QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy

Springer Science and Business Media LLC - Tập 4 - Trang 1-6 - 2005
Michela Sala1, Alessandro Vicentini2, Paolo Brambilla3, Cristina Montomoli4, Jigar RS Jogia5, Eduardo Caverzasi1, Alberto Bonzano1, Marco Piccinelli6, Francesco Barale1, Gaetano M De Ferrari2
1Department of Health Sciences-Section of Psychiatry, IRCCS Policlinico S. Matteo, University of Pavia, School of Medicine, Pavia, Italy
2Department of Cardiology, IRCCS Policlinico S. Matteo, University of Pavia, School of Medicine, Pavia, Italy
3Department of Pathology and Experimental and Clinical Medicine, Section of Psychiatry, University of Udine School of Medicine, Udine, Italy
4Department of Health Sciences, University of Pavia, Pavia, Italy
5Section of Neurobiology of Psychosis, Institute of Psychiatry, London, UK
6Psychiatry Unit, Azienda Ospedaliera Universitaria Ospedale di Circolo e Fondazione Macchi di Varese, Presidio Ospedaliero del Verbano, Italy

Tóm tắt

Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc) exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine) and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine) with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine) or lithium. An Electrocardiogram (ECG) was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms) however this was not the case in Group 1 (-1 ± 30 ms) (Repeated measures ANOVA p < 0,01). Furthermore we found a significant difference in the number of patients who exceeded the threshold of borderline QTc interval value (450 ms) between the two groups, with seven patients in Group 2 (38%) compared to one patient in Group 1 (7%) (Fisher Exact Text, p < 0,05). No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a combined treatment of antipsychotic and antidepressant agents.

