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Letter to the EditorFull Access

In Vivo Serotonin 5-HT2A Receptor Occupancy and Quetiapine

Published Online:1 Jan 2000https://doi.org/10.1176/ajp.157.1.148

To the Editor: Quetiapine is a novel atypical antipsychotic drug. Clinical studies report a placebo-level incidence of extrapyramidal side effects and efficacy when quetiapine is used to treat the positive and negative symptoms of schizophrenia (1). Quetiapine shows a differential in vivo affinity for D2/5-HT2A receptors, which are thought to be predictive of an atypical antipsychotic profile (2). In vivo, low occupancy of striatal D2 receptors has been reported (3).

We evaluated the in vivo occupancy of 5-HT2A receptors by quetiapine using [123I]5-I-R91150—a novel, highly selective 5-HT2A ligand—for single photon emission computed tomography (SPECT). Two patients with a DSM-IV diagnosis of schizophrenia gave written informed consent before the study began. They had been receiving quetiapine, 300 mg/day, for 7 and 11 weeks, respectively.

Mr. A was a 36-year-old Caucasian man who had previously been treated with haloperidol; he came in for treatment showing marked orofacial dyskinesia. Previously, severe paranoid symptoms had resulted in a 2-year forensic hospital admission after he had been convicted of arson. Mr. A had a Brief Psychiatric Rating Scale score of 24, which did not change with quetiapine treatment. However, his Abnormal Involuntary Movement Scale score decreased from 12 to 4 after 7 weeks of quetiapine treatment.

Mr. B was a 21-year-old Caucasian man who had previously been treated with flupentixol decanoate (40 mg, two per week) for 2 years. This treatment was associated with akathisia, which was controlled with anticholinergic therapy. After he started treatment with quetiapine, both he and his parents reported substantial improvements in his social interaction and peer relations. He obtained part-time work for the first time in 2 years. Ratings were performed before his quetiapine treatment began and on the day of the scan. Mr. B’s score on the Scale for the Assessment of Negative Symptoms was 60, which decreased to 23 after treatment with quetiapine. He showed no objective evidence of extrapyramidal symptoms.

This image acquisition was as previously reported (4). A brain-dedicated SME 810 multidetector scanner for SPECT acquired a whole-brain multislice sequence 120 minutes after an intravenous injection of 180 MBq of [123I]5-I-R91150, when corticocerebellar ratio levels were maximal and stable. Region-of-interest templates were fitted to cortical and cerebellar regions for each scanning sequence (by reference to an average brain atlas) and adjusted for brain size. The ratio of activity in cortical areas relative to those in the cerebellum (an area almost devoid of 5-HT2A receptors) provided a measure of regional specific binding to 5-HT2A receptors over time. The degree of competitive occupancy of 5-HT2A receptors by antipsychotic treatment is reflected in the level of decline in the specific binding ratio in drug-treated individuals relative to those in the drug-free state (4). The frontal cortex/cerebellum ratio for Mr. A was 0.94 and for Mr. B, 1.07. These are clearly lower than the ratio of 1.40 (SD=0.05) that was reported in five drug-free healthy subjects (5) but are somewhat higher than the 0.88 (SD=0.09) and 0.87 (SD=0.09) reported in patients treated with risperidone and clozapine, respectively (4). These novel data suggest significant in vivo cortical 5-HT2A blockade by quetiapine (at doses of 300 mg/day) and are consistent with the high ratio of 5-HT2A/D2 receptor occupancy observed for other atypical antipsychotic drugs.

References

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