Prevalence of QTc interval prolongation and its associated risk factors among psychiatric patients: a prospective observational study

Ali et al. BMC Psychiatry (2020) 20:277 https://doi.org/10.1186/s12888-020-02687-w RESEARCH ARTICLE Open Access Prevalence of QTc interval prolongation and its associated risk factors among psychiatric patients: a prospective observational study Zahid Ali1 , Mohammad Ismail1* , Zahid Nazar2, Fahadullah Khan1, Qasim Khan3 and Sidra Noor1 Abstract Background: QT interval prolongation is a growing concern worldwide, posing psychiatric patients to lifethreatening fatal arrhythmias i.e., torsade de pointes. This study aimed to identify the prevalence of QT interval prolongation, its associated risk factors and prescribing patterns of QT prolonging drugs among psychiatric patients. Method: A prospective observational study was conducted that included psychiatric patients from a tertiary care hospital and a psychiatry clinic in Peshawar, Khyber Pakhtunkhwa, Pakistan. Electrocardiogram was recorded of those patients who were using psychotropic medications for ≥7 days, aged 18 years or more, and of either gender, male or female. The Fredericia correction formula was used for measuring QTc values (corrected QT). Chi-square test was applied to estimate differences between patients with or without prolonged QTc interval whereas, logistic regression analysis was performed to identify various predictors of QT interval prolongation. Results: Out of 405 patients, the QTc interval was prolonged in 23 (5.7%) patients including 1 (0.2%) patient with highly abnormal prolonged QTc interval (> 500 ms). QT drugs (91.6%), female sex (38.7%) and hypertension (10.6%) were the most common QT prolonging risk factors. Prolonged QTc interval was significantly higher among male patients (p = 0.007). Conclusion: In the present study, QT interval prolongation was observed in a considerable number of psychiatric patients. While, the high prevalence of QT prolonging risk factors among these patients warrants the increased risk of fatal arrhythmias. Therefore, risk assessment and electrocardiographic monitoring, and prescription of safer alternatives are highly recommended. Keywords: QT interval prolongation, Prevalence, Risk factors, Torsade de pointes, Psychotropics, Psychiatry Background QT interval prolongation (QTIP) is a well-known surrogate marker for torsades de pointes (TdP), a lifethreatening ventricular arrhythmia, that may result in sudden cardiac death [1–4]. QTIP is a consequence of * Correspondence: 1 Department of Pharmacy, University of Peshawar, Peshawar, Khyber Pakhtunkhwa, Pakistan Full list of author information is available at the end of the article abnormality in the ion channels of the heart such as potassium, sodium, and calcium channels [5]. Cardiac channel abnormalities may be congenital or acquired, the latter is more common and is often associated with drugs [6]. Psychiatric patients are at higher risk of drug induced TdP because majority of the psychotropic agents (antipsychotics and antidepressants) are notorious for prolonging the QT interval [7]. The risk is further © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Ali et al. BMC Psychiatry (2020) 20:277 enhanced in patients with other QT prolonging risk factors such as bradycardia, diabetes mellitus, hypertension, advance age, female sex, underlying heart diseases and illicit drugs use [8–10]. Psychiatric patients are often exposed to psychotropic polypharmacy [11, 12], high dose therapy and illicit drug use, which considerably increase the probability of exposure to QT prolonging drugs and QT drug-drug interactions (QT-DDIs) [10, 13]. In psychiatry settings, polypharmacy is a traditional and old practice that is increasingly becoming a norm rather than exception. In a review on polypharmacy in psychiatry, Kukreja et al. reported the prevalence of psychiatric polypharmacy (≥2 drugs) between 13 and 90% [14]. Another study reported, 19% prevalence of multi-class psychotropic polypharmacy among children and adolescents [15]. According to a study, since 1974 prescriptions containing ≥3 drugs increased from 5% to 40% in 1995 [16]. In addition, among psychiatric patients, the higher risk of QTIP is also due to frequent QT prolonging antidepressant and antipsychotic combinations [4, 17]. In most clinical conditions, > 1 psychotropic drug is indicated [18, 19]. In some clinical situations, compared to a single antidepressant or antipsychotic drug, patients with psychiatric illnesses significantly improved after adding a second psychotropic drug in the prescription [20–23]. However, another study also reported significant increase in psychotropic polypharmacy in a psychiatry setting with many combinations of unproven efficacy that are not supported by controlled clinical trials [11]. Recently, a study reported higher prevalence of contraindicated combinations with two antidepressants (escitalopram or citalopram) among hospitalized patients [24]. Using > 1 QT prolonging medications simultaneously increase the risk of life-threatening ventricular arrhythmias [25]. Psychiatric polypharmacy, psychotropic QT prolonging drug combinations and high dose therapies are inevitable in such a population due to multiple illnesses and tolerance to the recommended dose of therapy [13, 26, 27]. The increased prevalence of polypharmacy, contraindicated combinations and high dose therapy coupled with poor access to health care facilities increase the risk of QTIP associated morbidity and mortality [14, 24, 28]. Despite considerable safety concern for QTIP associated with psychotropic drugs, studies are scarce regarding the prevalence of QTIP and its associated risk factors among psychiatric patients, particularly in the developing countries. Moreover, electrocardiographic monitoring for QTIP is not performed in routine clinical practice despite the known risk of QTIP and TdP with psychotropic agents [9, 29]. Therefore, this study aimed to identify the prevalence of QTIP, its associated risk Page 2 of 7 factors and presc (...truncated)