QT interval prolongation associated with venlafaxine administration

Letsas, Κonstantinos P.; Korantzopoulos, Panagiotis; Pappas, Loucas; Evangelou, Dimitrios; Efremidis, Michalis; Kardaras, Fotios

doi:10.1016/j.ijcard.2005.03.065

Cited by 47 publications

(34 citation statements)

References 10 publications

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“…Data were available for 858 ECG recordings that were taken from 541 patients with median (IQR) age 34 years (25-42 years), including 161 men (29.8%).The median stated dose ingested, as a multiple of the defined daily dose was similar between groups: citalopram 16 (10-30), mirtazapine 15 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), and venlafaxine 15 (9-28). None of the patients studied developed torsade de pointes or other significant arrhythmia.…”

Section: Resultsmentioning

confidence: 99%

“…A relationship exists between citalopram dose and the risk of QT prolongation and torsades de pointes is a recognized complication of citalopram toxicity [15][16][17].Administration of oral activated charcoal after overdose can prevent QT prolongation and reduce arrhythmia risk [18]. By contrast, venlafaxine causes QT prolongation and tachyarrhythmia but neither mirtazapine nor venlafaxine overdose have been reported to cause torsades des pointes [11,19]. The scatterplots show different heart rate-QT relationships between the selected agents, and the citalopram group had a more heart rate values in the range typically associated with torsades de pointes, namely <90 beats min -1 .…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of a QT nomogram for risk assessment after antidepressant overdose

Waring

Graham

Gray

et al. 2010

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Overdose with citalopram is associated with QT prolongation and torsades de pointes, whereas this arrhythmia has not been reported after venlafaxine or mirtazapine overdose.• Uncertainty exists concerning the best means of identifying poisoned patients at greatest risk of arrhythmia, and a nomogram comparing QT and heart rate has recently been proposed based on published cases of torsades de pointes.• Few data are available concerning the performance of the nomogram in patients that present to hospital after antidepressant overdose. WHAT THIS STUDY ADDS• After antidepressant overdose patients had a broad range of heart rate and QT values, which were below the nomogram in 98% of cases (95% confidence interval 96, 99%).• Citalopram overdose was associated with a higher proportion of patients with QT values above the nomogram than venlafaxine and mirtazapine overdose, especially in those who had low heart rates.• The nomogram allowed discrimination between the different antidepressant agents and may have a role in predicting arrhythmia in clinical practice. AIMSA QT-heart rate nomogram has recently been proposed as a means of identifying patients at risk of torsades de pointes after antidepressant overdose, based on published cases of drug-induced torsades de pointes. The present study sought to examine the performance of the nomogram in patients who ingest an antidepressant overdose but do not develop arrhythmia. METHODSA retrospective case control study of patients presenting to hospital after overdose of citalopram, mirtazapine and venlafaxine was carried out. The primary outcome variable was QT higher than the nomogram, and was compared with occurrence of QTc (QT corrected by Bazett's formula) greater than Ն440 ms and QTc Ն500 ms, with comparison between drugs. Data are expressed as proportions in each group with 95% confidence intervals. RESULTSThere were 858 electrocardiograms from 541 patients. QT was higher than the nomogram in 2.4% (1.4, 4.1%), whereas QTc was Ն440 ms in 23.1% (95% CI 19.8, 26.8%), and QTc was Ն500 ms in 1.1% (0.5, 2.5%). Citalopram overdose was more likely to be associated with QT higher than the nomogram compared with the other agents (difference 7.0%, 95% CI 2.9, 11.9%, P = 0.001) and more likely to be associated with QTc Ն440 ms (difference = 11.0%, 95% CI 2.6, 19.0%, P = 0.013). CONCLUSIONSThe QT nomogram was associated with a lower false positive rate than widely accepted QTc criteria, and allowed detection of different effects of individual drugs. The nomogram offers potential advantages over QTc criteria and merits further investigation in a clinical setting.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of a QT nomogram for risk assessment after antidepressant overdose

Waring

Graham

Gray

et al. 2010

Brit J Clinical Pharma

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“…We have previously reported on the role of citalopram in causing QTc prolongation, TdP, widening of the QRS complex, and junctional rhythm with sinus arrest and/or AV dissociation. 6 Sporadic case reports implicate venlafaxine, 7 escitalopram, 8 and fluvoxamine 9 as QT-prolonging agents as well. Among the tricyclic antidepressants, amitriptyline is one of the most commonly associated with TdP.…”

