2007]. Once these confounders had been adjusted for, the hazard ratios were substantially reduced [from 2.85, 95% confidence interval (CI) 1.37–5.94 to 1.63, 95% CI 0.74–3.59 for venlafaxine versus fluoxetine]. However one can only adjust for those factors that can be measured and major risk factors such as hopelessness, impulsivity,

abuse, unemployment and social isolation were not measured and thus not adjusted for, meaning further confounders may still have been present in the data. Further evidence for the channelling of venlafaxine use towards patients Inhibitors,research,lifescience,medical with a higher risk of suicidal behaviour has been published using data from three primary care trusts (PCTs) in the UK [Bergen et al. 2010] and in an Australian study [Chan et al. 2010]. The MHRA has also concluded that the increased FTI is at Inhibitors,research,lifescience,medical least partially contributable to these patient factors [MHRA, 2006]. Drug factors Drug factors can be divided into two main considerations: those involving drug-induced emergence of suicidal thoughts and behaviours, and the toxicity of individual drugs. Emergence of suicidal thoughts There is evidence of a small increase in suicidal behaviour in the first month after starting an Inhibitors,research,lifescience,medical antidepressant [Jick et al. 2004]. A recent

review for the World Psychiatric Association has concluded Inhibitors,research,lifescience,medical that antidepressants carry a small risk of inducing suicidal ideation and DNA Damage inhibitor behaviours in people under 25 years, although this risk reduces in those aged between 30 and 40 years [Moller et al. 2008]. There are data available on the emergence of suicidal thoughts and behaviours specific to duloxetine and venlafaxine use. Acharya and colleagues Inhibitors,research,lifescience,medical compared incidence of suicide-related events with

duloxetine versus placebo in controlled trials, using Mantel–Haenszel incidence difference methods [Acharya et al. 2006]. They found no evidence of increased risks of suicidal behaviours or ideations during treatment with duloxetine compared with placebo in patients with major depressive Terminal deoxynucleotidyl transferase disorder. Enstuah and colleagues found in an 8-week study that fewer patients on venlafaxine than on SSRIs developed emergent suicidal thoughts, as shown in Figure 2 [Enstuah et al. 2001]. In a recent person-level analysis of all sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine, both treatments were found to decrease suicidal thoughts and behaviours compared with placebo in adult patients and older patients, although no difference was found in young patients [Gibbons et al. 2012]. This was mediated through decreases in depressive symptoms through treatment.