Antipsychotics in routine treatment are minor contributors to QT prolongation compared to genetics and age

• Published in: Journal of psychopharmacology (Oxford) 2021-09, Vol.35 (9), p.1127-1133
• Main Authors: Hommers, Leif, Scherf-Clavel, Maike, Stempel, Roberta, Roth, Julian, Falter, Matthias, Deckert, Jürgen, Mattheisen, Manuel, Unterecker, Stefan, Gawlik, Micha
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Age Factors; Aged; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotics; Aripiprazole; Clozapine; Drug interaction; Electrocardiography; Female; Genetic factors; Genotypes; Haloperidol; Humans; Long QT Syndrome - chemically induced; Long QT Syndrome - epidemiology; Long QT Syndrome - genetics; Male; Middle Aged; Multifactorial Inheritance; Olanzapine; Original Papers; Psychotic Disorders - drug therapy; Psychotropic drugs; Quetiapine; Retrospective Studies; Risperidone; Sex Factors; Young Adult
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/02698811211003477

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.