Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-15T21:14:53.743Z Has data issue: false hasContentIssue false
  • English
  • Français

Prevalence and correlates of QTc prolongation in Italian psychiatric care: cross-sectional multicentre study

Published online by Cambridge University Press:  15 October 2015

M. Nosè ,
I. Bighelli ,
M. Castellazzi ,
G. Martinotti ,
G. Carrà ,
C. Lucii ,
G. Ostuzzi ,
F. Sozzi ,
C. Barbui  and
the STAR NETWORK GROUP
M. Nosè*
Affiliation:
WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy
I. Bighelli
Affiliation:
WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy
M. Castellazzi
Affiliation:
WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy
G. Martinotti
Affiliation:
Department of Neuroscience, Imaging and Clinical Sciences, University of Chieti, Chieti, Italy
G. Carrà
Affiliation:
Department of Surgery and Interdisciplinary Medicine, University of Milano Bicocca, Milan, Italy
C. Lucii
Affiliation:
Department of Mental Health, Siena, Italy
G. Ostuzzi
Affiliation:
WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy
F. Sozzi
Affiliation:
WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy
C. Barbui
Affiliation:
WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Verona, Italy
*
*Address for correspondence: M. Nosè, Department of Public Health and Community Medicine, Section of Psychiatry, University of Verona, Policlinico GB Rossi, Piazzale Scuro 10, 37134 Verona, Italy. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Aims.

In recent years several warnings have been issued by regulatory authorities on the risk of electrocardiogram abnormalities in individuals exposed to psychotropic drugs. As a consequence of these warnings, monitoring of the QT interval corrected for heart rate (QTc) has become increasingly common. This study was conducted to measure the frequency of QTc prolongation in unselected psychiatric patients, and to document the associated factors using a cross-sectional approach.

Method.

The study was carried out in 35 Italian psychiatric services that are part of the STAR (Servizi Territoriali Associati per la Ricerca) Network, a research group established to produce scientific knowledge by collecting data under ordinary circumstances. During a three-month period, a consecutive unselected series of both in- and out-patients were enrolled if they performed an ECG during the recruitment period and were receiving psychotropic drugs on the day ECG was recorded.

Results.

During the recruitment period a total of 2411 patients were included in the study. The prevalence of QTc prolongation ranged from 14.7% (men) and 18.6% (women) for the cut-off of 450 ms, to 1.26% (men) and 1.01% (women) for the cut-off of 500 ms. In the multivariate model conducted in the whole sample of patients exposed to psychotropic drugs, female sex, age, heart rate, alcohol and/or substance abuse, cardiovascular diseases and cardiovascular drug treatment, and drug overdose were significantly associated with QTc prolongation. In patients exposed to antipsychotic drugs, polypharmacy was positively associated with QTc prolongation, whereas use of aripiprazole decreased the risk. In patients exposed to antidepressant drugs, use of citalopram, citalopram dose and use of haloperidol in addition to antidepressant drugs, were all positively associated with QTc prolongation.

Conclusions.

The confirmation of a link between antipsychotic polypharmacy and QTc prolongation supports the current guidelines that recommend avoiding the concurrent use of two or more antipsychotic drugs, and the confirmation of a link between citalopram and QTc prolongation supports the need for routine QTc monitoring. The relatively low proportion of patients with QTc prolongation not only suggests compliance with current safety warnings issued by regulatory authorities, but also casts some doubts on the clinical relevance of QTc prolongation related to some psychotropic drugs.

