There is uncertainty about the safety of selective serotonin reuptake inhibitors (SSRIs), which may cause worsening of suicidal thoughts in vulnerable people.1,2 In 2005, a systematic review of published randomized controlled trials comparing SSRIs with another active treatment or placebo found an almost 2-fold increase in the odds of fatal and nonfatal suicide attempts among those exposed to SSRIs. 3 No increase in risk was observed, however, when only fatal suicide attempts were included. Another systematic review, 4 which included both published and unpublished randomized controlled trials submitted by pharmaceutical companies to the safety review of the Medicine and Healthcare products Regulatory Agency compared the use of SSRIs and placebo in adults with depression and other clinical conditions. 4 This review showed no evidence of increased risk of completed suicide and only weak evidence of increased risk of self-harm.More recently, the US Food and Drug Administration (FDA) performed a meta-analysis of individual patient data from 372 randomized placebo-controlled trials of antidepressants with a total of nearly 100 000 patients. 5 This study reported that the incidence of reported suicidal behaviour was strongly related to age. 5 The risk associated with antidepressant use relative to placebo was increased among patients aged 25 or fewer years, and it was reduced among patients aged 65 or more years. 5 The risk among patients aged 25-64 years was neutral; however, risk was reduced when suicidal behaviour and ideation were considered together.5 Based on these findings, in May 2007 the FDA ordered that all antidepressant drugs carry an expanded black-box warning on their label that included information about increased risk of suicidal behaviour in young adults aged 18-24 years. 6,7 A controversial point of the FDA analysis is that the included trials were not primarily designed to measure suicidality (a composite outcome that includes suicide ideas, preparatory acts, suicide attempts and deaths by suicide).5 Of all suicidality events, less than 30% were serious suicide attempts or deaths. Additionally, considering that suicidality was self-reported rather than observed by others in most clinical trials, it is possible that antidepressant treatment, particularly in younger individuals, enhanced communication about suicidality, which may have allowed them to become more articulate and open about their thoughts and actions. Alternatively, antidepressant treatment might have enhanced communication about suicidality in all age groups, but increased attention to adverse effects might have led to enhanced detection of suicidality in younger individuals. 5 It is unlikely that individual randomized trials will be designed to primarily investigate the effect of antidepressant use on suicidality, and future systematic reviews of clinical trial data will not be able to overcome the limitations of the FDA analysis. Therefore, we sought to further explore the association be- We explored the association between exposure...