Since the black box warning of the FDA (Food and Drug Administration) regarding an increased risk of suicidality in children and adolescents treated with antidepressants, cautious prescription of antidepressant drugs in young patients became even more important. In the light of potentially severe side effects the comparative effectiveness and harms of antidepressants should be known to clinicians to provide optimal treatment.

To compare the benefits and harms of second-generation antidepressants for the treatment of Major Depressive Disorder (MDD) in children and adolescents.

To provide an evidence base for clinicians and policymakers when making informed decisions regarding the prescription of Selective Serotonin Reuptake Inhibitors and other newer antidepressants.

We updated a comparative effectiveness report of the Oregon Drug Effectiveness Review Project searching MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts up to August 2010. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias.

We could not identify any head-to-head trials. There is insufficient evidence to compare one second-generation antidepressant to another in pediatric outpatients with MDD. Evidence from a systematic review of published and unpublished data indicates, that in children and adolescents only fluoxetine shows a good risk-benefit ratio.

To date, the evidence is insufficient to make any clear inferences about the comparative benefits and harms of second-generation antidepressants for the treatment of MDD in children. Clinicians must be aware of the small benefits and the high potential risks when prescribing antidepressant medications to children and adolescents.