Citalopram-induced long QT syndrome and torsade de pointes: Role for concomitant therapy and disease

Gregorio, Cesare de; Morabito, Gaetano; Cerrito, Marco; Dattilo, Giuseppe; Oreto, Giuseppe

doi:10.1016/j.ijcard.2009.05.060

Cited by 29 publications

(16 citation statements)

References 8 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].…”

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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“…De Gregorio et al [33] reported about a 48-year-old woman who was admitted to the hospital because of syncope. She suffered from major depression and hypertension and was taking 40 mg citalopram and 25 mg furosemide daily.…”

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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“…Several non-antiarrhythmic drugs [3][4][5] have been shown to prolong cardiac repolarization predisposing to torsade de pointes ventricular tachycardia. Blockade of the delayed rectifier (repolarising) potassium current and drug interactions with inhibitors of the cytochromes P450 (CYP)-mediated metabolism are the most common underlying mechanisms [6,7].…”

mentioning

confidence: 99%

“…Data for infant mortality in 1935, and for mortality from stomach cancer (ICD-9: 29), stroke (ICD-9: 430-438), lung cancer (ICD-9: 162), ischemic heart disease (ICD-9: 410-414) and all-causes of death among adults aged 60-84 years in 1995 were obtained from Japan national vital statistics [4]. Age-adjusted mortality rates were estimated using direct method with the world population as the standard.…”

mentioning

confidence: 99%

Torsade de pointes, QT interval prolongation and renal disease

Patanè¹

2011

International Journal of Cardiology

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Citalopram-induced long QT syndrome and torsade de pointes: Role for concomitant therapy and disease

Cited by 29 publications

References 8 publications

Evaluation of a QT nomogram for risk assessment after antidepressant overdose

Evaluation of a QT nomogram for risk assessment after antidepressant overdose

Antidepressants: Clinically Relevant Drug Interactions to Be Considered

Torsade de pointes, QT interval prolongation and renal disease

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