Keywords

Antidepressantantipsychoticadverse effectpsychotropic drugs
Type
Original Articles
Information
Epidemiology and Psychiatric Sciences , Volume 25 , Issue 6 , December 2016 , pp. 532 - 540
Copyright
Copyright © Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Beach, SR, Celano, CM, Noseworthy, PA, Januzzi, JL, Huffman, JC (2013). QTc prolongation, torsades de pointes, and psychotropic medications. Psychosomatics 54, 1–13.Google Scholar
Beach, SR, Kostis, WJ, Celano, CM, Januzzi, JL, Ruskin, JN, Noseworthy, PA, Huffman, JC (2014). Meta-analysis of selective serotonin reuptake inhibitor-associated QTc prolongation. Journal of Clinical Psychiatry 75, e441–e449.Google Scholar
Castro, VM, Clements, CC, Murphy, SN, Gainer, VS, Fava, M, Weilburg, JB, Erb, JL, Churchill, SE, Kohane, IS, Iosifescu, DV, Smoller, JW, Perlis, RH (2013). QT interval and antidepressant use: a cross sectional study of electronic health records. British Medical Journal 346, f288.Google Scholar
Conti, V, Lora, A, Cipriani, A, Fortino, I, Merlino, L, Barbui, C (2012 ). Persistence with pharmacological treatment in the specialist mental healthcare of patients with severe mental disorders. European Journal of Clinical Pharmacology.Google Scholar
Efron, B, Tibshirani, R (1986). Bootstrap methods of standard errors, confidence intervals, and other measures of statistical accuracy. Statistical Science 1, 54–77.Google Scholar
Girardin, FR, Gex-Fabry, M, Berney, P, Shah, D, Gaspoz, JM, Dayer, P (2013). Drug-induced long QT in adult psychiatric inpatients: the 5-year cross-sectional ECG screening outcome in Psychiatry study. American Journal of Psychiatry 170, 1468–1476.Google Scholar
Hasnain, M, Vieweg, WV (2014). QTc interval prolongation and torsade de pointes associated with second-generation antipsychotics and antidepressants: a comprehensive review. CNS Drugs 28, 887–920.CrossRefGoogle ScholarPubMed
Kogut, C, Crouse, EB, Vieweg, WV, Hasnain, M, Baranchuk, A, Digby, GC, Koneru, JN, Fernandez, A, Deshmukh, A, Hancox, JC, Pandurangi, AK (2013). Selective serotonin reuptake inhibitors and torsade de pointes: new concepts and new directions derived from a systematic review of case reports. Therapeutic Advances in Drug Safety 4, 189–198.Google Scholar
Leucht, S, Cipriani, A, Spineli, L, Mavridis, D, Orey, D, Richter, F, Samara, M, Barbui, C, Engel, RR, Geddes, JR, Kissling, W, Stapf, MP, Lassig, B, Salanti, G, Davis, JM (2013). Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 382, 951–962.Google Scholar
Meyer-Massetti, C, Cheng, CM, Sharpe, BA, Meier, CR, Guglielmo, BJ (2010). The FDA extended warning for intravenous haloperidol and torsades de pointes: how should institutions respond? Journal of Hospital Medicine 5, E8–16.Google Scholar
Nose, M, Barbui, C (2008). A simple approach to manage dosages in drug-epidemiology research. Epidemiologia e Psichiatria Sociale 17, 186–187.Google Scholar
Nose, M, Barbui, C (2014). Do antidepressants prolong the QT interval? Epidemiology and Psychiatric Science 23, 19–20.Google Scholar
Nose, M, Tansella, M, Thornicroft, G, Schene, A, Becker, T, Veronese, A, Leese, M, Koeter, M, Angermeyer, M, Barbui, C (2008). Is the defined daily dose system a reliable tool for standardizing antipsychotic dosages? International Clinical Psychopharmacology 23, 287–290.Google Scholar
Pasquier, M, Pantet, O, Hugli, O, Pruvot, E, Buclin, T, Waeber, G, Aujesky, D (2012). Prevalence and determinants of QT interval prolongation in medical inpatients. Internal Medicine Journal 42, 933–940.Google Scholar
Ramos-Rios, R, Rrojo-Romero, M, Paz-Silva, E, Carballal-Calvo, F, Bouzon-Barreiro, JL, Seoane-Prado, J, Codesido-Barcala, R, Crespi-Armenteros, A, Fernandez-Perez, R, Lopez-Morinigo, JD, Tortajada-Bonaselt, I, Diaz, FJ, De, LJ (2010). QTc interval in a sample of long-term schizophrenia inpatients. Schizophrenia Research 116, 35–43.Google Scholar
Reilly, JG, Ayis, SA, Ferrier, IN, Jones, SJ, Thomas, SH (2000). QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Lancet 355, 1048–1052.Google Scholar
Sadanaga, T, Sadanaga, F, Yao, H, Fujishima, M (2004). Abnormal QT prolongation and psychotropic drug therapy in psychiatric patients: significance of bradycardia-dependent QT prolongation. Journal of Electrocardiology 37, 267–273.CrossRefGoogle ScholarPubMed
Sala, M, Vicentini, A, Brambilla, P, Montomoli, C, Jogia, JR, Caverzasi, E, Bonzano, A, Piccinelli, M, Barale, F, De Ferrari, GM (2005). QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy v. polytherapy. Annals of General Psychiatry 4, 1.Google Scholar
Taylor, DM (2003). Antipsychotics and QT prolongation. Acta Psychiatrica Scandinavica 107, 85–95.Google Scholar
van Haelst, IM, van Klei, WA, Doodeman, HJ, Warnier, MJ, De Bruin, ML, Kalkman, CJ, Egberts, TC (2014). QT interval prolongation in users of selective serotonin reuptake inhibitors in an elderly surgical population: a cross-sectional study. Journal of Clinical Psychiatry 75, 15–21.Google Scholar
Vieweg, WV, Hasnain, M, Howland, RH, Hettema, JM, Kogut, C, Wood, MA, Pandurangi, AK (2012). Citalopram, QTc interval prolongation, and torsade de pointes. How should we apply the recent FDA ruling? American Journal of Medicine 125, 859–868.Google Scholar