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Review

Cardiovascular safety of antipsychotics: a clinical overview

ORCID Icon, , , &
Pages 679-688 | Received 17 Jan 2016, Accepted 24 Feb 2016, Published online: 01 Apr 2016

References

  • Correll CU, Nielsen J. Antipsychotic-associated all-cause and cardiac mortality: what should we worry about and how should the risk be assessed? Acta Psychiatr Scand. 2010;122:341–344.
  • Ray WA, Chung CP, Murray KT, et al. Atypical antipsychotic drugs and the risk of sudden cardiac death. N Engl J Med. 2009;360:225–235.
  • Nielsen J, Munk-Jørgensen P, Skadhede S, et al. Determinants of poor dental care in patients with schizophrenia: a historical, prospective database study. J Clin Psychiatry. 2011;72:140–143.
  • Marder SR, Essock SM, Miller AL, et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry. 2004;161:1334–1349.
  • Henderson DC, Vincenzi B, Andrea NV, et al. Pathophysiological mechanisms of increased cardiometabolic risk in people with schizophrenia and other severe mental illnesses. Lancet Psychiatry. 2015;2:452–464.
  • Nielsen J. The safety of atypical antipsychotics: does QTc provide all the answers? Expert Opin Drug Saf. 2011;10:341–344.
  • Shah AA, Aftab A, Coverdale J. QTc prolongation with antipsychotics: is routine ECG monitoring recommended? J Psychiatr Pract. 2014;20:196–206.
  • Nielsen J, Graff C, Kanters JK, et al. Assessing QT interval prolongation and its associated risks with antipsychotics. CNS Drugs. 2011;25:473–490.
  • Raschi E, Poluzzi E, Godman B, et al. Torsadogenic risk of antipsychotics: combining adverse event reports with drug utilization data across Europe. PLoS One. 2013;8:e81208.
  • Poluzzi E, Raschi E, Koci A, et al. Antipsychotics and torsadogenic risk: signals emerging from the US FDA adverse event reporting system database. Drug Saf. 2013;36:467–479.
  • Raschi E, Poluzzi E, Salvo F, et al. The contribution of national spontaneous reporting systems to detect signals of torsadogenicity: issues emerging from the ARITMO project. Drug Saf. 2016;39:59–68.
  • Weeke P, Jensen A, Folke F, et al. Antipsychotics and associated risk of out-of-hospital cardiac arrest. Clin Pharmacol Ther. 2014;96:490–497.
  • Salvo F, Pariente A, Shakir S, et al. Sudden cardiac and sudden unexpected death related to antipsychotics: a meta-analysis of observational studies. Clin Pharmacol Ther. 2015. published online 14 August 2015. doi:10.1002/cpt.250.
  • Goldenberg I, Moss AJ, Zareba W. QT interval: how to measure it and what is “normal”. J Cardiovasc Electrophysiol. 2006;17:333–336.
  • FDA. Psychopharmacological drugs advisory committee: briefing document for Zeldox® capsules (ziprasidone HCl). 2000. [cited 2016 Feb 17]. Available from: http://www.fda.gov/ohrms/dockets/ac/00/backgrd/3619b1a.pdf
  • Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353:1209–1223.
  • 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;382:951–962.
  • Michelsen JW, Meyer JM. Cardiovascular effects of antipsychotics. Expert Rev Neurother. 2007;7:829–839.
  • Hassaballa HA, Balk RA. Torsade de pointes associated with the administration of intravenous haloperidol: a review of the literature and practical guidelines for use. Expert Opin Drug Saf. 2003;2:543–547.
  • Meyer-Massetti C, Cheng CM, Sharpe BA, et al. The FDA extended warning for intravenous haloperidol and torsades de pointes: how should institutions respond? J Hosp Med. 2010 Apr;5:E8E16.
  • FDA. Atypical antipsychotic drugs information. 2015. [cited 2016 Feb 17]. Available from: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm094303.htm
  • Citrome L. Drug safety evaluation of ziprasidone. Expert Opin Drug Saf. 2011;10:437–448.
  • Hasnain M, Vieweg WV. QTc interval prolongation and torsade de pointes associated with second-generation antipsychotics and antidepressants: a comprehensive review. CNS Drugs. 2014;28:887–920.
  • 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;24:62–69.
  • Pae C-U. Sertindole: dilemmas for its use in clinical practice. Expert Opin Drug Saf. 2013;12:321–326.
  • Karamatskos E, Lambert M, Mulert C, et al. Drug safety and efficacy evaluation of sertindole for schizophrenia. Expert Opin Drug Saf. 2012;11:1047–1062.
  • FDA. Psychopharmacological drugs advisory committee: briefing document for NDA 20-644 (sertindole). 2009. [cited 2016 Feb 17]. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM161901.pdf
