International Journal of Clinical Pharmacy

, Volume 36, Issue 4, pp 757–765 | Cite as

Frequency of use of QT-interval prolonging drugs in psychiatry in Belgium

  • Eline VandaelEmail author
  • Thomas Marynissen
  • Johan Reyntens
  • Isabel Spriet
  • Joris Vandenberghe
  • Rik Willems
  • Veerle Foulon
Research Article


Introduction Drug-induced QT-prolongation is an established risk factor for Torsade de pointes and sudden cardiac death. The list of QT-prolonging drugs is extensive and includes many drugs commonly used in psychiatry. Aim In this study we performed a cross-sectional analysis of medication profiles to assess the prevalence of drug interactions potentially leading to QT-prolongation. Setting 6 psychiatric hospitals in Flanders, Belgium. Methods For each patient, the full medication list was screened for the presence of interactions, with special attention to those with an increased risk for QT-prolongation. Current practice on QT monitoring and prevention of drug-induced arrhythmia was assessed. Main outcome measure Number of drug interactions with risk of QT-prolongation. Results 592 patients (46 % female; mean age 55.7 ± 17.1 years) were included in the analysis. 113 QT-prolonging interactions were identified in 43 patients (7.3 %). QT-prolonging interactions occurred most frequently with antidepressants (n = 102) and antipsychotics (n = 100). The precautions and follow-up provided by the different institutions when combining QT-prolonging drugs were very diverse. Conclusion Drug combinations that are associated with QT-prolongation are frequently used in the chronic psychiatric setting. Persistent efforts should be undertaken to provide caregivers with clear guidelines on how to use these drugs in a responsible and safe way.


Antidepressants Antipsychotics Belgium Drug-induced QT-prolongation Drug interactions Psychiatry Torsade de pointes 



We would like to thank Delphine Lesage, Tinne Leyssens, Eline Sol, Nathalie Rahier, Pieter Ramaut, Annelies Van Huynegem and Hakima Abasbassi from the department of Pharmaceutical Sciences for their contribution to the data collection and analysis. We also want to thank the pharmacists of the 6 psychiatric institutions for their participation: Johan Reyntens, Sint-Jan hospital; Marc De Vos, Sint-Jan-Baptist hospital; Daniel Vrijders, Zoete Nood Gods hospital, Maria De Voght, Sint-Alexius hospital; Erik Pauwels, Sint-Lucia hospital, and Willy De Boever, Sint-Hieronymus hospital.


This work was supported by unconditional grants from Boston Scientific and Medtronic Belgium. Dr. Willems is supported as a clinical researcher by the Fund for Scientific Research Flanders. PhD-student Eline Vandael is supported by funding of the Belgian government agency for Innovation by Science and Technology (IWT).

