A review of the suitability of duloxetine and venlafaxine for use in patients with depression in primary care with a focus on cardiovascular safety, suicide and mortality due to antidepressant overdose.

Depression and anxiety disorders are among the most common disorders treated by general practitioners (GPs) in the UK. Since both disorders are associated with a significantly increased risk of suicide, including with antidepressant overdose, the safety of antidepressants in overdose is of paramount importance. Numerous updates relating to antidepressant safety have been issued by regulators in the UK which may have eroded GP confidence in antidepressants. Venlafaxine, a serotonin nor adrenaline reuptake inhibitor (SNRI) had primary care prescribing restrictions placed on it in 2004 due to concerns about cardiotoxicity and mortality in overdose. Although a review of the evidence led to a reversal of the majority of restrictions in 2006, evidence suggests GPs may still be cautious in their prescribing of venlafaxine and possibly other SNRI antidepressants for patients with depression and anxiety disorders. This paper reviews the evidence pertaining to the safety of SNRI antidepressants from a perspective of cardiovascular safety and overdose. The currently available evidence suggests a marginally higher toxicity of venlafaxine in overdose compared with another SNRI duloxetine and the selective serotonin reuptake inhibitors (SSRIs), although this may be related to differential patterns of prescribing in high-risk patients. Based on this review SNRIs have a positive risk benefit profile in the treatment of depression and generalized anxiety disorder in primary care, especially as second-line agents to SSRIs.