Depression is common in young people and can contribute to a variety of negative outcomes, such as poor academic functioning, difficulties in peer and family relationships, increases in substance use, and both attempted and completed suicide. This review contained 19 trials (with a total of 3353 participants) testing the effectiveness of newer generation antidepressants (these are antidepressants developed and used since tricyclic antidepressants were developed). These include the well-known selective serotonin reuptake inhibitors that have an impact primarily on the brain chemical called serotonin, as well as several other newer classes of antidepressants now being used, which aim to target noradrenaline and dopamine as well as serotonin and include selective norepinephrine reuptake inhibitors (SNRIs), norepinephrine reuptake inhibitors (NRIs), norepinephrine dopamine reuptake inhibitors (NDRIs), norepinephrine dopamine disinhibitors (NDDIs) and tetracyclic antidepressants (TeCAs)) for the treatment of depression in children and adolescents. Based on 14 of the trials (2490 participants in total), there was evidence that those treated with an antidepressant had lower depression severity scores than those on placebo, however, the size of this difference was small. Based on 17 trials (3229 participants in total), there was evidence of an increased risk (64%) of suicide-related outcomes for those on antidepressants compared with those given placebo. Where rates of adverse events were reported, this was higher for those prescribed an antidepressant. There was no evidence that one particular type of newer generation antidepressant had a larger effect than the others when compared to placebo.
It is unclear how meaningful the results regarding the effectiveness of these medications are in terms of a young person's day-to-day functioning. Children and adolescents with other conditions (such as anxiety, substance use disorder or a conduct disorder) as well as depression, and those at risk of suicide, were often excluded from trials. However, these young people are more representative of the population who present to clinical services, therefore it is not possible to predict how they would respond to antidepressants. There was often insufficient information to judge the quality of the trials accurately. With these limitations, it is difficult to answer questions about the effectiveness and safety of antidepressants for treating depression in children and adolescents. Clinicians need to provide accurate information to children and adolescents, and their families, about the uncertainties regarding the benefits and risks of newer generation antidepressant medication as a treatment option for depression. If a decision to use medication is agreed then fluoxetine might be the medication of first choice given guideline recommendations and, if used, the risk of suicide should be assessed and monitored particularly closely.