Tài liệu tham khảo

Haddad PM, Anderson IM: Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs. 2002, 62: 1649-71. Committee for Proprietary Medicinal Products: Point to consider: the assessment of the potential for QT interval prolongation by non cardiovascular medicinal products. December 17, 1997, [http://www.emea.eu.int/pdfs/human/swp/098696en.pdf] Abi-Gerges N, Philp K, Pollard C, Wakefield I, Hammond TG, Valentin JP: Sex differences in ventricular repolarization: from cardiac electrophysiology to Torsades de Pointes. Fundam Clin Pharmacol. 2004, 18: 139-51. 10.1111/j.1472-8206.2004.00230.x. Angelink M, Majewski T, Wurthmann C, Lukas K, Ullrich H, Linka T, Klieser E: Effects of newer atypical antipsychotics on autonomic neurocardiac function: a comparison between amisulpride, olanzapine, setindole, and clozapine. J Clin Psychopharmacology. 2001, 21: 8-13. 10.1097/00004714-200102000-00003. Czekalla J, Kollack-Walker S, Beasley CM: Cardiac Safety parameters of olanzapine: comparison with other atypical and typical antipsychotics. J Clin Psychiatry. 2001, 62 (Suppl 2): 35-40. Food and Drug Administration: Psychopharmacological Drugs Advisory Committee. Briefing Document for Zeldox Capsules (ziprasidone HCl). July 19, 2000 http://www.fda.gov/ohrms/dockets/ac/00/backgrd/3619b1a.pdf, http://www.fda.gov/ohrms/dockets/ac/00/backgrd/3619b1b.pdf Food and Drug Administration: Center for Drug Evaluation and Research Psychopharmacological Drugs Advisory Commitee. Meeting Transcript. July 19, 2000 http://www.fda.gov/ohrms/dockets/ac/00/transcripts/3619t1a.pdf, http://www.fda.gov/ohrms/dockets/ac/00/transcripts/3619t1b.pdf, http://www.fda.gov/ohrms/dockets/ac/00/transcripts/3619t1c.pdf Elming H, Sonne J, Lublin HKF: The importance of the QT interval: a review of the literature. Acta Psychiatr Scand. 2003, 107: 96-101. 10.1034/j.1600-0447.2003.00061.x. Haverkamp W, Breithardt G, Camm AJ, Janse MJ, Rosen MR, Antzelevitch C, Escande D, Franz M, Malik M, Moss A, Shah R: The potential for QT prolongation and pro-arrhythmia by non-anti-arrhythmic drugs: Clinical and regulatory implications Report on a Policy Conference of the European Society of Cardiology. Cardiovasc Res. 2000, 47: 219-33. 10.1016/S0008-6363(00)00119-X. Rodriguez de la Torre B, Dreher J, Malevany I, Bagli M, Kolbinger M, Omran H: Serum Levels and cardiovascular effects of tricyclic antidepressants and selective serotonine reuptake inhibitors in depressed patients. Ther Drug Monit. 2001, 23: 435-440. 10.1097/00007691-200108000-00019. Tie H, Walker BD, Valenzuela SM, Breit SN, Campbell TJ: The Heart of Psychotropic drug therapy. Lancet. 2000, 355: 1825- Glassmann AH: Clinical Management of cardiovascular risks during treatment with psychotropic drugs. J Clin Psychiatry. 2002, 63 (Suppl 9): 12-7. Teschemacher AG, Seward EP, Hancox JC, Witchel HJ: Inhibition of the current of heterologously expressed HERG potassium channels by imipramine and amitriptyline. Br J Pharmacol. 1999, 128: 479-485. 10.1038/sj.bjp.0702800. Mitcheson JS: Drug binding to HERG channels:evidence for a "non-aromatic" binding site for fluvoxamine. Br J Pharmacol . 2003, 139: 883-884. 10.1038/sj.bjp.0705336. Milnes JT, Crociani O, Arcangeli A, Hancox JC, Witchel HJ: Blockade of HERG potassium currents by fluvoxamine: incomplete attenuation by S6 mutations at F656 or Y652. Br J Pharmacol. 2003, 139: 887-898. 10.1038/sj.bjp.0705335. Witchel HJ, Pabbathi VK, Hofmann G, Paul AA, Hancox JC: Inhibitory actions of the selective serotonine re-uptake inhibitor citalopram on HERG and ventricular L-type calcium currents. FEBS. 2002, 512: 59-66. 10.1016/S0014-5793(01)03320-8. Thomas D, Gut B, Wendt-Nordahl G, Kiehn J: The antidepressant drug fluoxetine is an inhibitor of human ether-a-go-go-related gene (HERG) potassium channels. J Pharmacol Exp Ther. 2002, 300: 543-8. 10.1124/jpet.300.2.543. Reilly JG, Ayis SA, Ferrier IN, Jones SJ, Thomas SHL: QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet. 2000, 355: 1048-52. 10.1016/S0140-6736(00)02035-3. Piccinelli M: Antipsicotici Vademecum per lo psichiatra italiano. Edited by: Sprinter. 2004 Facciollà G, Scordo MG: Citocromo P450 e interazioni tra farmaci. [http://www.farmacovigilanza.org] Idle JR: The Heart of Psychotropic drug therapy. Lancet. 2000, 355: 1824- Harringan EP, Miceli JJ, Anziano R, Watsky E, Reeves KR, Cutler NR, Sramek J, Shiovitz T, Middle M: A randomized evaluation of the effects of six antipsychotic agent on the QTc, in the absence and presence of metabolic inhibition. J Clin Psychopharmacol. 2004, 24: 62-9. 10.1097/01.jcp.0000104913.75206.62. Kongsamut S, Kang J, Chen XL, Roehr J, Rampe D: A comparison of the receptor binding and HERG channels affinities for a series of antipsychotic drugs. Eur J Pharmacol. 2002, 450: 37-41. 10.1016/S0014-2999(02)02074-5. Magyar J, Banyasz T, Bagi Z, Pacher P, Szentandrassy N, Fülöp L, Kecskemeti V, Nanasi PP: Electrophysiological effects of risperidone in mammalian cardiac cells. Naunyn-Schmiedeberg's Arch Pharmacol. 2002, 366: 350-6. 10.1007/s00210-002-0595-1. Ruschena D, Mullen PE, Burgess P, Cordner SM, Barry-Walsh J, Drummer OH, Palmer S, Browne C, Wallace C: Sudden death in psychiatric patients. Br J Psychiatry. 1998, 172: 331-6. Politi P, Piccinelli M, Klersy C, Madini S, Segagni LG, Fratti C, Barale F: Mortality in psychiatric patients 5 to 21 years after hospital admission in Italy. Psychol Med. 2002, 32: 227-37. Hannerz H, Borga P: Mortality among persons with a history as psychiatric inpatients with functional psychosis. Soc Psychiatry Psychiatr Epidemiol. 2000, 35: 380-7. 10.1007/s001270050254. Roden DM: Taking the "idio" out of "idiosyncratic": predicting torsades se pointes. PACE. 1998, 21: 1029-34. Redfern WS, Carlsson L, Davis AS, Lynch WG, MacKenzie I, Palethorpe S: Relationship between preclinical 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. 10.1016/S0008-6363(02)00846-5. Hatta K, Takahashi T, Nakamura H, Yamashiro H, Yonezawa Y: Prolonged QT interval in acute psychotic patients. Psychiatry Res. 2000, 94: 279-85. 10.1016/S0165-1781(00)00152-9.