Conflicts of interest



  1. 1.
    Josephson M, Wellens HJ. Implantable defibrillators and sudden cardiac death. Circulation. 2004;109:2685–91.PubMedCrossRefGoogle Scholar
  2. 2.
    Myerburg RJ, Kessler KM, Castellanos A. Sudden cardiac death: epidemiology, transient risk, and intervention assessment. Ann Intern Med. 1993;119:1187–97.PubMedCrossRefGoogle Scholar
  3. 3.
    Myerburg RJ, Interian A Jr, Mitrani RM, Kessler KM, Castellanos A. Frequency of sudden cardiac death and profiles of risk. Am J Cardiol. 1997;80:10F–9F.PubMedCrossRefGoogle Scholar
  4. 4.
    van Noord C, Eijgelsheim M, Stricker BH. Drug- and non-drug-associated QT interval prolongation. Br J Clin Pharmacol. 2010;70:16–23.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Drew BJ, Ackerman MJ, Funk M, Gibler WB, Kligfield P, Menon V, et al. Prevention of Torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. J Am Coll Cardiol. 2010;55:934–47.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350:1013–22.PubMedCrossRefGoogle Scholar
  7. 7.
    U.S. Department of Health and Human Services. Guidance for industry: E14 clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. 2005.Google Scholar
  8. 8.
    Davey P. How to correct the QT interval for the effects of heart rate in clinical studies. J Pharmacol Toxicol Methods. 2002;48:3–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Arizona Center for Education and Research on Therapeutics (AZCERT): QT drug lists by risk groups. 2013. (last accessed 19 Dec 2013) (online).
  10. 10.
    De Bruin ML, Pettersson M, Meyboom RH, Hoes AW, Leufkens HG. Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death. Eur Heart J. 2005;26:590–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Straus SM, Sturkenboom MC, Bleumink GS, Dieleman JP, van der Lei J, de Graeff PA, et al. Non-cardiac QTc-prolonging drugs and the risk of sudden cardiac death. Eur Heart J. 2005;26:2007–12.PubMedCrossRefGoogle Scholar
  12. 12.
    Armahizer MJ, Seybert AL, Smithburger PL, Kane-Gill SL. Drug-drug interactions contributing to QT prolongation in cardiac intensive care units. J Crit Care. 2013;28:243–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Jolly K, Gammage MD, Cheng KK, Bradburn P, Banting MV, Langman MJ. Sudden death in patients receiving drugs tending to prolong the QT interval. Br J Clin Pharmacol. 2009;68:743–51.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Ray WA, Chung CP, Murray KT, Hall K, Stein CM. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med. 2009;360:225–35.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Leonard CE, Freeman CP, Newcomb CW, Bilker WB, Kimmel SE, Strom BL, et al. Antipsychotics and the risks of sudden cardiac death and all-cause death: cohort studies in medicaid and dually-eligible medicaid–medicare beneficiaries of five states. J Clin Exp Cardiol. 2013;10:1–9.Google Scholar
  16. 16.
    Beach SR, Celano CM, Noseworthy PA, Januzzi JL, Huffman JC. QTc prolongation, Torsades de Pointes, and psychotropic medications. Psychosomatics. 2013;54:1–13.PubMedCrossRefGoogle Scholar
  17. 17.
    Castro VM, Clements CC, Murphy SN, Gainer VS, Fava M, Weilburg JB, et al. QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ. 2013;346:288.CrossRefGoogle Scholar
  18. 18.
    Leonard CE, Bilker WB, Newcomb C, Kimmel SE, Hennessy S. Antidepressants and the risk of sudden cardiac death and ventricular arrhythmia. Pharmacoepidemiol Drug Saf. 2011;20:903-913.Google Scholar
  19. 19.
    Moller HJ, Seemuller F, Schennach-Wolff R, Stubner S, Ruther E, Grohmann R. History, background, concepts and current use of comedication and polypharmacy in psychiatry. Int J Neuropsychopharmacol. 2013;18:1–14.Google Scholar
  20. 20.
    Seemuller F, Riedel M, Obermeier M, Bauer M, Adli M, Kronmuller K, et al. Outcomes of 1014 naturalistically treated inpatients with major depressive episode. Eur Neuropsychopharmacol. 2010;20:346–55.PubMedCrossRefGoogle Scholar
  21. 21.
    Stubner S, Grohmann R, von SI, Ruther E, Moller HJ, Muller-Oerlinghausen B, et al. Suicidality as rare adverse event of antidepressant medication: report from the AMSP multicenter drug safety surveillance project. J Clin Psychiatry. 2010;71:1293–307.PubMedCrossRefGoogle Scholar
  22. 22.
    Patel MX, Bishara D, Jayakumar S, Zalewska K, Shiers D, Crawford MJ, et al. Quality of prescribing for schizophrenia: evidence from a national audit in England and Wales. Eur Neuropsychopharmacol. 2014;24:499–509.PubMedCrossRefGoogle Scholar
  23. 23.
    Sala M, Vicentini A, Brambilla P, Montomoli C, Jogia JR, Caverzasi E, et al. QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy. Ann Gen Psychiatry. 2005;4:1.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Barnes T, Davison S, Ferrier IN, Howard R, Kerwin R, King DJ, et al. Consensus statement on high-dose antipsychotic medication. London: Royal College of Psychiatrists. 2005.Google Scholar
  25. 25.
