Evaluation of a QT nomogram for risk assessment after antidepressant overdose

Abstract

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.

Development and validation of a risk-prediction nomogram for in-hospital mortality in adults poisoned with drugs and nonpharmaceutical agents

“…[4] They reduce statistical predictive models into a single numerical estimate, tailored to the profile of an individual patient, indicating the probability of an event, such as death or recurrence. [1] In clinical toxicology, several nomograms have been developed, including the Done nomogram, indicating the severity of toxicity based on 6-hour levels of non-enteric-coated aspirin, [5] currently with limited clinical use; the Rumack–Matthew nomogram, for antidote therapy decision in acetaminophen overdose [6] ; the QT nomogram, predictive for arrhythmogenic risk of drug-induced QT prolongation, [7] particularly in antipsychotic, [8] and antidepressant overdoses [9] ; and graphical nomograms predicting drug concentration. [10] To be relevant for clinical practice, the accuracy of a risk assessment tool should be greater than that of a practitioner's assessment in the emergency department (ED).…”

Review of treatment for late-life depression

“…Although citalopram was previously recommended for use in those with cardiovascular disease, recent data have highlighted the risk of prolonged QT interval with the drug, and the maximum recommended dose for older adults has now been reduced (Waring 2010;Fayssoil 2011;Howland 2011). Citalopram should not be prescribed in conjunction with other agents that prolong the QT interval, such as antipsychotics and certain antibiotics (e.g.…”

Propofol-associated QTc prolongation

“…The retrospective, nonrandomized nature of this study precludes making statements regarding causation between propofol administration and QTc prolongation given that no control group could be evaluated. The measurement of the QTc interval is potentially unreliable depending on the techniques used to calculate its length or with heart rate extremes during automated ECG assessments [Isbister and Page, 2013;Waring et al 2010]. The manual interpretation by OUMC cardiologists mitigated variability in QTc measurement and its influence as a confounder in this evaluation.…”