QT prolongation syndrome with Antipsychotic and Antidepressant Drugs
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Abstract
QT prolongation syndrome is a dangerous complication of psychopharmacotherapy and can cause the development of cardiac arrhythmia, leading to sudden death. The presented systematic literature review was performed based on a PubMed search for the keywords: drug-induced QT prolongation syndrome, cardiovascular side effects, cardiac arrhythmia, sudden death and antipsychotics or antidepressants. First-generation antipsychotics and especially thioridazine cause prolongation of the QT interval to the greatest extent. Of the second-generation antipsychotics, sertindole and ziprasidone have the greatest effect. Among antidepressants, the tricyclic antidepressants, citalopram and escitalopram, cause the most prolongation of the QT interval. Risk factors for the development of long QT syndrome in the use of antipsychotics and antidepressants have been identified. When prescribing psychotropic drugs that can cause a prolongation of the QT interval, it is necessary to follow certain principles of therapy, including dynamic monitoring of the ECG and electrolyte balance. In case of an increase in the initial corrected QT interval of more than 30 ms or an absolute value exceeding 500 ms, a dose reduction or discontinuation of the drug should be considered.
Keywords
QT prolongation syndrome, antipsychotics and antidepressants, cardiac arrhythmia, sudden death
References
- Drici M.D., Barhanin J. Cardiac K+ channels and drug-acquired long QT syndrome // Therapie. -2000.-Vol.55(1).-P.185–93.
- Al-Khatib S.M., Lapointe N.A., Kramer J.M., et al. What clinicians should know about the QT interval // JAMA.- 2003.-Vol.289.-P.2120–7.doi: 10.1001/jama.289.16.2120.
- Ольбинская Л.И., Игнатенко С.Б. Синдром удлиненного интервала QT // Клиническая фармакология и терапия.- 1999.-№5.-С. 44-46.
- Бокерия О. Л., Санакоев М. К. Синдром удлиненного QT-интервала //Анналы аритмологии. – 2015. – Т. 12. – №. 2. - С. 114-127.
- Bazett H.C. An analysis of the time-relations of electrocardiograms. // Heart .-1920.-Vol.7.-P. 353–370.
- Rautaharju P.M., Surawicz B., Gettes L.S,. 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 Co. J Am Coll Cardiol.- 2009.-Vol.53.-P.982–91.doi: 10.1016/j.jacc.2008.12.014.
- Khatib R., Sabir F.N., Omari C. et al. Managing drug-induced QT prolongation in clinical practice //Postgrad Med J. -2021.-Vol.97(1149).-P. 452-458. doi: 10.1136/postgradmedj-2020-138661.
- Stramba-Badiale M., Crotti L., Goulene K., et al. Electrocardiographic and genetic screening for long QT syndrome: results from a prospective study on 44,596 neonates // Circulation. - 2007, -Vol.116 (Abstr Suppl). II.- 377p.
- Zang X., Li ., Zhao Y. et al. Systematic meta-analysis of the association between a common NOS1AP genetic polymorphism, the QTc interval, and sudden death // Int Heart J.- 2019.-Vol.60.-P.1083–90. Doi:10.1536/ihj.19-024.
- Baracaldo-Santamaría D., Llinás-Caballero K., Corso-Ramirez J.M. et al. Genetic and Molecular Aspects of Drug-Induced QT Interval Prolongation // Int J Mol Sci. – 2021.-Vol.28,22(15).-P.8090. doi: 10.3390/ijms22158090.
- Остроумова 0.Д. Голобородова И.В. Лекарственно-индуцированное удлинение интервала QT: Распространенность, факторы риска, лечение и профилактика // Consilium Medicum.- 2019.- Вып.25-№5.-С.62-67. DOI: 10.26442/20751753.2019.5.190415.
- Roden D.M. Predicting drug-induced QT prolongation and torsades de pointes // J Physiol.- 2016.-Vol.594.-P.2459–68. doi: 10.1113/JP270526. Epub 2016 Jan 18.
- Zeltser D., Justo D., Halkin A. et al. Torsade de pointes due to noncardiac drugs most patients have easily identifiable risk factors // Medicine (Baltimore).- 2003.-Vol.82.-Vol.82.-P.282-90. doi: 10.1097/01.md.0000085057.63483.9b.
- Nachimuthu S., Assar M.D. Schussler JM. Drug-induced QT interval prolongation: mechanisms and clinical management // Ther Adv Drug Saf. -2012.-Vol.3(5).-P.241-53. doi: 10.1177/2042098612454283.
- Федеральное руководство по использованию лекарственных средств (формулярная система) / под ред. А.Г. Чучалина, В.В. Яснецова; Выпуск XIII. - Москва, 2012.
