Serotonin2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine.
BACKGROUND
We have previously reported decreased frontal cortical serotonin2A receptor binding in 30 antipsychotic naïve first-episode schizophrenic patients and a relationship between this binding and positive psychotic symptoms. Until now, no longitudinal studies of serotonin2A receptor in first-episode antipsychotic-naïve schizophrenia patients have reported on the relationship between serotonin2A receptor occupancy and treatment effect after sustained treatment with a specific atypical antipsychotic compound.


OBJECTIVE
Here, we measured serotonin2A receptor occupancy with [(18)F]altanserin PET in 15 first-episode antipsychotic-naïve schizophrenia patients before and after 6 months of quetiapine treatment. Moreover, we investigated possible relationships between clinical efficacy, oral dose, and plasma levels of quetiapine


RESULTS
Significant nonlinear relationships were found between serotonin2A receptor occupancy, quetiapine dose, and plasma concentration. There was a modest effect on positive symptoms up until a serotonin2A receptor occupancy level of approximately 60%. A receptor occupancy level between 60% and 70% appeared to exert the optimal serotonin2A receptor related treatment effect on positive symptoms whereas no additional serotonin2A receptor associated treatment effect was obtained above a receptor occupancy of 70%.


CONCLUSIONS
Taken together, the data point to a therapeutic role of the serotonin2A receptor in the treatment of subgroups of patients with schizophrenia. Specifically, the study indicates a serotonin2A receptor associated therapeutic window on positive symptoms in responding patients in the range between 60% and 70% occupancy in antipsychotic-naïve first-episode schizophrenia. We speculate that non-responding patients need higher dopamine D(2) receptor blockade. Future studies with concurrent measurement of interactions with the dopamine system are, however, warranted to clarify this.
Rasmussen
Hans
H
Center for Neuropsychiatric Schizophrenia Research, Faculty of Health Sciences, Copenhagen University Hospital Glostrup, Copenhagen, Denmark. hans@cnsr.dk
Ebdrup
Bjorn H
BH
Erritzoe
David
D
Aggernaes
Bodil
B
Oranje
Bob
B
Kalbitzer
Jan
J
Pinborg
Lars H
LH
Baaré
William F C
WF
Svarer
Claus
C
Lublin
Henrik
H
Knudsen
Gitte M
GM
Glenthoj
Birte
B
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives; D008137:Longitudinal Studies; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D000069348:Quetiapine Fumarate; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D013997:Time Factors; D055815:Young Adult
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D044402:Receptor, Serotonin, 5-HT2A; D000069348:Quetiapine Fumarate; C071983:altanserin; D007650:Ketanserin