New-generation antidepressants, suicide and depressed adolescents : how should clinicians respond to changing evidence?

The purpose of the present paper was to identify, from the voluminous literature on efficacy and safety in new-generation antidepressants (NGAs) with depressed children and adolescents, practical clinical strategies for acute phase treatment. To this end a pragmatic survey of studies and reviews was undertaken. Meta-analyses of randomized controlled trials of NGAs in depressed children and adolescents have noted a comparative lack of efficacy, and a weak but statistically significant increased risk of self-harm and suicidal thoughts. But NGA prescription rates and youth suicide rates are generally inversely related, and ensuing 'black box' warnings about NGAs, by deterring NGA prescribing, have possibly contributed to rising youth suicide rates. In moderate-severe depression, benefits for fluoxetine and possibly other NGAs demonstrably outweigh risks. NGAs are not present in adolescents who die by suicide. Concern about NGA risks must be balanced against risks of non-treatment. While mild depression entails regular review, psychoeducation, self-care strategies and psychological interventions, NGAs should be administered concurrently with psychological treatments if depression is moderate- to severe, or if mild depression persists. Patients should be warned about off-label status of NGAs in depression, serious side-effects such as 'activation', suicidality, emotional blunting and manic switches, the need for adherence and avoiding abrupt discontinuation. They should be monitored early and regularly. Better evidence is required regarding psychological treatments, clinical course, and clinical practice trends. In moderate-severe depression the risk of suicide if NGAs are not used may outweigh any risk of self-harm associated with them.