Department of Neuropsychiatry, Hirosaki Graduate University, School of Medicine, Hirosaki, Japan.
J Clin Psychopharmacol. 2011 Oct;31(5):633-7. doi: 10.1097/JCP.0b013e31822c09a7.
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.
虽然有几项研究报道多巴胺 D₂ 受体 (DRD2) 多态性影响抗精神病药物的治疗效果，但其他研究表明，血浆药物浓度与临床反应有关。目前，关于哪个因素具有更大的临床意义尚无明确数据。60 例精神分裂症急性加重患者接受 6mg/d 的利培酮治疗 4 周。在给予利培酮前后使用简明精神病评定量表和 Udvalg for Klinicke Undersøgelser 副作用评定量表进行临床评估。确定 TaqI A 和-141CIns/Del 多态性，并测量利培酮和 9-羟基利培酮的血浆浓度。TaqI A 多态性对治疗效果没有影响，但-141CIns/Del 多态性与阳性症状的改善有关。此外，活性部分（利培酮加 9-羟基利培酮）的血浆浓度与总简明精神病评定量表评分的改善以及阳性症状相关。虽然 DRD2 多态性与精神不良影响之间没有关联，但血浆药物浓度与精神不良影响有关。这些发现表明，DRD2 多态性与利培酮的治疗效果相关，因为它们与阳性症状有关，而血浆药物浓度与整体症状以及兴奋和认知症状有关。DRD2 基因分型和血浆药物浓度监测都可能有助于改善主要的临床症状。需要进一步的工作，包括在更大的样本中进行复制，以支持我们的发现。
