The main finding is that there were no deaths. Two cases of serious cardiotoxicity were reported,

but one was associated with concomitant chlorpromazine and the other with thioridazine. In another large case series of 235 patients admitted to the Edinburgh Royal Infirmary following venlafaxine overdose, no deaths were reported, although a dose-dependent relationship between venlafaxine ingestion, Inhibitors,research,lifescience,medical tachycardia and corrected QT interval (QTc) prolongation was found and arrhythmias were documented in three patients [Howell et al. 2007]. Prolongation of the QT interval is associated with an increased risk of the potentially lethal cardiac arrhythmia, STA-4783 mw torsades de pointes, a risk that increases with the use of QT prolonging drugs [Anderson et al. 2002]. No cases of torsades Inhibitors,research,lifescience,medical de pointes were reported in this study and to the authors’ knowledge no cases have been published in the literature, although two cases have been reported on the ADROIT database [MHRA, 2012] neither of which were fatal. The analysis by Howell and colleagues used Bazett’s formula to calculate the QTc for heart rate. This is reported to overcorrect at higher heart rates [Desai et al. 2003] and, as venlafaxine is associated with tachycardia in overdose,

this may have influenced the findings in this study. Further case series of 96 cases of venlafaxine Inhibitors,research,lifescience,medical overdose [Kelly et al. 2004]and 51 cases of venlafaxine overdose [Whyte et al. 2003] also did not report any deaths on venlafaxine. The data reported by Whyte and colleagues have now been expanded, and venlafaxine overdoses for which ECGs Inhibitors,research,lifescience,medical were recorded were available for 273 patients on 369 occasions [Isbister, 2009]. No deaths were reported and venlafaxine was only found to cause minor abnormalities in the QT and QRS interval, unlikely to be associated with major arrhythmias except possibly with large doses. There are some data associating large

overdoses of venlafaxine with cardiotoxicity [Bosse et al. 2008; Hojer et al. 2008]. In a retrospective Inhibitors,research,lifescience,medical cohort study of 36 cases of venlafaxine self-poisoning and 44 randomly selected SSRI self-poisoning cases admitted to an emergency department in Australia, one death was reported in the venlafaxine group [Chan et al. 2010]. This patient had ingested 12,600 mg of venlafaxine XR with propanolol, else alcohol and amphetamine. No deaths were reported in the SSRI group. No clinically relevant changes in QT interval were noted. In this study venlafaxine was found to be prescribed preferentially in patients at a higher risk of serious suicide attempt. Duloxetine There are far fewer published cases on duloxetine overdoses. Two individual reports of overdoses on duloxetine have been reported [Kruithof et al. 2011; Menchetti et al. 2009]. Neither case was fatal.