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 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.

• Authors: Hans Rasmussen, Bjorn H Ebdrup, David Erritzoe, Bodil Aggernaes, Bob Oranje, Jan Kalbitzer, Lars H Pinborg, William F C Baaré, Claus Svarer, Henrik Lublin, Gitte M Knudsen, Birte Glenthoj
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 213 Issue 2-3 Pg. 583-92 (Feb 2011) ISSN: 1432-2072 [Electronic] Germany
• PMID: 20614105 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antipsychotic Agents
• Dibenzothiazepines
• Receptor, Serotonin, 5-HT2A
• Quetiapine Fumarate
• altanserin
• Ketanserin

Topics

• Adult
• Antipsychotic Agents (administration & dosage, pharmacokinetics, pharmacology)
• Dibenzothiazepines (administration & dosage, pharmacokinetics, pharmacology)
• Dose-Response Relationship, Drug
• Female
• Follow-Up Studies
• Humans
• Ketanserin (analogs & derivatives)
• Longitudinal Studies
• Male
• Positron-Emission Tomography (methods)
• Quetiapine Fumarate
• Receptor, Serotonin, 5-HT2A (drug effects, metabolism)
• Schizophrenia (drug therapy, physiopathology)
• Schizophrenic Psychology
• Time Factors
• Young Adult