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Comparing the Influence of Dopamine D2 Polymorphisms and Plasma Drug Concentrations on the Clinical Response to Risperidone

Yasui-Furukori, Norio MD, PhD; Tsuchimine, Shoko BS; Saito, Manabu MD, PhD; Nakagami, Taku MD, PhD; Sugawara, Norio MD, PhD; Fujii, Akira MD, PhD; Kaneko, Sunao MD, PhD

Journal of Clinical Psychopharmacology: October 2011 - Volume 31 - Issue 5 - p 633-637
doi: 10.1097/JCP.0b013e31822c09a7
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Although several studies have reported that dopamine D2 receptor (DRD2) polymorphisms affect the therapeutic efficacy of antipsychotics, other studies have suggested that the plasma drug concentration is related to the clinical response. Currently, there are no definitive data regarding which factor has greater clinical significance. Sixty patients with acute exacerbations of schizophrenia received 6 mg/d of risperidone for 4 weeks. Clinical evaluations using the Brief Psychiatric Rating Scale and the Udvalg for Klinicke Undersøgelser Side Effect Rating Scale were performed before and after administration of risperidone. TaqI A and −141C Ins/Del polymorphisms were determined, and the plasma concentrations of risperidone and 9-hydroxyrisperidone were measured. The TaqI A polymorphism had no effect on therapeutic efficacy, but the −141C Ins/Del polymorphism was associated with an improvement in positive symptoms. In addition, the plasma concentration of the active moiety (risperidone plus 9-hydroxyrisperidone) correlated with the improvement in the total Brief Psychiatric Rating Scale score as well as with positive symptoms. Although there were no associations between DRD2 polymorphisms and psychic adverse effects, the plasma drug concentration was associated with psychic adverse effects. These findings suggest that DRD2 polymorphisms are associated with the therapeutic effects of risperidone as they relate to positive symptoms and that plasma drug concentrations are associated with overall symptoms as well as excitement and cognitive symptoms. Both the genotyping of DRD2 and the monitoring of plasma drug concentrations may be useful for improving clinically dominant symptoms. Further work involving replication in a larger sample is required to support our findings.

From the Department of Neuropsychiatry, Hirosaki Graduate University, School of Medicine, Hirosaki, Japan.

Received November 24, 2010; accepted after revision April 25, 2011.

Reprints: Norio Yasui-Furukori, MD, PhD, Department of Neuropsychiatry, Hirosaki University, School of Medicine, Hirosaki 036-8562, Japan (e-mail: yasufuru@cc.hirosaki-u.ac.jp).

This study was supported by a grant from the Research Group for Schizophrenia, Japan, and a grant from Hirosaki Research Institute for Neurosciences.

© 2011 Lippincott Williams & Wilkins, Inc.