What is already known about this subject • Recent concerns about lack of cardiovascular safety have led to restrictions in the use of venlafaxine in the UK. • Venlafaxine may predispose to arrhythmia in high‐risk individuals. What this study adds • Venlafaxine ingestion gave rise to sympathomimetic cardiovascular features and QTc prolongation in previously healthy young adults. • These findings suggest plausible mechanisms by which venlafaxine might predispose to arrhythmia, and require further consideration. Aims Venlafaxine may increase the risk of arrhythmia in certain patients. We sought to characterize the cardiovascular effects of venlafaxine overdose in adults. Methods A retrospective casenote review of patients admitted to the Royal Infirmary of Edinburgh between January 2000 and June 2006. Haemodynamic and electrocardiographic data were examined in the whole group and a subset that ingested venlafaxine alone. Results Two hundred and thirty‐five patients (65 men) with median (interquartile range) age 34 years (27–43 years) had ingested venlafaxine 1500 mg (919–2800 mg). Tachycardia (40.0%), high blood pressure (28.4%) and mydriasis (36.6%) were common. Corrected QT >450 ms occurred in seven men (11.1%) and 17 women (10.5%) and transient arrhythmia in three patients. There was a positive correlation between stated quantity of venlafaxine ingested and heart rate [ρ = 0.195, 95% confidence interval (CI) 0.054, 0.328] and QTc (ρ = 0.314, 95% CI 0.089, 0.509). Conclusions Venlafaxine overdose is associated with sympathomimetic cardiovascular effects and prolonged QTc, irrespective of coingested drugs. These mechanisms might pose an increased risk of arrhythmia and require further exploration.

METHODOLOGYThis guideline was compiled according to the BSH process at http://www.b-s-h.org.uk/guidelines/. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate the levels of evidence and to assess the strength of recommendations. The GRADE criteria can be found at http://www.gradeworkinggroup .org.This guideline represents the minimum requirements for the safe administration of blood component transfusions. These are intended to provide the foundations for organisations to build on when developing their own local policies and guidelines. However, it should be recognised that the more complex the procedures are, the more open to error they become.

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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.