- Isbister G. K., Page C. B. Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice //British journal of clinical pharmacology. – 2013. – Т. 76. – №. 1. – С. 48-57. doi: 10.1111/bcp.12040.
- Sicouri S., Antzelevitch C. Sudden cardiac death secondary to antidepressant and antipsychotic drugs // Expert Opin Drug Saf.- 2008.-Vol.7(2).-P.181–194.doi: 10.1517/14740338.7.2.181.
- Gury C., Canceil O., Iaria P. Antipsychotic drugs and cardiovascular safety: current studies of prolonged QT interval and risk of ventricular arrhythmia // Encephale.- 2000.-Vol.26.-P.62-72.
- Taipale H., Mittendorfer-Rutz E., Alexanderson K. et al. Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia // Schizophr Res. -2018.-Vol.197.-P.274-280. doi: 10.1016/j.schres.2017.12.010.
- Herxheimer A., Healy D. Arrythmias and sudden death in patients taking antipsychotic drugs.// BMI.- 2002.-Vol. 30;325(7375).-P.1253-4. doi: 10.1136/bmj.325.7375.1253.
- Glassman A., Bigger J. Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death // Am. J. Psychiat .- 2001.- Vol. 158.- P. 1774–1782. doi: 10.1176/appi.ajp.158.11.1774.
- Witchel H., Hancox J. and Nutt D. Psychotropic drugs, cardiac arrhythmia, and sudden death //J Clin Psychopharmacol.-2003.-Vol. 23.-P. 58-77. doi: 10.1097/00004714-200302000-00010.
- Zhu J., Hou W., Xu Y. et al. Antipsychotic drugs and sudden cardiac death: A literature review of the challenges in the prediction, management, and future steps // Psychiatry Res.- 2019.-Vol.281.-P.:112598. doi: 10.1016/j.psychres.2019.112598.
- Pickham D., Helfenbein E., Shinn J. A. et al. High prevalence of corrected QT interval prolongation in acutely ill patients is associated with mortality: Results of the QT in Practice (QTIP) Study// Critical Care Medicine.- 2012.-Vol 2(40).-P.394-9. doi: 10.1097/CCM.0b013e318232db4a.
- Ozeki Y., Fujii K., Kurimoto N. et al. QTc prolongation and antipsychotic medications in a sample of 1017 patients with schizophreni // Prog Neuropsychopharmacol Biol Psychiatry. 2010 Mar 17;34(2):401-5. doi: 10.1016/j.pnpbp.2010.01.008.
- Zareba W., Lin D.A. Antipsychotic drugs and QT interval prolongation //Psychiatr Q.- 2003.-Vol.74(3).-P.291-306. doi: 10.1023/a:1024122706337.
- Muir W.W., Strauch S.M., Schaal S.F. Effects of tricyclic antidepressant drugs on the electrophysiological properties of dog Purkinje fibers // J Cardiovasc Pharmacol.- 1982.-Vol.-P.82–90. doi: 10.1097/00005344-198201000-00014.
- Valenzuela C., Sánchez-Chapula J., Delpón E. et al. Imipramine blocks rapidly activating and delays slowly activating K+ current activation in guinea pig ventricular myocytes //Circ Res. -1994.-Vol.74(4).-P.687-99. doi: 10.1161/01.res.74.4.
- Aunsholt N.A. Prolonged Q-T interval and Hypokalemia by haloperidol // Acta Psychiatr Scand. -1989. -Vol.79(4).- P. 411-420. doi: 10.1111/j.1600-0447.1989.tb10279.x.
- Pacher P., Kecskemet V. Cardiovascular Side Effects of New Antidepressants and Antipsychotics: New Drugs, old Concerns? // Curr Pharm Des.- 2004.-Vol.10(20).-P. 2463–2475. doi: 0.2174/1381612043383872.
- Buckley N.A., Whyte I.M., Dawson A.H. Cardiotoxicity more common in thioridazine overdose than with other neuroleptics //J Toxicol Clin Toxicol.- 1995.-Vol.33.-P.199-204. doi:10.3109/15563659509017984.
- Gottschalk E., Dinovo E., Biener R., Nandi. B. Plasma concentrations of thioridazine metabolites and ECG abnormalities // Jю Pharm. Sci. - 1978. - Vol. 67(2). P. 155–157. doi: 10.1002/jps.2600670208.
- Мосолов С.Н., Цукарзи Э.Э., Алфимов П.В. Алгоритмы биологической терапии шизофрении. // Современная терапия психических расстройств. 2014. № 1. С. 27-36.
- Novartis Gives Mellaril Black Box Warning to Alert MDs of Arrhythmia Risk. Reuters Health Jul 26, 2000. ttp://www.reutershealth.com/frame2/arch.html. 150.
