An analysis of QTc prolongation with atypical antipsychotic medications and selective serotonin reuptake inhibitors using a large ECG record database

Park, Sang‐In; An, Hyungmi; Kim, Anhye; Jang, In‐Jin; Yu, Kyung‐Sang; Chung, Jae Yong

doi:10.1080/14740338.2016.1199681

Cited by 8 publications

(6 citation statements)

References 35 publications

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“…After examining the association of the QTc interval with certain drugs, Yun et al [ 11 ] suggested that famotidine administration can prolong the QTc interval and increase the proarrhythmic potential. Additionally, Park et al [ 13 ] concluded that selective serotonin reuptake inhibitors are less likely to be associated with QTc interval prolongation. The ECG-ViEW II contains previous ECG-ViEW data and an additional 270 thousand ECGs, allowing researchers to study the relationship between the QT interval and drug administration.…”

Section: Resultsmentioning

confidence: 99%

ECG-ViEW II, a freely accessible electrocardiogram database

et al. 2017

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The Electrocardiogram Vigilance with Electronic data Warehouse II (ECG-ViEW II) is a large, single-center database comprising numeric parameter data of the surface electrocardiograms of all patients who underwent testing from 1 June 1994 to 31 July 2013. The electrocardiographic data include the test date, clinical department, RR interval, PR interval, QRS duration, QT interval, QTc interval, P axis, QRS axis, and T axis. These data are connected with patient age, sex, ethnicity, comorbidities, age-adjusted Charlson comorbidity index, prescribed drugs, and electrolyte levels. This longitudinal observational database contains 979,273 electrocardiograms from 461,178 patients over a 19-year study period. This database can provide an opportunity to study electrocardiographic changes caused by medications, disease, or other demographic variables. ECG-ViEW II is freely available at http://www.ecgview.org.

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Section: Resultsmentioning

confidence: 99%

ECG-ViEW II, a freely accessible electrocardiogram database

et al. 2017

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“…Although meta-analyses have indicated that different antipsychotics have different effects on QTc prolongation, 5 several studies based on real-world data showed no association between atypical antipsychotics use and QTc prolongation. 20,21,30,31 The association between antipsychotics and QTC prolongation needs to be further explored with a large longitudinal follow-up study.…”

Section: Discussionmentioning

confidence: 99%

A Real-World Study of Risk Factors for QTc Prolongation in Schizophrenia Patients Receiving Atypical Antipsychotics

Zhang

et al. 2022

J Clin Psychopharmacol

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Purpose:The risk of sudden cardiac death in patients receiving atypical antipsychotics may be related to QTc prolongation. The aim of this study was to investigate the risk factors for QTc prolongation to prevent QTc prolongation and guide clinical practice.Methods: All electrocardiogram recordings of 913 schizophrenia patients who were receiving atypical antipsychotics were reviewed for prolonged QTc and associated conditions. Binary logistic regression analysis was used to investigate risk factors for QTc prolongation.Results: Logistic regression analysis demonstrated that sex (odds ratio [OR], 0.386; P = 0.010), age (OR, 1.047; P = 0.000), high-density lipoprotein (OR, 0.257; P = 0.014), and antipsychotics dose (OR, 1.040; P = 0.036) were significantly associated with QTc prolongation. Conclusions:In patients with male sex, elder age, low high-density lipoprotein, or large antipsychotics dose, QTc should be monitored more frequently.

