与遗传和年龄相比，抗精神病药在常规治疗中对 QT 延长的贡献较小。
Antipsychotics in routine treatment are minor contributors to QT prolongation compared to genetics and age.
机构信息
Center for Mental Health, University Hospital of Würzburg, Würzburg, Germany.
Interdisciplinary Center for Clinical Research, University Hospital of Würzburg, Würzburg, Germany.
出版信息
J Psychopharmacol. 2021 Sep;35(9):1127-1133. doi: 10.1177/02698811211003477. Epub 2021 Mar 28.
BACKGROUND
Drug-induced prolongation of cardiac repolarization limits the treatment with many psychotropic drugs. Recently, the contribution of polygenic variation to the individual duration of the QT interval was identified.
AIMS
To explore the interaction between antipsychotic drugs and the individual polygenic influence on the QT interval.
METHODS
Retrospective analysis of clinical and genotype data of 804 psychiatric inpatients diagnosed with a psychotic disorder. The individual polygenic influence on the QT interval was calculated according to the method of Arking et al.
RESULTS
Linear regression modelling showed a significant association of the individual polygenic QT interval score (ß = 0.176, < 0.001) and age (ß = 0.139, < 0.001) with the QTc interval corrected according to Fridericia's formula. Sex showed a nominal trend towards significance (ß = 0.064, = 0.064). No association was observed for the number of QT prolonging drugs according to AZCERT taken. Subsample analysis ( = 588) showed a significant association of potassium serum concentrations with the QTc interval (ß = -0.104, = 0.010). Haloperidol serum concentrations were associated with the QTc interval only in single medication analysis ( = 26, ß = 0.101, = 0.004), but not in multivariate regression analysis. No association was observed for aripiprazole, clozapine, quetiapine and perazine, while olanzapine and the sum of risperidone and its metabolite showed a negative association.
CONCLUSIONS
Individual genetic factors and age are main determinants of the QT interval. Antipsychotic drug serum concentrations within the therapeutic range contribute to QTc prolongation on an individual level.
背景
药物引起的心脏复极延长限制了许多精神药物的治疗。最近，个体 QT 间期的多基因变异对个体 QT 间期的贡献已被确定。
目的
探讨抗精神病药物与个体对 QT 间期的多基因影响之间的相互作用。
方法
对 804 例诊断为精神障碍的住院精神病患者的临床和基因型数据进行回顾性分析。根据 Arking 等人的方法计算个体对 QT 间期的多基因影响。
结果
线性回归模型显示，个体多基因 QT 间期评分（ß=0.176，<0.001）和年龄（ß=0.139，<0.001）与 Fridericia 公式校正的 QTc 间期显著相关。性别呈名义趋势（ß=0.064，=0.064）。根据 AZCERT 计算的 QT 延长药物数量无相关性。子样本分析（=588）显示，血清钾浓度与 QTc 间期呈显著负相关（ß=-0.104，=0.010）。在单一药物分析中，氟哌啶醇血清浓度与 QTc 间期相关（=26，ß=0.101，=0.004），但在多元回归分析中不相关。阿立哌唑、氯氮平、喹硫平、奋乃静无相关性，奥氮平和利培酮及其代谢物总和呈负相关。
结论
个体遗传因素和年龄是 QT 间期的主要决定因素。治疗范围内的抗精神病药物血清浓度在个体水平上导致 QTc 延长。
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