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

Introduction Drug-induced prolongation of cardiac repolarization is a limitation in the treatment of psychiatric disorders with many psychotropic drugs. Recently, the contribution of polygenic variation to the individual duration of the QT interval was identified.

Methods Drug-induced prolongation of cardiac repolarization is a limitation in the treatment of psychiatric disorders with many psychotropic drugs. Recently, the contribution of polygenic variation to the individual duration of the QT interval was identified.

Results Step-wise linear regression modelling revealed a significant association of age (beta = 0.314 ± 0.059; beta(std) = 0.184; p < 0.001), individual genetic duration of the QT interval (beta = 0.959 ± 0.196; beta(std) = 0.164; p < 0.001) and the number of QTc prolonging drugs applied (beta = 1.278 ± 0.582; beta(std) = 0.076; p = 0.028). In the subsample of patients with available electrolyte values (n = 615), an additional significant association was noted for potassium levels (beta = − 4.918 ± 2.318; beta(std) = − 0.082; p = 0.034) instead of the number of QTc prolonging drugs applied. No significant association was observed between drug serum concentration of aripiprazole (n = 55), clozapine (n = 125), haloperidol (n = 41), olanzapine (n = 33), perazine (n = 56), quetiapine (n = 108) or risperidone (n = 104) and QTc with and without correction for age, individual genetic duration of the QT interval, potassium levels and number of QTc prolonging drugs applied.

Conclusion In routine treatment, individual genetic factors and age determine the QTc interval. In the absence of individual risk factors, antipsychotic drug serum concentrations within the therapeutic range represent a low arrhythmogenic hazard.