- Федеральное руководство по использованию лекарственных средств (формулярная система) / под ред. А. Г. Чучалина, Ю. Б. Белоусова, В. В. Яснецова. Москва, 2009. (10-е издание, переработанное и дополненное).
- Metzger E., Friedman R. Prolongation of the corrected QT and torsades de pointes cardiac arrhythmia associated with intravenous haloperidol in the medically ill // J Clin Psychopharmacol.- 1993.- Vol. 13 (2).- P. 128–32.
- Мосолов С.Н., Цукарзи Э.Э. Психофармакотерапия шизофрении. // В книге: Психиатрия: национальное руководство / ред. Незнанов Н.Г., Александровский Ю.А./ Москва, 2018. С. 299-328.
- Gury C., Canceil O., Iaria P. Antipsychotic drugs and cardiovascular safety: current studies of prolonged QT interval and risk of ventricular arrhythmia // Encephale.- 2000.-Vol.26.-P.62-72.
- Bordet C., Garcia P., Salvo F. et al. Antipsychotics and risk of QT prolongation: a pharmacovigilance study// Psychopharmacology (Berl).- 2023.-Vol.240(1).-P.199-202. doi: 10.1007/s00213-022-06293-4. Epub 2022 Dec 14.
- Leonard C.E., Freeman C.P., Newcomb C.W. 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 Cardiolog.- 2013.-Vol. Suppl 10(6).-P.1-9. doi: 10.4172/2155-9880.S10-006.
- Welch R, Chue P. Antipsychotic agents and QT changes // J Psychiatry Neurosci. -2000.- Vol. 25(2).-P.154-60.
- Nielsen J., Wang F., Graff C., Kanters J. QT dynamics during treatment with sertindole // Ther Adv Psychopharmacol. -2015- Vol5(1) - P.26-31.. doi: 10.1177/2045125314560738. PMID: 25653828.
- Lewis R., Bagnall A., Leitner M. Sertindole for schizophrenia. Cochrane Database Syst Rev. -2000..-Vol;(2).-CD001715. doi: 10.1002/14651858.CD001715. Update in: Cochrane Database Syst Rev. 2005;(3):CD001715.
- Beach S.R., Celano C.M., Noseworthy P.A. et al. QTc prolongation, torsades de pointes, and psychotropic medications // Psychosomatics.- 2013.-Vol.;54(1).-P.1-13. doi: 10.1016/j.psym.2012.11.001.
- Beach S.R., Celano C.M., Sugrue A.M. et al. QT Prolongation, Torsades de Pointes, and Psychotropic Medications: A 5-Year Update //Psychosomatics. -2018.Vol.59(2).-P.105-122. doi: 10.1016/j.psym.2017.10.009. Epub 2017 Nov 3.
- Barabássy Á., Sebe B., Acsai K, Laszlovszky I. et al. Safety and Tolerability of Cariprazine in Patients with Schizophrenia: A Pooled Analysis of Eight Phase II/III Studies // Neuropsychiatr Dis Treat. -2021.-Vol. 7;17.-P.957-970. doi: 10.2147/NDT.S301225. Erratum in: Neuropsychiatr Dis Treat. 2021 May 17;17:1481.
- Sanford M. Lurasidone: in the treatment of schizophrenia // CNS Drugs. -2013. Vol.27(1).-P.67-80. doi: 10.1007/s40263-012-0026-x.
- Spina E., Hiemke C., de Leon J. Assessing drug-drug interactions through therapeutic drug monitoring when administering oral second-generation antipsychotics // Expert Opin Drug Metab Toxicol.- 2016.-Vol.12(4).-P.407-22. doi: 10.1517/17425255.2016.1154043. Epub 2016 Feb 29.
- Костюк Г.П., Шмуклер А.Б., Голубев С.А. и др. Эпидемиологические аспекты диагностики шизофрении в Москве // Социальная и клиническая психиатрия. – 2017. – No 3. – С. 5–9.
- Westaway K., Sluggett J., Alderman C. et al. Prevalence of multiple antipsychotic use and associated adverse effects in Australians with mental illness // Int J Evid-Based Healthc. – 2016. – Vol. 14 (3). – Pp. 104–112. doi:10.1097/XEB.0000000000000082.
- Takeuchi H., Suzuki T., Remington G., Uchida H. Antipsychotic Polypharmacy and Corrected QT Interval: A Systematic Review // Can J Psychiatry.-2015.-Vol.60(5).-P.215-22. doi: 10.1177/070674371506000503. Erratum in: Can J Psychiatry. 2015 Oct;60(10):426.
