Commentary

Isacsson et al provide new insights into the debate about the relation between antidepressants and suicidal behaviour.¹ Based on recent evidence that some antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), possibly increase the risk of suicide² and suicide ideation³ in people with depression, worldwide regulatory authorities have issued warnings about the risk of self harm and suicidal thinking or behaviour in children, adolescents, and adults taking antidepressants.^4,6 However, the study by Isacsson appears to support the findings of studies that report increased antidepressant use to be associated with a decreased suicide rate.^7,8

Notwithstanding the importance of a precautionary attitude when dealing with crucial health policy matters such as suicide risk, substantial methodological limitations of the available evidence can be found. Deliberate self harm is usually under- or non-reported, and deaths by suicide can be difficult to identify. Observational data raise the problem of confounding by indication or other known and unknown variables. Existing randomised controlled trials are usually regulatory trials with carefully selected groups of participants rather than real-world patients, and have insufficient power to provide clear evidence on the effect of antidepressants on suicide.⁹

Although it has been suggested that the recommendations for prescribing antidepressants should be reconsidered,¹⁰ the most robust available evidence indicates that these drugs remain the mainstay for treating moderate to severe depression.¹¹ For clinicians the problem is how to balance the possible benefits and risks of treatment for each individual patient. Large long term non-commercial trials with clinically meaningful outcomes, that are intended to provide information about what may happen to real-world patients in terms of both effectiveness and safety, are urgently needed.⁹