QTc prolongation in short-term treatment of schizophrenia patients: effects of different antipsychotics and genetic factors

  • Ilja Spellmann
  • Matthias A. Reinhard
  • Diana Veverka
  • Peter Zill
  • Michael Obermeier
  • Sandra Dehning
  • Rebecca Schennach
  • Norbert Müller
  • Hans-Jürgen Möller
  • Michael Riedel
  • Richard Musil
Original Paper


Antipsychotics are effective in treating schizophrenia but may lead to a higher cardiovascular risk due to QTc prolongation. Besides drugs, genetic and clinical factors may contribute to QTc prolongation. The aim of this study is to examine the effect of candidate genes known for QTc prolongation and their interaction with common antipsychotics. Thus, 199 patients were genotyped for nine polymorphisms in KCNQ1, KCNH2, SCN5A, LOC10537879, LOC101927066, NOS1AP and NUBPL. QTc interval duration was measured before treatment and weekly for 5 weeks while being treated with risperidone, quetiapine, olanzapine, amisulpride, aripiprazole and haloperidol in monotherapy. Antipsychotics used in this study showed a different potential to affect the QTc interval. We found no association between KCNH2, KCNQ1, LOC10537879, LOC101927066, NOS1AP and NUBPL polymorphisms and QTc duration at baseline and during antipsychotic treatment. Mixed general models showed a significant overall influence of SCN5A (H558R) on QTc duration but no significant interaction with antipsychotic treatment. Our results do not provide evidence for an involvement of candidate genes for QTc duration in the pathophysiology of QTc prolongation by antipsychotics during short-term treatment. Further association studies are needed to confirm our findings. With a better understanding of these interactions the cardiovascular risk of patients may be decreased.


QTc prolongation Atypical antipsychotics Schizophrenia Pharmacogenetics Short-term tolerability 



We thank Thelma Coutts for assistance with language.

Compliance with ethical standards

Conflict of interest

The authors declare that over the past three years Author Dr. R. Musil has received research support from Janssen-Cilag, Speaker Honoraria from Otsuka and has been on the advisory board of Roche Pharmaceuticals, author Prof. Dr. M. Riedel has received grants/research support from AstraZeneca and Pfizer and is speaker or in the advisory board of AstraZeneca, Pfizer, Bristol-Meyers-Squibb, Otsuka and Servier. These affiliations have no relevance to the work covered in the manuscript. On behalf of all authors, the corresponding author states that there is no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Ilja Spellmann
    • 1
    • 2
  • Matthias A. Reinhard
    • 1
  • Diana Veverka
    • 1
  • Peter Zill
    • 1
  • Michael Obermeier
    • 3
  • Sandra Dehning
    • 4
  • Rebecca Schennach
    • 1
    • 5
  • Norbert Müller
    • 1
    • 6
  • Hans-Jürgen Möller
    • 1
  • Michael Riedel
    • 1
    • 7
  • Richard Musil
    • 1
  1. 1.Department of Psychiatry and PsychotherapyLudwig-Maximilians-University MunichMunichGermany
  2. 2.Department of Special Psychiatry, Social Psychiatry and PsychotherapyKlinikum StuttgartStuttgartGermany
  3. 3.GKM Gesellschaft für Therapieforschung mbHMunichGermany
  4. 4.Department of Child and Adolescent Psychiatry and PsychotherapyLudwig-Maximilians-University MunichMunichGermany
  5. 5.Department of Psychosomatic MedicineSchön Klinik RoseneckPrien am ChiemseeGermany
  6. 6.Marion von Tessin Memory-Zentrum gGmbHMunichGermany
  7. 7.Department of Psychiatry and PsychotherapySächsisches Krankenhaus RodewischRodewischGermany

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