- Kim K., Kim Y.S., Joo E.J.et al. Clozapine Blood Concentration Predicts Corrected QT-Interval Prolongation in Patients With Psychoses // J Clin Psychopharmacol. – 2022. Vol.42(6):536-543. doi: 10.1097/JCP.0000000000001605.
- Yap Y.G, Camm J. Risk of torsades de pointes with non-cardiac drugs. Doctors need to be aware that many drugs can cause qt prolongation // BMJ. – 2000.-Vol.29;320(7243).-P.1158-9. doi: 10.1136/bmj.320.7243.1158.
- Мосолов С.Н. Клиническое применение современных антидепрессантов. С-П., «Медицинское информационное агентство", 1995, 568с.
- Aronow W.S., Shamliyan T.A. Effects of antidepressants on QT interval in people with mental disorders // Arch Med Sci. – 2020.-Vol. 29;16(4).-P.727-741. doi: 10.5114/aoms.2019.86928.
- Burckhardt D., Raeder E., Muller V. et al. Cardiovascular effects of tricyclic and tetracyclic antidepressants // JAMA.-1978.-Vol. 16;239(3).-P.:213–6.
- Glassman A.H., Bigger J.T. Jr Cardiovascular effects of therapeutic doses of tricyclic antidepressants. A review // Arch Gen Psychiatry. -1981.-Vol.38.-P.815–20. doi: 10.1001/archpsyc.1981.01780320095011.
- Baker B., Dorian P., Sandor P. et al. Electrocardiographic effects of fluoxetine and doxepin in patients with major depressive disorder // J Clin Psychopharmacol. -1997.-Vol.17(1).-P.15-21. doi: 10.1097/00004714-199702000-00004.
- Feenstra J., Grobbee D.E., Remme W.J. et al. Drug-induced heart failure // Journal of the American College of Cardiology. – 1999. – Vol. 33. – P. 1152—1162. Doi:10.1016/s0735-1097(99)00006-6. 51.
- Aronow W.S., Shamliyan T.A. Effects of antidepressants on QT interval in people with mental disorders // Arch Med Sci. -2020.-Vol. 29;16(4).-P.727-741. doi: 10.5114/aoms.2019.86928.
- Funk K.A., Bostwick J.R. A comparison of the risk of QT prolongation among SSRIs //Ann Pharmacother.-2013.-Vol.47(10).-P.1330-41. doi: 10.1177/1060028013501994. Epub 2013 Oct 21.
- Bose A., Li D., Gandhi C. Escitalopram in the acute treatment of depressed patients aged 60 years or older // Am J Geriatr Psychiatry.- 2008.-Vol.16.-P. 14-20 doi: 10.1097/JGP.0b013e3181591c09.
- Thase M.E., Larsen K.G., Reines E., Kennedy S.H. The cardiovascular safety profile of escitalopram // Eur Neuropsychopharmacol.-2013.-Vol.23.-P. 1391-400. doi: 10.1016/j.euroneuro.2013.05.011. Epub 2013 Aug 6.
- Tampi R.R, Balderas M., Carter K.V, et al. Citalopram, QTc prolongation, and torsades de pointes // Psychosomatics.- 2015.-Vol. 56.-P. 36-43. doi: 10.1016/j.psym.2014.09.002. Epub 2014 Sep 6.
- U.S. Food and Drug Administration. FDA Drug Safety Communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses. Drug Safety and Availability 2012; https://www.fda.gov/Drugs/DrugSafety/ucm297391.htm.
- Whyte I.M., Dawson A.H., Buckley N.A. Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants // QJM. – 2003.- Vol.;96(5).-P.369-74. doi: 10.1093/qjmed/hcg062.
- Kok R., Nolen W., Heeren T. Cardiovascular changes associated with venlafaxine in the treatment of late-life depression // Am J Geriatr Psychiatr.- 2007.- Vol. 15.-P. 725. doi: 10.1097/JGP.0b013e3180488358.
- Bavle A. Venlafaxine induced QTc interval prolongation in a therapeutic dose // Asian J Psychiatr.- 2015.- Vol.16.-P. 63-4. doi: 10.1016/j.ajp.2015.06.001. Epub 2015 Jun 28
- Letsas K., Korantzopoulos P., Pappas L. et al. QT interval prolongation associated with venlafaxine administration // Int J Cardiol.- 2006.-Vol.109.-P. 116-7. doi: 10.1016/j.ijcard.2005.03.065.
- Bordet C., Rousseau V., Montastruc F., Montastruc J.L. QT prolongation and vortioxetine: A postmarketing study and comparison with other serotonin reuptake inhibitors. Psychopharmacology (Berl.). 2020; 237(4): 1245–1247. Doi: 10.1007/s00213-020-05461-8.