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- Title
Antipsychotics in routine treatment are minor contributors to QT prolongation compared to genetics and age.
- Authors
Hommers, Leif; Scherf-Clavel, Maike; Stempel, Roberta; Roth, Julian; Falter, Matthias; Deckert, Jürgen; Mattheisen, Manuel; Unterecker, Stefan; Gawlik, Micha
- Abstract
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 (ßstd = 0.176, p < 0.001) and age (ßstd = 0.139, p < 0.001) with the QTc interval corrected according to Fridericia's formula. Sex showed a nominal trend towards significance (ßstd = 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 (ßstd = −0.104, p = 0.010). Haloperidol serum concentrations were associated with the QTc interval only in single medication analysis (n = 26, ßstd = 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.
- Subjects
GENETICS; ANTIPSYCHOTIC agents; ARIPIPRAZOLE; PSYCHIATRIC drugs; DRUG side effects; DRUGS
- Publication
Journal of Psychopharmacology, 2021, Vol 35, Issue 9, p1127
- ISSN
0269-8811
- Publication type
Article
- DOI
10.1177/02698811211003477