High 5-HT2 receptor occupancy in clozapine treated patients demonstrated by PET

The clinical benefit of the atypical antipsychotic drug clozapine may be related to a combined effect on D₂ and 5-HT₂ receptors. To examine the basis for this hypothesis, positron emission tomography (PET) and the radioligand ¹¹C]N-methylspiperone were used to determine cortical 5-HT₂ receptor occupancy in three psychotic patients treated with 125 mg, 175 mg and 200 mg clozapine daily. The uptake of ¹¹C]N-methylspiperone in the frontal cortex was very low compared to that in neuroleptic naive schizophrenic patients. 5-HT₂ receptor occupancy calculated in the clozapine treated patients was 84%, 87% and 90%. The results show that clinical treatment with clozapine induces a high 5-HT₂ receptor occupancy in psychotic patients at a low dose level.