Prevalence of Drugs and Drug Combinations that Increase Risk of Prolonged QT Time Among People with Major Neurocognitive Disorder Living in Sweden: A Cross-Sectional Registry Study

Abstract

Background People with major neurocognitive disorder might be susceptible to drug-induced QT interval prolongation due to the presence of a number of concomitant risk factors. Objective The aim of this study was to investigate the prevalence of QT-prolonging drugs and QT-prolonging drug-drug interactions and associated factors among older people with major neurocognitive disorder. Methods In this register-based study, we obtained information regarding QT-prolonging drug use in a large population of older people with major neurocognitive disorder, through record linkage between the Swedish registry for cognitive/dementia disorders, and the Swedish Prescribed Drug Register. QT-prolonging drugs were identified according to the CredibleMeds online database and interactions using the Janusmed interaction database. Drug use was defined as one or more filled prescriptions during a 6-month timeframe, July 01 to December 31, 2017. Associations between people with a QT-prolonging drug and the factors of age and gender were analysed through multiple logistic regression. Results Of 35,212 people included in the study, 41.6% had one or more QT-prolonging drug prescribed. The most commonly prescribed drug was donepezil, with a prevalence of 25.0%, followed by citalopram and escitalopram, representing 14.5% and 3.9% of prescriptions in the study population, respectively. Significant associations were found between QT-prolonging drug use and the factors of younger age and female gender. The most prevalent interaction was between citalopram and donepezil (2.7%), followed by the combination of escitalopram and donepezil (0.7%). Conclusions In this population of older people with major neurocognitive disorder, QT-prolonging drugs and interactions that increase the risk of torsade de pointes were prevalent. Due to the presence of many risk factors in this population, it is important to continuously evaluate current QT-prolonging drugs and concomitant drug treatment in each individual.

Escitalopram-induced sinus bradycardia in coronary heart disease combined with depression: a case report and review of literature

“…Citalopram consists of two stereostructures, one stereoisomer is S-Citalopram (escitalopram) and the other isomer is R-Citalopram (no drug activity), each of which is 50%. The cross-sectional registry study found that the prevalence of QT-prolonging drugs included citalopram and escitalopram, which represent 14.5% and 3.9% of the study population, respectively ( 39 ), confirming that escitalopram had fewer adverse reactions than citalopram. However, a recent systematic review and meta-analysis involving 1,141 patients (573 experimental and 568 control) in randomized controlled trials showed that citalopram has positive effects on the left ventricular ejection fraction and N-terminal pro-B-type natriuretic peptide in patients with depression combined with chronic heart failure; meanwhile, no obvious adverse drug reactions were observed ( 40 ).…”

“…In addition to bradycardia during escitalopram use, the first-degree atrioventricular block and second-degree type I atrioventricular block were also detected by electrocardiogram in this case. In vivo study has demonstrated that escitalopram treatment could cause a decrease in heart rate, which manifests as a significant decrease in sympathetic components and a significant increase in parasympathetic components of the autonomic nervous imbalance (38). This may be a possible pathogenesis of escitalopram-related bradycardia.…”

Cholinesterase inhibitors-associated torsade de pointes/QT prolongation: a real-world pharmacovigilance study

“…Generally, the risk of QT prolongation is considered higher in women, and studies have reported the risk of antipsychotic drugs on QT interval prolongation in women ( Suzuki et al, 2013 ). A large cross-sectional registry study in Sweden showed that in the elderly population with severe neurocognitive impairment, the use of drugs that prolong the QT interval was significantly associated with factor in women ( Gustafsson et al, 2023 ). Studies have shown that females are at increased risk for QT prolongation compared to males, likely due to their longer baseline QT intervals and gender-specific differences in cardiac delayed rectifier potassium channel expression regulated by estrogen ( Rabkin, 2015 ).…”