Open AccessAntipsychotics in routine treatment are minor contributors to QT prolongation compared to genetics and age
Author(s) -
Leif Hommers,
Maike ScherfClavel,
Roberta Stempel,
Julian Roth,
Matthias Falter,
Jürgen Deckert,
Manuel Mattheisen,
Stefan Unterecker,
Micha Gawlik
Publication year - 2021
Publication title -
journal of psychopharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.333
H-Index - 114
eISSN - 1461-7285
pISSN - 0269-8811
DOI - 10.1177/02698811211003477
Subject(s) - qt interval , clozapine , medicine , aripiprazole , quetiapine , olanzapine , antipsychotic , haloperidol , prolongation , risperidone , psychotropic drug , pharmacology , schizophrenia (object oriented programming) , drug , psychiatry , dopamine
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 std = 0.176, p < 0.001) and age (ß std = 0.139, p < 0.001) with the QTc interval corrected according to Fridericia’s formula. Sex showed a nominal trend towards significance (ß std = 0.064, p = 0.064). No association was observed for the number of QT prolonging drugs according to AZCERT taken. Subsample analysis ( n = 588) showed a significant association of potassium serum concentrations with the QTc interval (ß std = −0.104, p = 0.010). Haloperidol serum concentrations were associated with the QTc interval only in single medication analysis ( n = 26, ß std = 0.101, p = 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.