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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436313 | PMC |
| http://dx.doi.org/10.1177/02698811211003477 | DOI Listing |
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