Browse > Article
http://dx.doi.org/10.22537/jksct.2020.18.2.66

QTc Prolongation due to Psychotropic Drugs Intoxication and Its Risk Assessment  

Park, Kwan Ho (Department of Emergency Medicine, Kyung Hee University Hospital)
Hong, Hoon Pyo (Department of Emergency Medicine, Kyung Hee University Hospital)
Lee, Jong Seok (Department of Emergency Medicine, Kyung Hee University Hospital)
Jeong, Ki Young (Department of Emergency Medicine, Kyung Hee University Hospital)
Ko, Seok Hun (Department of Emergency Medicine, Kyung Hee University Hospital)
Kim, Sung Kyu (Department of Emergency Medicine, Kyung Hee University Hospital)
Choi, Han Sung (Department of Emergency Medicine, Kyung Hee University Hospital)
Publication Information
Journal of The Korean Society of Clinical Toxicology / v.18, no.2, 2020 , pp. 66-77 More about this Journal
Abstract
Purpose: The aims of the present study were twofold. First, the research investigated the effect of an individual's risk factors and the prevalence of psychotropic drugs on QTc prolongation, TdP (torsades de pointes), and death. Second, the study compared the risk scoring systems (the Mayo Pro-QT risk score and the Tisadale risk score) on QTc prolongation. Methods: The medical records of intoxicated patients who visited the emergency department between March 2010 and February 2019 were reviewed retrospectively. Among 733 patients, the present study included 426 psychotropic drug-intoxicated patients. The patients were categorized according to the QTc value. The known risk factors of QTc prolongation were examined, and the Mayo Pro-QT risk score and the Tisadale risk score were calculated. The analysis was performed using multiple logistic regression, Spearman correlation, and ROC (receiver operating characteristic). Results: The numbers in the mild to moderate group (male: 470≤QTc<500 ms, female: 480≤QTc<500 ms) and severe group (QTc≥500 ms or increase of QTc at least 60ms from baseline, both sex) were 68 and 95, respectively. TdP did not occur, and the only cause of death was aspiration pneumonia. The statically significant risk factors were multidrug intoxications of TCA (tricyclic antidepressant), atypical antipsychotics, an atypical antidepressant, panic disorder, and hypokalemia. The Tisadale risk score was larger than the Mayo Pro-QT risk score. Conclusion: Multiple psychotropic drugs intoxication (TCA, an atypical antidepressant, and atypical antipsychotics), panic disorder, and hypokalemia have been proven to be the main risk factors of QTc prolongation, which require enhanced attention. The present study showed that the Tisadale score had a stronger correlation and predictive accuracy for QTc prolongation than the Mayo Pro-QT score. As a result, the Tisadale risk score is a crucial assessment tool for psychotropic drug-intoxicated patients in a clinical setting.
Keywords
Psychotropic drugs; QTc prolongation; Torsades de pointes; Mayo Pro-QT score;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Brown TL, Gutierrez PM, Grunwald GK, et al. Access to Psychotropic Medication via Prescription Is Associated With Choice of Psychotropic Medication as Suicide Method: A Retrospective Study of 27,876 Suicide Attempts. J Clin Psychiatry. 2018;79(6):17m11982. Published 2018 Nov 6. doi:10.4088/JCP.17m11982.   DOI
2 Rautaharju PM, Surawicz B, Gettes LS, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part IV: the ST segment, T and U waves, and the QT interval: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology. Circulation. 2009;119(10):e241-e250. doi: 10.1161/CIRCULATIONAHA.108.191096   DOI
3 Haddad PM, Anderson IM. Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs 2002; 62(11):1649-71. doi:10.2165/00003495-200262110-00006   DOI
4 Chan A, Isbister GK, Kirkpatrick CM, et al. Drug-induced QT prolongation and torsades de pointes: evaluation of a QT nomogram. QJM 2007;100(10):609-15. doi:10.1093/qjmed/hcm072   DOI
5 Available at: https://www.oecd.org/. Accessed August 25, 2020 - Organisation for Economic Co-operation and Development
6 Available at: http://www.mohw.go.kr/. Accessed July 4, 2020 - 2018 National Survey on Suicide South Korea Ministry of Health and Welfare
7 Yap YG, Camm AJ. Drug induced QT prolongation and torsades de pointes. Heart 2003;89(11):1363-72. doi:10.1136/heart.89.11.1363   DOI
8 Schwartz PJ, Woosley RL. Predicting the Unpredictable: Drug-Induced QT Prolongation and Torsades de Pointes.?J Am Coll Cardiol 2016;67(13):1639-50. doi:10.1016/j.jacc.2015.12.063   DOI
9 Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004;350(10):1013-22. doi:10.1056/NEJMra032426   DOI
10 Drew BJ, Ackerman MJ, Funk M, 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 [published correction appears in Circulation. 2010 Aug 24;122(8):e440]. Circulation 2010;121(8):1047-60. doi: 10.1161/CIRCULATIONAHA.109.192704   DOI
11 Available at: https://www.crediblemeds.org/. Accessed July 15, 2020 - Woosley RL, Heise CW , Gallo T et al. QTdrugs List, [Accession Date], AZCERT, Inc. 1822 Innovation Park Dr., Oro Valley, AZ 85755
