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

Hans Rasmussen; Bjorn H Ebdrup; David Erritzoe; Bodil Aggernaes; Bob Oranje; Jan Gustav Martin Kalbitzer; Lars H Pinborg; William F C Baaré; Claus Svarer; Henrik Lublin; Gitte Moos Knudsen; Birte Yding Glenthøj

doi:10.1007/s00213-010-1941-5

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

Hans Rasmussen, Bjorn H Ebdrup, David Erritzoe, Bodil Aggernaes, Bob Oranje, Jan Gustav Martin Kalbitzer, Lars H Pinborg, William F C Baaré, Claus Svarer, Henrik Lublin, Gitte Moos Knudsen, Birte Yding Glenthøj

38 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Psychopharmacology
Volume	213
Pages (from-to)	583-592
Number of pages	10
ISSN	0033-3158
DOIs	https://doi.org/10.1007/s00213-010-1941-5
Publication status	Published - Feb 2011

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Rasmussen, H., Ebdrup, B. H., Erritzoe, D., Aggernaes, B., Oranje, B., Kalbitzer, J. G. M., Pinborg, L. H., Baaré, W. F. C., Svarer, C., Lublin, H., Knudsen, G. M., & Glenthøj, B. Y. (2011). Serotonin2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine. Psychopharmacology, 213, 583-592. https://doi.org/10.1007/s00213-010-1941-5

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title = "Serotonin2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine",

abstract = "RATIONALE: We have previously reported decreased frontal cortical serotonin2A receptor binding in 30 antipsychotic na{\"i}ve 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-na{\"i}ve 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-na{\"i}ve 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-na{\"i}ve 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.",

author = "Hans Rasmussen and Ebdrup, {Bjorn H} and David Erritzoe and Bodil Aggernaes and Bob Oranje and Kalbitzer, {Jan Gustav Martin} and Pinborg, {Lars H} and Baar{\'e}, {William F C} and Claus Svarer and Henrik Lublin and Knudsen, {Gitte Moos} and Glenth{\o}j, {Birte Yding}",

year = "2011",

month = feb,

doi = "10.1007/s00213-010-1941-5",

language = "English",

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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 -

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

Abstract

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