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“…In patients admitted for sertraline overdose (>200 mg), incidence of QTc interval >500 ms was 6% (6/103); incidence of QTc interval greater than 440 ms was 40% (41/103) . Incidence of maximum QTcB interval prolongation (males, QTcB >450 ms; females, QTcB >460 ms) was 7.9% (3/38) in an analysis of recordings from the Electrocardiogram Vigilance With Electronic Data Warehouse database in which dosing and concomitant medications were unknown . A case study describing a patient admitted to intensive care after a multiple‐drug overdose including 2250 mg of sertraline, 200 mg of diazepam, and 400 mg of temazepam reported an increase in QTc from 370 milliseconds at admission to 525 milliseconds 1 day later .…”

Section: Discussionmentioning

confidence: 99%

“…Although not a direct relationship, reduction of delayed rectifier potassium/hERG current is considered a surrogate marker of delayed cardiac repolarization . No significant effect of sertraline on QTc was observed in a population‐based cohort study comparing SSRI‐treated adults with untreated individuals or in either of 2 retrospective analyses of electrocardiogram (ECG) records . Nonetheless, pharmacovigilance assessments indicate that QTc prolongation may occur after ingestion of suprathreshold sertraline doses …”

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confidence: 99%

“…17 No significant effect of sertraline on QTc was observed in a population-based cohort study comparing SSRI-treated adults with untreated individuals or in either of 2 retrospective analyses of electrocardiogram (ECG) records. [18][19][20] Nonetheless, pharmacovigilance assessments indicate that QTc prolongation may occur after ingestion of suprathreshold sertraline doses. 21 Although no clinically significant effects of sertraline on QTc prolongation have been identified to date, no thorough QTc (TQTc) study for sertraline has been reported.…”

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A Thorough QT Study to Evaluate the Effects of a Supratherapeutic Dose of Sertraline on Cardiac Repolarization in Healthy Subjects

Abbas

Riley

LaBadie

et al. 2019

Clinical Pharm in Drug Dev

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The effect of steady‐state supratherapeutic sertraline (Zoloft) on QT interval was assessed in a single‐center, randomized, 3‐way crossover, double‐blind, placebo‐ and moxifloxacin‐controlled thorough QT study. Healthy adults received sertraline 400 mg/day, moxifloxacin 400 mg, and placebo, with a washout period (≥14 days) between treatments. A 12‐lead electrocardiogram was recorded in triplicate before dosing and at selected time points up to 72 hours after dosing. Analysis of covariance using a mixed‐effect model with sequence, period, treatment, time, and treatment‐by‐time interaction as fixed effects; subject within sequence as a random effect; and baseline QT corrected for heart rate using Fridericia formula (QTcF) as a covariate was conducted. A 90% confidence interval for the least squares (LS) mean difference in QTcF between active treatment and placebo was computed for each postdose time point. Exposure‐response was assessed using linear mixed‐effect modeling. Fifty‐four subjects were enrolled. Over 24 hours after dosing, the LS mean difference in QTcF for sertraline versus placebo ranged from 5.597 milliseconds to 9.651 milliseconds. The upper bound of the 90% confidence interval for the LS mean difference exceeded a predefined 10‐millisecond significance threshold at the 4‐hour postdose time point only (LS mean, 9.651 milliseconds [90% confidence interval, 7.635‐11.666]). In the exposure‐response analysis, QTcF values increased significantly with increasing sertraline concentration (slope = 0.036 milliseconds/ng/mL; P < .0001). Predicted change from baseline in QTcF at therapeutic maximum plasma sertraline concentration was 3.57 milliseconds. This thorough QTc study demonstrated a positive signal for QTc prolongation for sertraline at the steady‐state 400‐mg/day dose.

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An analysis of QTc prolongation with atypical antipsychotic medications and selective serotonin reuptake inhibitors using a large ECG record database

Abstract: This study suggests that atypical antipsychotic drugs and SSRIs are less likely to be associated with QTc prolongation in clinical settings. In addition, age showed a significant association with the QTc interval. Further studies with well-characterized cohorts are warranted.

Cited by 8 publications

References 35 publications

ECG-ViEW II, a freely accessible electrocardiogram database

ECG-ViEW II, a freely accessible electrocardiogram database

A Real-World Study of Risk Factors for QTc Prolongation in Schizophrenia Patients Receiving Atypical Antipsychotics

A Thorough QT Study to Evaluate the Effects of a Supratherapeutic Dose of Sertraline on Cardiac Repolarization in Healthy Subjects

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