  • Polcwiartek C, Sneider B, Graff C, et al. The cardiac safety of aripiprazole treatment in patients at high risk for torsade: a systematic review with a meta-analytic approach. Psychopharmacology (Berl). 2015;232:3297–3308.
  • Nielsen J, Skadhede S, Correll CU. Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naïve schizophrenia patients. Neuropsychopharmacology. 2010;35:1997–2004.
  • Pae C-U. A review of the safety and tolerability of aripiprazole. Expert Opin Drug Saf. 2009;8:373–386.
  • Dargani NV, Malhotra AK. Safety profile of iloperidone in the treatment of schizophrenia. Expert Opin Drug Saf. 2014;13:241–246.
  • Citrome L. Asenapine review, part II: clinical efficacy, safety and tolerability. Expert Opin Drug Saf. 2014;13:803–830.
  • Nielsen J. QTc prolongation and clozapine: fact or artefact? Aust N Z J Psychiatry. 2012;46:793–794.
  • ICH. The clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. 2005. [cited 2016 Feb 17]. Available from: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E14/E14_Guideline.pdf
  • Bouvy JC, Koopmanschap MA, Shah RR, et al. The cost-effectiveness of drug regulation: the example of thorough QT/QTc studies. Clin Pharmacol Ther. 2012;91:281–288.
  • 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;35:1306–1315.
  • Porthan K, Viitasalo M, Jula A, et al. Predictive value of electrocardiographic QT interval and T-wave morphology parameters for all-cause and cardiovascular mortality in a general population sample. Heart Rhythm. 2009;6:1202–1208.
  • Rabkin SW, Cheng XB. Nomenclature, categorization and usage of formulae to adjust QT interval for heart rate. World J Cardiol. 2015;7:315–325.
  • Nielsen J, Wang F, Graff C, et al. QT dynamics during treatment with sertindole. Ther Adv Psychopharmacol. 2015;5:26–31.
  • Nielsen J, Matz J, Mittoux A, et al. Cardiac effects of sertindole and quetiapine: analysis of ECGs from a randomized double-blind study in patients with schizophrenia. Eur Neuropsychopharmacol. 2015;25:303–311.
  • Nielsen J, Andersen MP, Graff C, et al. The effect of sertindole on QTD and TPTE. Acta Psychiatr Scand. 2010;121:385–388.
  • Graff C, Struijk JJ, Matz J, et al. Covariate analysis of QTc and T-wave morphology: new possibilities in the evaluation of drugs that affect cardiac repolarization. Clin Pharmacol Ther. 2010;88:88–94.
  • Nielsen J, Graff C, Hardahl T, et al. Sertindole causes distinct electrocardiographic T-wave morphology changes. Eur Neuropsychopharmacol. 2009;19:702–707.
  • Graff C, Matz J, Christensen EB, et al. Quantitative analysis of T-wave morphology increases confidence in drug-induced cardiac repolarization abnormalities: evidence from the investigational IKr inhibitor Lu 35-138. J Clin Pharmacol. 2009;49:1331–1342.
  • Graff C, Andersen MP, Xue JQ, et al. Identifying drug-induced repolarization abnormalities from distinct ECG patterns in congenital long QT syndrome: a study of sotalol effects on T-wave morphology. Drug Saf. 2009;32:599–611.
  • Kanters JK, Haarmark C, Vedel-Larsen E, et al. T(peak)T(end) interval in long QT syndrome. J Electrocardiol. 2008;41:603–608.
  • DSKP. [Clinically relevant psychopharmacological interactions]. 2010. [cited 2016 Feb 17]. Available from: http://www.psykofarmakologi.dk/actioncards/interaktioner.html
  • Brown CS, Farmer RG, Soberman JE, et al. Pharmacokinetic factors in the adverse cardiovascular effects of antipsychotic drugs. Clin Pharmacokinet. 2004;43:33–56.
  • Takeuchi H, Suzuki T, Remington G, et al. Antipsychotic polypharmacy and corrected QT interval: a systematic review. Can J Psychiatry. 2015;60:215–222.
  • Gallego JA, Nielsen J, De Hert M, et al. Safety and tolerability of antipsychotic polypharmacy. Expert Opin Drug Saf. 2012;11:527–542.
  • Sicouri S, Antzelevitch C. Sudden cardiac death secondary to antidepressant and antipsychotic drugs. Expert Opin Drug Saf. 2008;7:181–194.
  • Adler A, Topaz G, Heller K, et al. Fever-induced Brugada pattern: how common is it and what does it mean? Heart Rhythm. 2013;10:1375–1382.
  • Garnier F, Mathe A, Bruyeres R. Images in cardiology: electrical aspects of Brugada: hyperkalaemia and intoxication with phenothiazines. Heart. 2008;94:1578.
  • Roberts-Thomson KC, Teo KS, Young GD. Drug-induced Brugada syndrome with ST-T wave alternans and long QT. Intern Med J. 2007;37:199–200.
  • Copetti R, Proclemer A, Pillinini PP. Brugada-like ECG abnormalities during thioridazine overdose. Br J Clin Pharmacol. 2005;59:608.
