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

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Abstract

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.

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Acknowledgements

We thank Thelma Coutts for assistance with language.

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Author notes

  1. Ilja Spellmann and Matthias A. Reinhard contributed equally.

Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nussbaumstrasse 7, 80336, Munich, Germany

    Ilja Spellmann, Matthias A. Reinhard, Diana Veverka, Peter Zill, Rebecca Schennach, Norbert Müller, Hans-Jürgen Möller, Michael Riedel & Richard Musil

  2. Department of Special Psychiatry, Social Psychiatry and Psychotherapy, Klinikum Stuttgart, Prießnitzweg 24, 70374, Stuttgart, Germany

    Ilja Spellmann

  3. GKM Gesellschaft für Therapieforschung mbH, Lessingstr. 14, 80336, Munich, Germany

    Michael Obermeier

  4. Department of Child and Adolescent Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nussbaumstrasse 5a, 80336, Munich, Germany

    Sandra Dehning

  5. Department of Psychosomatic Medicine, Schön Klinik Roseneck, Roseneck 6, 83209, Prien am Chiemsee, Germany

    Rebecca Schennach

  6. Marion von Tessin Memory-Zentrum gGmbH, Nymphenburgerstrasse. 45, 80335, Munich, Germany

    Norbert Müller

  7. Department of Psychiatry and Psychotherapy, Sächsisches Krankenhaus Rodewisch, Bahnhofstr. 1, 08228, Rodewisch, Germany

    Michael Riedel

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  1. Ilja Spellmann
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Correspondence to Ilja Spellmann.

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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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Spellmann, I., Reinhard, M.A., Veverka, D. et al. QTc prolongation in short-term treatment of schizophrenia patients: effects of different antipsychotics and genetic factors. Eur Arch Psychiatry Clin Neurosci 268, 383–390 (2018). https://doi.org/10.1007/s00406-018-0880-8

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  • DOI: https://doi.org/10.1007/s00406-018-0880-8

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