Comparing the Influence of Dopamine D2 Polymorphisms and Plasma Drug Concentrations on the Clinical Response to Risperidone
Comparing the Influence of Dopamine D2 Polymorphisms and Plasma Drug Concentrations on the Clinical Response to Risperidone
复制标题
比较多巴胺 D2 多态性和血浆药物浓度对利培酮临床反应的影响
DOI：
10.1097/jcp.0b013e31822c09a7
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发表时间：
2011
影响因子：
2.9
通讯作者：
S. Kaneko
中科院分区：
文献类型：
--
作者：
N. Yasui‐Furukori;S. Tsuchimine;M. Saito;T. Nakagami;Norio Sugawara;A. Fujii;S. Kaneko
虽然一些研究报道多巴胺D2受体（DRD 2）多态性影响抗精神病药物的疗效，但其他研究表明血浆药物浓度与临床反应有关。目前，还没有确切的数据表明哪种因素具有更大的临床意义。60例精神分裂症急性加重期患者接受利培酮6 mg/d治疗4周。在利培酮给药前后，使用简明精神病评定量表和Klinicke Undersøgelser副作用评定量表进行临床评价。测定TaqI A和− 141 C Ins/Del多态性，并测定利培酮和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− 141 C Ins/Del多态性与阳性症状的改善相关。此外，活性成分（利培酮+9-羟基利培酮）的血浆浓度与简明精神病评定量表总分的改善以及阳性症状相关。虽然DRD 2基因多态性与精神不良反应之间没有关联，但血浆药物浓度与精神不良反应相关。这些研究结果表明，DRD 2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，血浆药物浓度与总体症状以及兴奋和认知症状相关。DRD 2基因分型和血药浓度监测可能有助于改善临床显性症状。需要进一步的工作，涉及在更大的样本复制，以支持我们的研究结果。
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.
影响因子：
17.7
作者：
Lencz, T;Robinson, DG;Malhotra, AK
通讯作者：
Malhotra, AK
DOI：
--
发表时间：
1996
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
J. Lieberman;A. Koreen;M. Chakos;B. Sheitman;M. Woerner;J. Alvir;R. Bilder
通讯作者：
J. Lieberman;A. Koreen;M. Chakos;B. Sheitman;M. Woerner;J. Alvir;R. Bilder