  • Rouleau F, Asfar P, Boulet S, et al. Transient ST segment elevation in right precordial leads induced by psychotropic drugs: relationship to the Brugada syndrome. J Cardiovasc Electrophysiol. 2001;12:61–65.
  • Chong JH, Eversheim F. Clozapine-induced reversible Brugada Syndrome. GSTF J Adv Med Res (JAMR). 2015;1:18–20.
  • Leung JY, Barr AM, Procyshyn RM, et al. Cardiovascular side-effects of antipsychotic drugs: the role of the autonomic nervous system. Pharmacol Ther. 2012;135:113–122.
  • Chavez B, Poveda RA. Efficacy with high-dose aripiprazole after olanzapine-related metabolic disturbances. Ann Pharmacother. 2006;40:2265–2268.
  • Feinstein RE. Cardiovascular effects of novel antipsychotic medications. Heart Dis. 2002;4:184–190.
  • Nielsen J, Correll CU, Manu P, et al. Termination of clozapine treatment due to medical reasons: when is it warranted and how can it be avoided? J Clin Psychiatry. 2013;74:603–613. quiz 13.
  • Polcwiartek C, Nielsen J. The clinical potentials of adjunctive fluvoxamine to clozapine treatment: a systematic review. Psychopharmacology (Berl). 2016;233:741–750.
  • Buckley NA, Sanders P. Cardiovascular adverse effects of antipsychotic drugs. Drug Saf. 2000;23:215–228.
  • Gugger JJ. Antipsychotic pharmacotherapy and orthostatic hypotension: identification and management. CNS Drugs. 2011;25:659–671.
  • Sørensen HJ, Jensen SO, Nielsen J. Schizophrenia, antipsychotics and risk of hip fracture: a population-based analysis. Eur Neuropsychopharmacol. 2013;23:872–878.
  • Gareri P, De Fazio P, Stilo M, et al. Conventional and atypical antipsychotics in the elderly: a review. Clin Drug Investig. 2003;23:287–322.
  • Gareri P, De Fazio P, Russo E, et al. The safety of clozapine in the elderly. Expert Opin Drug Saf. 2008;7:525–538.
  • Henderson DC, Daley TB, Kunkel L, et al. Clozapine and hypertension: a chart review of 82 patients. J Clin Psychiatry. 2004;65:686–689.
  • Lund BC, Perry PJ, Brooks JM, et al. Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach. Arch Gen Psychiatry. 2001;58:1172–1176.
  • Khasawneh FT, Shankar GS. Minimizing cardiovascular adverse effects of atypical antipsychotic drugs in patients with schizophrenia. Cardiol Res Pract. 2014;2014:273060.
  • Bodén R, Edman G, Reutfors J, et al. A comparison of cardiovascular risk factors for ten antipsychotic drugs in clinical practice. Neuropsychiatr Dis Treat. 2013;9:371–377.
  • Brauer R, Douglas I, Smeeth L. The association between antipsychotic agents and the risk of myocardial infarction: a systematic review. Br J Clin Pharmacol. 2011;72:871–878.
  • Wu S-I, Kao K-L, Chen S-C, et al. Antipsychotic exposure prior to acute myocardial infarction in patients with serious mental illness. Acta Psychiatr Scand. 2015;131:213–222.
  • Brauer R, Smeeth L, Anaya-Izquierdo K, et al. Antipsychotic drugs and risks of myocardial infarction: a self-controlled case series study. Eur Heart J. 2015;36:984–992.
  • Lin S-T, Chen -C-C, Tsang H-Y, et al. Association between antipsychotic use and risk of acute myocardial infarction: a nationwide case-crossover study. Circulation. 2014;130:235–243.
  • Nielsen J, Juel J, Alzuhairi KS, et al. Unrecognised myocardial infarction in patients with schizophrenia. Acta Neuropsychiatr. 2015;27:106–112.
  • Fitzsimons J, Berk M, Lambert T, et al. A review of clozapine safety. Expert Opin Drug Saf. 2005;4:731–744.
  • Ronaldson KJ, Fitzgerald PB, McNeil JJ. Clozapine-induced myocarditis, a widely overlooked adverse reaction. Acta Psychiatr Scand. 2015;132:231–240.
  • Vang T, Rosenzweig M, Bruhn CH, et al. Eosinophilic myocarditis during treatment with olanzapine – report of two possible cases. BMC Psychiatry. 2016;16:70.
  • Dean CE, Thuras PD. Mortality and tardive dyskinesia: long-term study using the US National Death Index. Br J Psychiatry. 2009;194:360–364.
  • Nielsen J, Young C, Ifteni P, et al. Worldwide differences in regulations of clozapine use. CNS Drugs. 2016;30:149–161.
  • Ronaldson KJ, Fitzgerald PB, Taylor AJ, et al. A new monitoring protocol for clozapine-induced myocarditis based on an analysis of 75 cases and 94 controls. Aust N Z J Psychiatry. 2011;45:458–465.
  • Haffner SM, Lehto S, Rönnemaa T, et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–234.
  • Musil R, Obermeier M, Russ P, et al. Weight gain and antipsychotics: a drug safety review. Expert Opin Drug Saf. 2015;14:73–96.
  • Werner F-M, Coveñas R. Safety of antipsychotic drugs: focus on therapeutic and adverse effects. Expert Opin Drug Saf. 2014;13:1031–1042.

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