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QTc interval in patients with schizophrenia receiving antipsychotic treatment as monotherapy or polypharmacy

Published online by Cambridge University Press:  29 June 2017

Anja Elliott ,
Thibault Johan Mørk ,
Mikkel Højlund ,
Thomas Christensen ,
Rasmus Jeppesen ,
Nikolaj Madsen ,
Anne Grethe Viuff ,
Peter Hjorth ,
Jens Cosedis Nielsen  and
Povl Munk-Jørgensen
Anja Elliott*
Affiliation:
Aarhus University Hospital, Department of Affective Disorders, Risskov, Denmark Psychiatric Research Academy, Psychiatric Hospital and University of Southern Denmark, Odense, Denmark
Thibault Johan Mørk
Affiliation:
Department of Cardiology, Aarhus University Hospital–Skejby, Skejby, Denmark
Mikkel Højlund
Affiliation:
Aarhus University Hospital, Department of Affective Disorders, Risskov, Denmark Psychiatric Research Academy, Psychiatric Hospital and University of Southern Denmark, Odense, Denmark
Thomas Christensen
Affiliation:
Aarhus University Hospital, Department of Affective Disorders, Risskov, Denmark
Rasmus Jeppesen
Affiliation:
Aarhus University Hospital, Department of Affective Disorders, Risskov, Denmark
Nikolaj Madsen
Affiliation:
Aarhus University Hospital, Department of Affective Disorders, Risskov, Denmark
Anne Grethe Viuff
Affiliation:
Department of Psychiatry, Regional Psychiatry West, Herning, Denmark
Peter Hjorth
Affiliation:
Aarhus University Hospital, Department of Affective Disorders, Risskov, Denmark Regional Psychiatry Services, Randers, Denmark Department of Regional Health Research, University of Southern Denmark, Odense, Denmark
Jens Cosedis Nielsen
Affiliation:
Department of Cardiology, Aarhus University Hospital–Skejby, Skejby, Denmark
Povl Munk-Jørgensen
Affiliation:
Aarhus University Hospital, Department of Affective Disorders, Risskov, Denmark Psychiatric Research Academy, Psychiatric Hospital and University of Southern Denmark, Odense, Denmark
*
*Address correspondence to: Anja Elliott, Department of Affective Disorders, Aarhus University Hospital, Risskov, Denmark, and University of Southern Denmark, Skovagervej 2, 8240 Odense, Denmark. (Email: [email protected])
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Abstract

Objective

Antipsychotics are associated with a polymorphic ventricular tachycardia, torsades de pointes, which, in the worst case, can lead to sudden cardiac death. The QT interval corrected for heart rate (QTc) is used as a clinical proxy for torsades de pointes. The QTc interval can be prolonged by antipsychotic monotherapy, but it is unknown if the QTc interval is prolonged further with antipsychotic polypharmaceutical treatment. Therefore, this study investigated the associations between QTc interval and antipsychotic monotherapy and antipsychotic polypharmaceutical treatment in schizophrenia, and measured the frequency of QTc prolongation among patients.

Methods

We carried out an observational cohort study of unselected patients with schizophrenia visiting outpatient facilities in the region of Central Jutland, Denmark. Patients were enrolled from January of 2013 to June of 2015, with follow-up until June of 2015. Data were collected from clinical interviews and clinical case records.

Results

Electrocardiograms were available for 65 patients, and 6% had QTc prolongation. We observed no difference in average QTc interval for the whole sample of patients receiving no antipsychotics, antipsychotic monotherapy, or antipsychotic polypharmaceutical treatment (p=0.29). However, women presented with a longer QTc interval when receiving polypharmacy than when receiving monotherapy (p=0.01). A limitation of this study was its small sample size.

Conclusions

We recommend an increased focus on monitoring the QTc interval in women with schizophrenia receiving antipsychotics as polypharmacy.

Keywords

QTcpolypharmacyantipsychoticsschizophreniasex difference
Type
Original Research
Information
CNS Spectrums , Volume 23 , Issue 4 , August 2018 , pp. 278 - 283
Copyright
© Cambridge University Press 2017 

