Since the original safety warnings, several studies have investigated the neuropsychiatric safety of varenicline.7 8 9 10 Most of the studies were observational cohorts,7 8 9 although one study examined the risk in a meta-analysis of 17 industry sponsored trials.10 None of the studies found evidence of an increased risk of depression, suicide, or non-fatal self harm with varenicline. Two major concerns, however, have been raised about the validity of these findings. Firstly, observational studies are prone to confounding by indication.11 For example, the use of drugs for smoking cessation might seem to be associated with an increased risk of suicide because smokers themselves are at increased risk of mental illness and suicide.12 13 Secondly, there is evidence that industry sponsored trials are more likely than other trials to report outcomes that are favourable to the study sponsor.14 Though the number of prescription items of varenicline dispensed in England increased from 499 in 2006 to a peak of almost a million in 2011, there was a 25% decrease from 2011 to 2013.15 This might reflect ongoing fears among prescribers and patients regarding varenicline’s safety.
