancy of extrastriatal dopamine D₂/D₃ receptors. We performed [¹⁸F] fallypride PET studies in six schizophrenic subjects treated with olanzapine and six schizophrenic subjects treated with haloperidol to examine the occupancy of striatal and extrastriatal dopamine receptors by these antipsychotic drugs. [¹⁸F] setoperone PET studies were performed in seven olanzapine-treated subjects to determine 5-HT_2A receptor occupancy. Occupancy of dopamine D₂/D₃ receptors by olanzapine was not significantly different from that seen with haloperidol in the putamen, ventral striatum, medial thalamus, amygdala, or temporal cortex, that is, 67.5–78.2% occupancy; olanzapine produced no preferential occupancy of dopamine D₂/D₃ receptors in the ventral striatum, medial thalamus, amygdala, or temporal cortex. There was, however, significantly lower occupancy of substantia nigra/VTA dopamine D₂/D₃ receptors in olanzapine-treated compared to haloperidol-treated subjects, that is, 40.2 vs 59.3% (p=0.0014, corrected for multiple comparisons); in olanzapine-treated subjects, the substantia nigra/VTA was the only region with significantly lower dopamine D₂/D₃ receptor occupancy than the putamen, that is, 40.2 vs 69.2% (p<0.001, corrected for multiple comparison). Occupancy of 5-HT_2A receptors was 85–93% in the olanzapine- treated subjects. The results of this study demonstrated that olanzapine does not produce preferential occupancy of extrastriatal dopamine D₂/D₃ receptors but does spare substantia nigra/VTA receptors. Sparing of substantia nigra/VTA dopamine D₂/D₃ receptor occupancy may contribute to the low incidence of extrapyramidal side effects in olanzapine-treated patients.