    Ames D, Camm J, Cook P, Falkai P, Gury C, Hurley R, et al. Minimizing the risks associated with QTc prolongation in people with schizophrenia. A consensus statement by the Cardiac Safety in Schizophrenia Group. Encephale. 2002;28:552–62.PubMedGoogle Scholar
  26. 26.
    Ozeki Y, Fujii K, Kurimoto N, Yamada N, Okawa M, Aoki T, et al. QTc prolongation and antipsychotic medications in a sample of 1017 patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:401–5.PubMedCrossRefGoogle Scholar
  27. 27.
    Reilly JG, Ayis SA, Ferrier IN, Jones SJ, Thomas SH. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet. 2000;355:1048–52.PubMedCrossRefGoogle Scholar
  28. 28.
    WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD index. 2013. (last accessed 15 Apr 2014) (online).
  29. 29.
    Curtis LH, Ostbye T, Sendersky V, Hutchison S, Allen LaPointe NM, Al-Khatib SM, et al. Prescription of QT-prolonging drugs in a cohort of about 5 million outpatients. Am J Med. 2003;114:135–41.PubMedCrossRefGoogle Scholar
  30. 30.
    Haueis P, Greil W, Huber M, Grohmann R, Kullak-Ublick GA, Russmann S. Evaluation of drug interactions in a large sample of psychiatric inpatients: a data interface for mass analysis with clinical decision support software. Clin Pharmacol Ther. 2011;90:588–96.PubMedCrossRefGoogle Scholar
  31. 31.
    Abarca J, Malone DC, Armstrong EP, Grizzle AJ, Hansten PD, Van Bergen RC, et al. Concordance of severity ratings provided in four drug interaction compendia. J Am Pharm Assoc. 2004;44:136–41.CrossRefGoogle Scholar
  32. 32.
    Vitry AI. Comparative assessment of four drug interaction compendia. Br J Clin Pharmacol. 2007;63:709–14.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Wong CM, Ko Y, Chan A. Clinically significant drug-drug interactions between oral anticancer agents and nonanticancer agents: profiling and comparison of two drug compendia. Ann Pharmacother. 2008;42:1737–48.PubMedCrossRefGoogle Scholar
  34. 34.
    Isaac T, Weissman JS, Davis RB, Massagli M, Cyrulik A, Sands DZ, et al. Overrides of medication alerts in ambulatory care. Arch Intern Med. 2009;169:305–11.PubMedCrossRefGoogle Scholar
  35. 35.
    Weingart SN, Toth M, Sands DZ, Aronson MD, Davis RB, Phillips RS. Physicians’ decisions to override computerized drug alerts in primary care. Arch Intern Med. 2003;163:2625–31.PubMedCrossRefGoogle Scholar
  36. 36.
    Kuperman GJ, Bobb A, Payne TH, Avery AJ, Gandhi TK, Burns G, et al. Medication-related clinical decision support in computerized provider order entry systems: a review. J Am Med Inform Assoc. 2007;14:29–40.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    van der Sijs H, Kowlesar R, Klootwijk AP, Nelwan SP, Vulto AG, van GT. Clinically relevant QTc prolongation due to overridden drug–drug interaction alerts: a retrospective cohort study. Br J Clin Pharmacol. 2009;67:347–54.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Indermitte J, Beutler M, Bruppacher R, Meier CR, Hersberger KE. Management of drug-interaction alerts in community pharmacies. J Clin Pharm Ther. 2007;32:133–42.PubMedCrossRefGoogle Scholar
  39. 39.
    Murphy JE, Forrey RA, Desiraju U. Community pharmacists’ responses to drug–drug interaction alerts. Am J Health Syst Pharm. 2004;61:1484–7.PubMedGoogle Scholar
  40. 40.
    Zivin K, Pfeiffer PN, Bohnert AS, Ganoczy D, Blow FC, Nallamothu BK, et al. Evaluation of the FDA warning against prescribing citalopram at doses exceeding 40 mg. Am J Psychiatry. 2013;170:642–50.PubMedCrossRefGoogle Scholar
  41. 41.
    Narang P, El-Refai M, Parlapalli R, Danilov L, Manda S, Kaur G, et al. Antipsychotic drugs: sudden cardiac death among elderly patients. Psychiatry (Edgmont). 2010;7:25–9.Google Scholar
  42. 42.
    Drezner JA, Ackerman MJ, Cannon BC, Corrado D, Heidbuchel H, Prutkin JM, et al. Abnormal electrocardiographic findings in athletes: recognising changes suggestive of primary electrical disease. Br J Sports Med. 2013;47:153–67.PubMedCrossRefGoogle Scholar
  43. 43.
    Nielsen J, Graff C, Kanters JK, Toft E, Taylor D, Meyer JM. Assessing QT interval prolongation and its associated risks with antipsychotics. CNS Drugs. 2011;25:473–90.PubMedCrossRefGoogle Scholar

Copyright information

© Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014

Authors and Affiliations

  • Eline Vandael
    • 1
    Email author
  • Thomas Marynissen
    • 2
    • 3
  • Johan Reyntens
    • 4
  • Isabel Spriet
    • 1
    • 5
  • Joris Vandenberghe
    • 6
    • 7
  • Rik Willems
    • 2
    • 3
  • Veerle Foulon
    • 1
  1. 1.Department of Pharmaceutical and Pharmacological Sciences, Clinical Pharmacology and PharmacotherapyKU Leuven – University of LeuvenLeuvenBelgium
  2. 2.Department of Cardiovascular SciencesKU Leuven – University of LeuvenLeuvenBelgium
  3. 3.CardiologyUniversity Hospitals LeuvenLeuvenBelgium
  4. 4.Sint-Jan HospitalEekloBelgium
  5. 5.Pharmacy DepartmentUniversity Hospitals LeuvenLeuvenBelgium
  6. 6.Department of NeurosciencesKU Leuven – University of LeuvenLeuvenBelgium
  7. 7.PsychiatryUniversity Hospitals LeuvenLeuvenBelgium

Personalised recommendations