Section: Drug-induced Long Qt Syndromementioning

confidence: 99%

Acquired Long QT Interval: A Case Series of Multifactorial QT Prolongation

Digby

Pérez‐Riera

Barros

et al. 2011

Clinical Cardiology

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Background: Acquired long QT (LQT) interval is thought to be a consequence of drug therapy and electrolyte disturbances. Hypothesis: We characterize the potential effects of polypharmacy in a case series of acquired LQT and torsades de pointes (TdP) in order to determine whether multiple risk factors play a role in the development of LQT. Methods: The case series consisted of 11 patients presenting to 4 tertiary care hospitals with LQT and ≥2 risk factors for developing LQT. Clinical characteristics, medications, electrolyte disturbances, and course in hospital were analyzed. Results: Mean age was 49.1 ± 5.8 years. Eight patients were female. Four had hypertension, 1 had a history of dilated cardiomyopathy, and 1 patient demonstrated complete atrioventricular block. Average QTc interval at presentation was 633.8 ± 29.2 ms. Nine patients developed TdP. In 3, LQT was not initially detected and amiodarone was administered, followed by development of TdP. Patients were taking an average of 2.8 ± 0.3 QT-prolonging medications-an antidepressant in 6 cases and a diuretic in 8 cases. All patients had an electrolyte abnormality; 8 patients presented with severe hypokalemia (<3.0 mmol/L). Average serum potassium and magnesium were 2.82 ± 0.10 mmol/L and 0.75 ± 0.03 mmol/L, respectively. There were no deaths. Conclusions: This case series highlights the risks of polypharmacy in the development of LQT and TdP. It illustrates the importance of early detection of LQT in patients with multiple risk factors in ensuring appropriate treatment.

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“…However, a cardiotoxic effect cannot be excluded -specifically when an overdose has been administered [31] .…”

Section: Q-t Prolongation and Cardiotoxic Effects During Ad Therapymentioning

confidence: 99%

“…In the reports by Service and Waring [35] and Letsas et al [31] , respectively, cardiotoxic adverse effects of overdoses of trazodone (1.5 g) and venlafaxine (150 mg) were described. Both drugs are generally considered safe; this does not, however, prevent Q-T prolongation due to pronounced overdosing.…”

Section: Q-t Prolongation and Cardiotoxic Effects During Ad Therapymentioning

confidence: 99%

Antidepressants: Clinically Relevant Drug Interactions to Be Considered

Schellander

Donnerer²

2010

Pharmacology

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Drug interactions in clinical practice are common and have developed into an increasing challenge for the medical profession. Specifically antidepressant drugs (ADs), which are among the 5 most frequently prescribed drugs, are predestined for adverse drug interactions because of their multiple mechanisms of action and/or their influence on drug-metabolizing cytochrome P450 (CYP) enzymes. Although selective serotonin reuptake inhibitors (SSRIs) and other new-generation ADs have an overall improved safety profile, their potential for drug interactions is to be considered. A review of the current literature has been performed, and selected examples of clinically relevant interactions with ADs have been chosen. With regard to pharmacodynamic interactions, the serotonin syndrome, the risk of bleeding under SSRI therapy, and the corrected Q–T interval prolongation are discussed in this review. The inhibitory effects of new-generation ADs on CYP enzymes show great variability and might be relevant for prescription recommendations in elderly patients and in patients with polypharmacy. The CYP-enzyme-inducing effect of St. John’s wort, a popular over-the-counter herbal drug, may lead to decreased plasma levels of CYP substrates. When comparing prescription data and observed adverse drug events, there is fortunately a safety gap between the number of potential drug-drug interactions and the number of clinically observed side effects due to drug-drug interactions.

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QT interval prolongation associated with venlafaxine administration

Cited by 47 publications

References 10 publications

Evaluation of a QT nomogram for risk assessment after antidepressant overdose

Evaluation of a QT nomogram for risk assessment after antidepressant overdose

Acquired Long QT Interval: A Case Series of Multifactorial QT Prolongation

Antidepressants: Clinically Relevant Drug Interactions to Be Considered

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