One important group of antidepressants for which there have been safety concerns in the past is the SNRIs. There is evidence to suggest that the confidence of GPs in the safety of the SNRI venlafaxine may have been eroded following the MHRA urgent safety restriction (USR) issued in 2004 [MHRA, 2004] after which prescribing rates diminished over the next

year [McAllister-Williams et al. 2006]. Venlafaxine has been licensed for the treatment of depression in the UK since Inhibitors,research,lifescience,medical 1994 and had been increasingly prescribed by GPs and specialists as a second-line treatment for depression. The USR related to potential toxicity in www.selleckchem.com/products/wp1066.html overdose and it restricted the initiation of venlafaxine to mental health specialists and gave new contraindications Inhibitors,research,lifescience,medical in patients with heart disease. In 2006, after a reexamination of the safety evidence and taking into account new epidemiological data, the MHRA released updated guidance on the prescribing of venlafaxine [MHRA, 2006]. This new guidance removed the recommendation for specialist initiation of venlafaxine along with some of the contraindications, and requirement for baseline electrocardiogram (ECG) monitoring, again allowing its initiation by GPs in primary care. Despite this change of guidance in 2006, prescribing of venlafaxine in primary care has since remained static [Ilyas and Moncrieff, 2012], and against Inhibitors,research,lifescience,medical a background of increasing antidepressant use, it may

be conjectured that GPs are still wary of prescribing venlafaxine in primary care. In 2005 a second SNRI, duloxetine, was licensed for the treatment of depression. We speculate that many GPs may take the view that, as an SNRI, this may also carry a higher risk of cardiotoxicity or other toxicity than other antidepressants. This paper aims to review the data examining mortality Inhibitors,research,lifescience,medical associated with overdose of venlafaxine and duloxetine, Inhibitors,research,lifescience,medical including the data examining suicidality and cardiovascular safety. Based on this evidence, recommendations can then be made as to their suitability for use in primary care from a perspective of these major safety issues. The review will take the

following structure: (1) Mortality due to overdose of venlafaxine and duloxetine. The evidence of how these data are synthesized and analyzed using the fatal through toxicity index (FTI) will be reviewed. This will be followed by a review of deaths from overdose using case series which are easy to understand and give further information on the safety of antidepressants. (2) A brief review of cardiovascular safety of the SNRIs will be presented. Mortality due to overdose of venlafaxine and duloxetine Measuring overdose mortality for antidepressants is relatively straightforward in the UK, but interpreting the data is difficult due to a number of factors. The simplest way of assessing overdose mortality is to count the deaths of those who have overdosed on antidepressants [available from the Office of National Statistics (ONS) who are informed via the coroners].