cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLC10.15829/1728-8800-2012-5-79-82cardiovascular-1924Research ArticleОБЗОРЫREVIEWSВнезапная сердечная смерть и антипсихотические препараты (обзор иностранной литературы)Sudden cardiac death and antipsychotic medications: literature reviewВолковВ. П.VolkovV. P.patowolf@yandex.ruОбластная клиническая психиатрическая больница № 1 им. М. П. Литвинова, ТверьM. P. Litvinov Regional Clinical Psychiatric Hospital No. 1, Tver2012201020121157982Copyright © Волков В.П., 20122012Волков В.П.Volkov V.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/1924

В статье обобщены результаты исследований, опубликованных в зарубежной литературе, касающиеся внезапной сердечной смерти (ВСС), наступившей у психически больных при нейролептической терапии. Даны современные определения ВСС, приведены эпидемиологические данные, освещены вопросы патогенеза смертельных аритмий, обусловленных побочным кардиотоксическим эффектом антипсихотиков. Значительное внимание уделено изменениям электрокардиограммы, в частности, интервала QT, вызванным нейролептическими препаратами, а также факторам риска развития ВСС и принципам ее профилактики.

The review summarises the evidence from international publications on sudden cardiac death (SCD) in psychiatric patients receiving neuroleptics. Modern SCD definitions are presented, together with the relevant epidemiological data. The pathogenesis of fatal cardiac arrhythmias, caused by cardiotoxic effects of antipsychotic medications, is discussed. Electrocardiographic changes, in particular QT interval changes, as well as risk factors of SCD and main principles of its prevention, are described in detail.

нейролептикикардиотоксичностьинтервал QTвнезапная сердечная смертьneurolepticscardiotoxicityQT intervalsudden cardiac deathReferencesAbdelmawla N, Mitchell AJ. Sudden cardiac death and antipsychotics. Part 1: Risk factors and mechanisms. Adv Psychiatr Treat 2006; 12: 35-44.Abdelmawla N, Mitchell AJ. Sudden cardiac death and antipsychotics. Part 1: Risk factors and mechanisms. Adv Psychiatr Treat 2006; 12: 35-44.Royal College of Psychiatrists. The Association between Anti-psychotic Drugs and Sudden Death. Council Report CR 57. London 1997.Royal College of Psychiatrists. The Association between Anti-psychotic Drugs and Sudden Death. Council Report CR 57. London 1997.Sovari AA, Kocheril AG, Baas AS. Sudden Cardiac Death. 2011. emedicine. medscape.com/article/151907-overview.Sovari AA, Kocheril AG, Baas AS. Sudden Cardiac Death. 2011. emedicine. medscape.com/article/151907-overview.Straus SMJM, Sturkenboom MCJM, Bleumink GS, et al. Non-cаrdiac QTc-prolonging drugs and the risk of sudden cardiac death. Eur Heart J 2005; 26: 2007-12.Straus SMJM, Sturkenboom MCJM, Bleumink GS, et al. Non-cаrdiac QTc-prolonging drugs and the risk of sudden cardiac death. Eur Heart J 2005; 26: 2007-12.Witchel HJ, Hancox JC, Nutt DJ. Psychotropic Drugs, Cardiac Frrhythmia, and Sudden Death. J Clin Psychopharmacol 2003; 23: 58-77.Witchel HJ, Hancox JC, Nutt DJ. Psychotropic Drugs, Cardiac Frrhythmia, and Sudden Death. J Clin Psychopharmacol 2003; 23: 58-77.Michaud K, Letsta MM, Fellmann F, Mangin P. Molecular autopsy of sudden cardiac death: from postmortem to clinical approach. Med Suisse 2008; 4(164): 1590-3.Michaud K, Letsta MM, Fellmann F, Mangin P. Molecular autopsy of sudden cardiac death: from postmortem to clinical approach. Med Suisse 2008; 4(164): 1590-3.Myerberg RJ. Cardiac arrest and sudden cardiac death. In: Braunwald E, ed. A Text Book of Cardiovascular Medicine. New York: WB Saunders 1997. 