12 Available at: http://www.health.kr/. Accessed July 15, 2020 - Korea Pharmaceutical Information Center
13 Haugaa KH, Bos JM, Tarrell RF, et al. Institution-wide QT alert system identifies patients with a high risk of mortality. Mayo Clin Proc 2013;88(4):315-25. doi:10.1016/j.mayocp.2013.01.013   DOI
14 Baumert M, Porta A, Vos MA, et al. QT interval variability in body surface ECG: measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESC Working Group on Cardiac Cellular Electrophysiology. Europace 2016;18(6):925-44. doi:10.1093/europace/euv405   DOI
15 Wei K, Dorian P, Newman D, et al. Association between QT dispersion and autonomic dysfunction in patients with diabetes mellitus. J Am Coll Cardiol 1995;26(4):859-63. doi:10.1016/0735-1097(95)00279-8   DOI
16 Yang T, Snyders DJ, Roden DM. Rapid inactivation determines the rectification and [K+](o) dependence of the rapid component of the delayed rectifier K+ current in cardiac cells. Circ Res 1997;80(6):782-9. doi:10.1161/01.res.80.6.782   DOI
17 Numaguchi H, Johnson JP Jr, Petersen CI, Balser JR. A sensitive mechanism for cation modulation of potassium current. Nat Neurosci 2000;3(5):429-30. doi:10.1038/74793   DOI
18 Sarganas G, Garbe E, Klimpel A, et al.. Epidemiology of symptomatic drug-induced long QT syndrome and Torsade de Pointes in Germany. Europace 2014;16(1):101-8. doi:10.1093/europace/eut214   DOI
19 Girardin FR, Gex-Fabry M, Berney P, et al. Drug-induced long QT in adult psychiatric inpatients: the 5-year cross-sectional ECG Screening Outcome in Psychiatry study. Am J Psychiatry 2013;170(12):1468-76. doi:10.1176/appi.ajp.2013.12060860   DOI
20 Shao W, Ayub S, Drutel R, et al. QTc Prolongation Associated With Psychiatric Medications: A Retrospective Cross-Sectional Study of Adult Inpatients. J Clin Psychopharmacol 2019;39 (1):72-7. doi:10.1097/JCP.0000000000000992   DOI
21 Belardinelli L, Antzelevitch C, Vos MA. Assessing predictors of drug-induced torsade de pointes. Trends Pharmacol Sci 2003;24(12):619-25. doi:10.1016/j.tips.2003.10.002   DOI
22 Beach SR, Celano CM, Sugrue AM, et al. QT Prolongation, Torsades de Pointes, and Psychotropic Medications: A 5-Year Update. Psychosomatics 2018;59(2):105-22. doi:10.1016/j.psym.2017.10.009   DOI
23 Isbister GK, Friberg LE, Stokes B, et al. Activated charcoal decreases the risk of QT prolongation after citalopram overdose. Ann Emerg Med 2007;50(5):593-600.e6046. doi:10.1016/j.annemergmed.2007.03.009   DOI
24 Tisdale JE, Jaynes HA, Kingery JR, et al. Development and validation of a risk score to predict QT interval prolongation in hospitalized patients [published correction appears in Circ Cardiovasc Qual Outcomes. 2013 Nov;6(6):e57]. Circ Cardiovasc Qual Outcomes 2013;6(4):479-87. doi:10.1161/CIRCOUT-COMES.113.000152   DOI
25 Li M, Ramos LG. Drug-Induced QT Prolongation And Torsades de Pointes. PT 2017;42(7):473-7.
26 Castro VM, Clements CC, Murphy SN, et al. QT interval and anti-depressant use: a cross sectional study of electronic health records. BMJ 2013;346:f288. Published 2013 Jan 29. doi:10.1136/bmj.f288   DOI
27 Redfern WS, Carlsson L, Davis AS, et al. Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res 2003;58(1):32-45. doi:10.1016/s0008-6363(02)00846-5   DOI
28 Woosley RL, Romero K. Assessing cardiovascular drug safety for clinical decision-making. Nat Rev Cardiol 2013;10(6):330-7. doi:10.1038/nrcardio.2013.57   DOI
29 Reilly JG, Ayis SA, Ferrier IN, et al. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet 2000;355(9209):1048-52. doi:10.1016/s0140-6736(00)02035-3   DOI
30 van Noord C, Straus SM, Sturkenboom MC, et al. Psychotropic drugs associated with corrected QT interval prolongation. J Clin Psychopharmacol 2009;29(1):9-15. doi:10.1097/JCP.0b013e318191c6a8   DOI
31 Jasiak NM, Bostwick JR. Risk of QT/QTc prolongation among newer non-SSRI antidepressants. Ann Pharmacother 2014;48(12):1620-8. doi:10.1177/1060028014550645   DOI
32 Pohl R, K Yeragani V. QT interval variability in panic disorder patients after isoproterenol infusions. Int J Neuropsychopharmacol 2001;4(1):17-20. doi:10.1017/S146114570100219X   DOI
33 Ozeki Y, Fujii K, Kurimoto N, et al. QTc prolongation and antipsychotic medications in a sample of 1017 patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2010;34(2):401-5. doi:10.1016/j.pnpbp.2010.01.008   DOI
34 Harrigan EP, Miceli JJ, Anziano R, et al. A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. J Clin Psychopharmacol 2004;24(1):62-9. doi:10.1097/01.jcp.0000104913.75206.62   DOI
35 Sala M, Vicentini A, Brambilla P, et al. QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy. Ann Gen Psychiatry 2005;4(1):1. Published 2005 Jan 25. doi:10.1186/1744-859X-4-1   DOI
36 Kelmanson IA. High anxiety in clinically healthy patients and increased QT dispersion: a meta-analysis. Eur J Prev Cardiol 2014;21(12):1568-74. doi:10.1177/2047487313501613   DOI
37 Monitillo F, Leone M, Rizzo C, Passantino A, et al. Ventricular repolarization measures for arrhythmic risk stratification. World J Cardiol 2016;8(1):57-73. doi:10.4330/wjc.v8.i1.57   DOI