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References

1. Hou, PY, Hung, GC, Jhong, JR, Tsai, SY, Chen, CC, Kuo, CJ. Risk factors for sudden cardiac death among patients with schizophrenia. Schizophr Res. 2015; 168(1–2): 395–401.Google Scholar
2. Hennessy, S, Bilker, WB, Knauss, JS, et al. Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data. BMJ. 2002; 325(7372): 1070.Google Scholar
3. Straus, SM, Bleumink, GS, Dieleman, JP, et al. Antipsychotics and the risk of sudden cardiac death. Arch Intern Med. 2004; 164(12): 1293–1297.Google Scholar
4. Glassman, AH, Bigger, J. Antipsychotic drugs: Prolonged QTc interval, torsade de pointes, and sudden death. Am J Psychiatry. 2001; 158(11): 1774–1782.Google Scholar
5. Fermini, B, Fossa, AA. The impact of drug-induced QT interval prolongation on drug discovery and development. Nat Rev Drug Discov. 2003; 2(6): 439–447.Google Scholar
6. Leucht, S, Cipriani, A, Spineli, L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013; 382(9896): 951–962.Google Scholar
7. Hasnain, M, Vieweg, WV. QTc interval prolongation and torsade de pointes associated with second-generation antipsychotics and antidepressants: a comprehensive review. CNS Drugs. 2014; 28(10): 887–920.Google Scholar
8. Barnes, TR, Paton, C. Antipsychotic polypharmacy in schizophrenia: benefits and risks. CNS Drugs. 2011; 25(5): 383–399.Google Scholar
9. Barbui, C, Bighelli, I, Carrà, G, et al. Antipsychotic dose mediates the association between polypharmacy and corrected QT interval. PLoS One. 2016; 11(4): 1–12.Google Scholar
10. Nosè, M, Bighelli, I, Castellazzi, M, et al. Prevalence and correlates of QTc prolongation in Italian psychiatric care: cross-sectional multicentre study. Epidemiol Psychiatr Sci. 2015; 25(6): 532–540.Google Scholar
11. Takeuchi, H, Suzuki, T, Remington, G, Uchida, H. Antipsychotic polypharmacy and corrected QT interval: a systematic review. Can J Psychiatry. 2015; 60(5): 215–222.Google Scholar
12. Hansen, MV, Hjorth, P, Kristiansen, CB, Vandborg, K, Gustafsson, LN, Munk-Jørgensen, P. Reducing cardiovascular risk factors in non-selected outpatients with schizophrenia. Int J Soc Psychiatry. 2016; 62(4): 369–376.Google Scholar
13. World Health Organization. The ICD–10 Classification of Mental and Behavioural Disorders. Geneva: World Health Organization; 1993. http://www.who.int/classifications/icd/en/bluebook.pdf. Accessed June 4, 2017.Google Scholar
14. Petersen, L, Jeppesen, P, Thorup, A, et al. A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness. BMJ. 2005; 331(7517): 602.Google Scholar
15. World Health Organization. Introduction to Drug Utilization Research, 2nd ed. Geneva: World Health Organization; 2003. http://apps.who.int/medicinedocs/pdf/s4876e/s4876e.pdf. Accessed June 4, 2017.Google Scholar
16. Forlænget QTc. Copenhagen: Danish Society for Clinical Psychopharmacology; 2013. http://www.psykofarmakologi.dk/resources/actioncards/ac_pdfs/ForlaengetQTc.pdf. Accessed June 4, 2017.Google Scholar
17. Goldenberg, I, Moss, AJ, Zareba, W. QT interval: how to measure it and what is “normal”. J Cardiovasc Electrophysiol. 2006; 17(3): 333–337.Google Scholar
18. Schwartz, PJ, Moss, AJ, Vincent, GM, Crampton, RS. Diagnostic criteria for the long QT syndrome: an update. Circulation. 1993; 88(2): 782–785.Google Scholar
19. Goldenberg, I, Horr, S, Moss, AJ, et al. Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals. J Am Coll Cardiol. 2011; 57(1): 51–59.Google Scholar
20. Fanoe, S, Kristensen, D, Fink-Jensen, A, et al. Risk of arrhythmia induced by psychotropic medications: a proposal for clinical management. Eur Heart J. 2014; 35(20): 1306–1315.Google Scholar
21. Ramos-Ríos, R, Arrojo-Romero, M, Paz-Silva, E, et al. QTc interval in a sample of long-term schizophrenia inpatients. Schizophr Res. 2010; 116(1): 35–43.Google Scholar
22. Pasquier, M, Pantet, O, Hugli, O, et al. Prevalence and determinants of QT interval prolongation in medical inpatients. Intern Med J. 2012; 42(8): 933–940.Google Scholar
23. Yang, FD, Wang, XQ, Liu, XP, et al. Sex difference in QTc prolongation in chronic institutionalized patients with schizophrenia on long-term treatment with typical and atypical antipsychotics. Psychopharmacology (Berl). 2011; 216(1): 9–16.Google Scholar
24. Rabkin, SW. Impact of age and sex on QT prolongation in patients receiving psychotropics. Can J Psychiatry. 2015; 60(5): 206–214.Google Scholar
25. Haddad, PM, Anderson, IM. Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs. 2002; 62(11): 1649–1671.Google Scholar