742-79.Myerberg RJ. Cardiac arrest and sudden cardiac death. In: Braunwald E, ed. A Text Book of Cardiovascular Medicine. New York: WB Saunders 1997. 742-79.Priori SG, Alliot E, Blomstrom-Lundqvit C, et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 2001; 22: 1374-450.Priori SG, Alliot E, Blomstrom-Lundqvit C, et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 2001; 22: 1374-450.Reilly JG, Ayis SA, Ferrier IN, et al. Thioridazine and sudden unexplained death in psychiatric in-patients. Br J Psychiatry 2002; 180: 515-22.Reilly JG, Ayis SA, Ferrier IN, et al. Thioridazine and sudden unexplained death in psychiatric in-patients. Br J Psychiatry 2002; 180: 515-22.Glassman AH, Bigger JT, Jr. Antipsychotic Drugs: Prolonged QTc Interval, Torsade de Pointes, and Sudden Death. Am J Psychiatry 2001; 158: 1774-82.Glassman AH, Bigger JT, Jr. Antipsychotic Drugs: Prolonged QTc Interval, Torsade de Pointes, and Sudden Death. Am J Psychiatry 2001; 158: 1774-82.Herxheimer A, Heali D. Arrhythmias and sudden death in patients taking antipsychotic drugs: High doses and combinations of certain drug are best avoided. BMJ 2002; 325: 1253-4.Herxheimer A, Heali D. Arrhythmias and sudden death in patients taking antipsychotic drugs: High doses and combinations of certain drug are best avoided. BMJ 2002; 325: 1253-4.Koponen H, Alaraisanen A, Saari K, et al. Schizophrenia and sudden cardiac death: a review. Nord J Psychiatry 2008; 62(5): 342-5.Koponen H, Alaraisanen A, Saari K, et al. Schizophrenia and sudden cardiac death: a review. Nord J Psychiatry 2008; 62(5): 342-5.Alvarez PA, Pahissa J. QT alterations in psychopharmacology: proven candidates and suspects. Curr Drug Saf 2010; 5(1): 97-104.Alvarez PA, Pahissa J. QT alterations in psychopharmacology: proven candidates and suspects. Curr Drug Saf 2010; 5(1): 97-104.Frassati D, Tabib A, Lachaux B, et al. Hidden Cardiac Lesions and Psychotropic Drugs as a Possible Cause of Sudden Death in Psychiatric Patients: A Report of 14 Cases and Review of the Literature. Can J Psychiatry 2004; 49: 100-5.Frassati D, Tabib A, Lachaux B, et al. Hidden Cardiac Lesions and Psychotropic Drugs as a Possible Cause of Sudden Death in Psychiatric Patients: A Report of 14 Cases and Review of the Literature. Can J Psychiatry 2004; 49: 100-5.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: 1070.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: 1070.Jolly K, Gammage MD, Cheng KK, et al. Sudden death in patients receiving drugs tending to prolong the QT interval. Br J Clin Pharmacol 2009; 68(5): 743-51.Jolly K, Gammage MD, Cheng KK, et al. Sudden death in patients receiving drugs tending to prolong the QT interval. Br J Clin Pharmacol 2009; 68(5): 743-51.Mackin P. Cardiac side effects of psychiatric drugs. Hum Psychopharmacol 2008; 23(Suppl 1): 3-14.Mackin P. Cardiac side effects of psychiatric drugs. Hum Psychopharmacol 2008; 23(Suppl 1): 3-14.Narang P, El-Rafai M, Parlapalli R, et al. Antipsychotic drugs: sudden cardiac death among elderly patients. Psychiatry (Edmont) 2010; 7(10): 25-9.Narang P, El-Rafai M, Parlapalli R, et al. Antipsychotic drugs: sudden cardiac death among elderly patients. Psychiatry (Edmont) 2010; 7(10): 25-9.Haddad PM, Anderson IM. Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs 2002; 62: 1649-71.Haddad PM, Anderson IM. Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs 2002; 62: 1649-71.Olsen KM. Pharmacologic agents associated with QT interval prolongation. J Fam Pract 2005; Suppl: 8-14.Olsen KM. Pharmacologic agents associated with QT interval prolongation. J Fam Pract 2005; Suppl: 8-14.Straus SMJM, Bleumink GS, Dieleman JP, et al. Antipsychotics and the risk of sudden cardiac death. Arch Int Med 2004; 164: 1293-7.Straus SMJM, Bleumink GS, Dieleman JP, et al. Antipsychotics and the risk of sudden cardiac death. Arch Int Med 2004; 164: 1293-7.Coffey S, McNicholl IR. Antipsychotics and Sudden Cardiac Death. HIV Med Q Res Brief 2009.Coffey S, McNicholl IR. Antipsychotics and Sudden Cardiac Death. HIV Med Q Res Brief 2009.Ray WA, Chung CP, Murray KT, et al. Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death. N Engl J Med 2009; 360: 225-35.Ray WA, Chung CP, Murray KT, et al. Atypical Antipsychotic Drugs and the Risk of Sudden Cardiac Death. N Engl J Med 2009; 360: 225-35.Royal College of Psychiatrists. Consensus statement on high-dose antipsychotic medication. Council Report CR 138. London 2006.Royal College of Psychiatrists. Consensus statement on high-dose antipsychotic medication. Council Report CR 138. London 2006.Van Noord C, Sturkenboom MC, Straus SV, et al. Non-cardiovascular drugs that inhibit HERG-encoded potassium channels and risk of sudden cardiac death. Heart 2011; 97(3): 215-20.Van Noord C, Sturkenboom MC, Straus SV, et al. Non-cardiovascular drugs that inhibit HERG-encoded potassium channels and risk of sudden cardiac death. Heart 2011; 97(3): 215-20.Lieberman JA, Merrill D, Parameswaran S. APA Guidance on the Use of Antipsychotic Drugs and Cardiac Sudden Death. http://www.omh.state.ny.us/omhweb/advisories/adult_antipsychotic_use_attachement.htmlLieberman JA, Merrill D, Parameswaran S. APA Guidance on the Use of Antipsychotic Drugs and Cardiac Sudden Death. http://www.omh.state.ny.us/omhweb/advisories/adult_antipsychotic_use_attachement.htmlGlassman AH. Schizophrenia, antipsychotic drugs, and cardiovascular disease. J Clin Psychiatry 2005; 66 Suppl 6: 5-10.Glassman AH. Schizophrenia, antipsychotic drugs, and cardiovascular disease. J Clin Psychiatry 2005; 66 Suppl 6: 5-10.Abdelmawla N, Mitchell AJ. Sudden cardiac death and antipsychotic drugs. Part 2: Monitoring and prevention. Adv Psychiatr Treat 2006; 12: 100-9.Abdelmawla N, Mitchell AJ. Sudden cardiac death and antipsychotic drugs. Part 2: Monitoring and prevention. Adv Psychiatr Treat 2006; 12: 100-9.Engdahl J, Holmberg M, Karlson BW, et al. The epidemiology of out-ofhospital “sudden” cardiac arrest. Resuscitation 2002; 52: 235-45.Engdahl J, Holmberg M, Karlson BW, et al. The epidemiology of out-ofhospital “sudden” cardiac arrest. Resuscitation 2002; 52: 235-45.Killeen MJ. Antipsychotic-induced sudden cardiac death: examination of an atypical reaction. Expert Opin Drug Saf 2009; 8(3): 249-52.Killeen MJ. Antipsychotic-induced sudden cardiac death: examination of an atypical reaction. Expert Opin Drug Saf 2009; 8(3): 249-52.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: 32-45.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: 32-45.Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004; 350: 1013-22.Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004; 350: 1013-22.Podrid PhJ, Kowey PR. Handbook of cardiac arrhythmia. Baltimore: Williams a. Wilkins 1996; 459.Podrid PhJ, Kowey PR. Handbook of cardiac arrhythmia. Baltimore: Williams a. Wilkins 1996; 459.Meyer FP, Geller JC. QT-Interval-Verlangerung durch Pharmaka Kardiotoxizitat von Arzneimitteln. Monatsschr Kinderheilkd 2004 – http:// medafarm.ru.Meyer FP, Geller JC. QT-Interval-Verlangerung durch Pharmaka Kardiotoxizitat von Arzneimitteln. Monatsschr Kinderheilkd 2004 – http:// medafarm.ru.Montanez A, Ruskin JN, Hebert PR, et al. Prolonged QTc interval and risks of total and cardiovascular mortality and sudden death in the general population. A review and qualitative overview of the prospective cohort studies. Arch Int Med 2004; 164: 943-8.Montanez A, Ruskin JN, Hebert PR, et al. Prolonged QTc interval and risks of total and cardiovascular mortality and sudden death in the general population. A review and qualitative overview of the prospective cohort studies. Arch Int Med 2004; 164: 943-8.Taylor DM. Antipsychotics and QT prolongation. Acta Psychiatr Scand 2003; 107: 85-95.Taylor DM. Antipsychotics and QT prolongation. Acta Psychiatr Scand 2003; 107: 85-95.Frimas V, Roberge C, Perroux D, Dauvillier JM. Cardiological monitoring of antipsychotic-treated patients: evaluation and evolution of a hospital protocol. Encephale 2008; 34(5): 467-76.Frimas V, Roberge C, Perroux D, Dauvillier JM. Cardiological monitoring of antipsychotic-treated patients: evaluation and evolution of a hospital protocol. Encephale 2008; 34(5): 467-76.Justo D, Prokhorov V, Heller K, Zeltser D. Torsade de points induced by psychotropic drugs and the prevalence of its risk factors. Acta Psychiatr Scand 2005; 111(3): 171-6.Justo D, Prokhorov V, Heller K, Zeltser D. Torsade de points induced by psychotropic drugs and the prevalence of its risk factors. Acta Psychiatr Scand 2005; 111(3): 171-6.Vieweg WV, Wood MA, Fernandez A, et al. Proarrhythmic risk with antipsychotic and antidepressant drugs: implication in the elderly. Drugs Aging 2009; 26(12): 997-1012.Vieweg WV, Wood MA, Fernandez A, et al. Proarrhythmic risk with antipsychotic and antidepressant drugs: implication in the elderly. Drugs Aging 2009; 26(12): 997-1012.Zareba W, Lin DA. Antipsychotic drugs and QT interval prolongation. Psychiatr Q. 2003; 74(3): 291-306.Zareba W, Lin DA. Antipsychotic drugs and QT interval prolongation. Psychiatr Q. 2003; 74(3): 291-306.Van de Kraats GB, Slob J, Tenback DE. Reduction of prolonged QTcinterval related risks with neuropharmacological drugs. Recommendations for clinical practice. Tijdschr Psychiatr 2007; 49(1): 43-7.Van de Kraats GB, Slob J, Tenback DE. Reduction of prolonged QTcinterval related risks with neuropharmacological drugs. Recommendations for clinical practice. Tijdschr Psychiatr 2007; 49(1): 43-7.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: 62-9.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: 62-9.Reilly JG, Ayis SA, Ferrier IN, et al. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet 2000; 355: 1048-52.Reilly JG, Ayis SA, Ferrier IN, et al. QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet 2000; 355: 1048-52.Mackin P, Young AH. QTc interval measurement and metabolic parameters in psychiatric patients taking typical or atypical antipsychotic drugs: a preliminary study. J Clin Psychiatry 2005; 66(11): 1386-91.Mackin P, Young AH. QTc interval measurement and metabolic parameters in psychiatric patients taking typical or atypical antipsychotic drugs: a preliminary study. J Clin Psychiatry 2005; 66(11): 1386-91.Bouman WH, Pinner G. Use of atypical antipsychotic drugs in old age psychiatry. Adv Psychiatr Treat 2002; 8: 49-58.Bouman WH, Pinner G. Use of atypical antipsychotic drugs in old age psychiatry. Adv Psychiatr Treat 2002; 8: 49-58.Rautaharju PM, Zhang ZM. Linearly scaled, rate-invariant normal limits for QT interval: eight decades of incorrect application of power functions. J Cardiovasc Electrophysiol 2002; 12: 1211-8.Rautaharju PM, Zhang ZM. Linearly scaled, rate-invariant normal limits for QT interval: eight decades of incorrect application of power functions. J Cardiovasc Electrophysiol 2002; 12: 1211-8.Tie H, Walker BD, Valenzuela SM, et al. The heart of psychotropic drug therapy. Lancet 2000; 355: 1825.Tie H, Walker BD, Valenzuela SM, et al. The heart of psychotropic drug therapy. Lancet 2000; 355: 1825.Makita N, Horie M, Nakamura T, et al. Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation. Circulation 2002; 106: 1269-74.Makita N, Horie M, Nakamura T, et al. Drug-induced long-QT syndrome associated with a subclinical SCN5A mutation. Circulation 2002; 106: 1269-74.Kutscher EC, Carnahan R. Common CYP450 interactions with psychiatric medicines: A brief review for the primary care physician. S D Med 2006; 59(1): 5-9.Kutscher EC, Carnahan R. Common CYP450 interactions with psychiatric medicines: A brief review for the primary care physician. S D Med 2006; 59(1): 5-9.Sanguinetti MC, Jiang C, Curran ME, Keating MT. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the Ikr potassium channel. Cell 1995; 81: 299-307.Sanguinetti MC, Jiang C, Curran ME, Keating MT. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the Ikr potassium channel. Cell 1995; 81: 299-307.Crumb WJ, Beasley C, Thornton A, et al. Cardiac ion channel blocking profile of olanzapine and other antipsychotics. Presented at the 38th American College of Neuropsychopharmacology Annual Meeting. Acapulco, Mexico 1999.Crumb WJ, Beasley C, Thornton A, et al. Cardiac ion channel blocking profile of olanzapine and other antipsychotics. Presented at the 38th American College of Neuropsychopharmacology Annual Meeting. Acapulco, Mexico 1999.Brett AS. Neuroleptics and Sudden Cardiac Death. J Watch Gen Med 2009. general-medicine.jwatch.org>cgi/content/full/2009Brett AS. Neuroleptics and Sudden Cardiac Death. J Watch Gen Med 2009. general-medicine.jwatch.org>cgi/content/full/2009Marder SR, Essock SM, Miller AL, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry 2004; 161: 1334-49.Marder SR, Essock SM, Miller AL, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry 2004; 161: 1334-49.Taylor D, Paton C, Kerwin R, eds. The Maudsley 2005–2006 Prescribing Guidelines (8th edn). London: Taylor a. Francis 2005.Taylor D, Paton C, Kerwin R, eds. The Maudsley 2005–2006 Prescribing Guidelines (8th edn). London: Taylor a. Francis 2005.Schneeweiss S, Avorn J. Antipsychotic agents and sudden cardiac death – how should we manage the risk? N Engl J Med 2009; 360(3): 294-6.Schneeweiss S, Avorn J. Antipsychotic agents and sudden cardiac death – how should we manage the risk? N Engl J Med 2009; 360(3): 294-6.

The authors declare that there are no conflicts of interest present.