Newer-generation antidepressants in children and adolescents with major depressive disorder

Newer-generation antidepressants in children and adolescents with major depressive disorder

Vanessa Jordan
Clinical question

Are newer-generation antidepressants effective and safe for use in children and adolescents with diagnosed major depressive disorder?

Bottom line

There were no data to inform the comparison of greatest interest: what effect do antidepressants have on resolution of a diagnosis of major depressive disorder? Findings for secondary outcomes suggest that most newer antidepressants may be associated with small and unimportant reductions in depression symptoms compared with placebo, which raises the question of whether they should be used at all.

Depressive disorder is heterogeneous, so the effects of newer-generation antidepressants in young people may be variable.

There is evidence to support a greater range of newer-generation formulations than fluoxetine for first‐line prescribing to children, including sertraline, escitalopram and duloxetine.

It remains critical to ensure there is close monitoring of suicide‐related outcomes (combined suicidal ideation and suicide attempt) in those treated with newer-generation antidepressants, given findings that many are associated with at least slightly greater odds of these outcomes.


The trial populations were uncharacteristic of those accessing public child and adolescent mental health services, in terms of the exclusion of those with comorbid disorders and those at risk of suicide. Trials were designed to examine the short‐ term effects of antidepressant medication only; however, this does not preclude the possibility that effectiveness of treatment becomes apparent over a longer period. Finally, most trials were pharmaceutically funded.


Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and physical and mental health and wellbeing. There is an association between major depressive disorder and suicidal ideation, suicide attempts and suicide. Antidepressant medication is used in moderate to severe depression; there is now a range of newer generations of these medications.

Cochrane Systematic Review

Hetrick SE, McKenzie JE, Bailey AP, et al. New generation antidepressants for depression in children and adolescents: a network meta‐analysis. Cochrane Database Syst Rev 2021;5(5):CD013674. This review contains 26 trials with a total of 6930 participants.