Serotonin2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine

TY - JOUR

T1 - Serotonin2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine

AU - Rasmussen, Hans

AU - Ebdrup, Bjorn H

AU - Erritzoe, David

AU - Aggernaes, Bodil

AU - Oranje, Bob

AU - Kalbitzer, Jan Gustav Martin

AU - Pinborg, Lars H

AU - Baaré, William F C

AU - Svarer, Claus

AU - Lublin, Henrik

AU - Knudsen, Gitte Moos

AU - Glenthøj, Birte Yding

PY - 2011/2

Y1 - 2011/2

N2 - RATIONALE: 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. OBJECTIVES: 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.

AB - RATIONALE: 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. OBJECTIVES: 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.

U2 - 10.1007/s00213-010-1941-5

DO - 10.1007/s00213-010-1941-5

M3 - Journal article

C2 - 20614105

SN - 0033-3158

VL - 213

SP - 583

EP - 592

JO - Psychopharmacology

JF - Psychopharmacology

ER -