Pharmacological treatment of children and adolescents with depression

ABSTRACT

Introduction: Despite an increasing number of studies, there is debate whether antidepressants have a favorable benefit/risk balance in depressed youth.

Areas covered: A systematic search identified 23 systematic reviews and meta-analyses published between 2010–2016. More than 30 controlled clinical trials were conducted in adolescents, but only a few in pre-pubertal patients. About one-third of the trials were severely statistically underpowered. Most studies failed to detect differences from placebo, but a few found fluoxetine effective. Although no suicide occurred in these studies, antidepressants increased suicidality risk (including suicidal ideation and behavior) versus placebo (OR = 2.39). Only two placebo-controlled trials with acceptable statistical power were publicly funded: both showed efficacy of fluoxetine, and one found a higher incidence of suicidality (OR = 3.7, 95% C.I. 1.00–13.7).

Expert opinion: In youth, antidepressants have, on average, a small therapeutic effect. The high placebo response is exacerbated by the large number of sites in many industry-funded studies. There is evidence that fluoxetine leads to greater and faster improvement than placebo or psychotherapy in adolescents. Considering both the high response to non-specific interventions and safety concerns, antidepressants should be used cautiously in youth, and limited to patients with moderate-to-severe depression for whom psychosocial interventions are either ineffective or not feasible.

KEYWORDS:

• Antidepressants
• children and adolescents
• depressive disorder
• efficacy
• safety

Article highlights

• Most placebo-controlled clinical trials have high placebo response and failed to find a statistically significant difference in efficacy.

• Many clinical trials have important methodological limitations, in particular a high number of clinical sites and major heterogeneity of clinical settings, which likely contributed to the high placebo response.

• There is a role for the use of SSRI antidepressants in the treatment of adolescents with moderate or severe major depressive disorder that does not respond to initial psychosocial intervention.

• There is well-documented evidence of the efficacy of fluoxetine in adolescent depression, with a medium effect size. Less consistently documented evidence also exists for the efficacy of other selective serotonin re-uptake inhibitors (SSRI), such as escitalopram, citalopram, and sertraline.

• The mechanisms responsible for the increased risk of suicidal events with antidepressants in young people remain obscure.

• Research is needed to identify the specific groups of youth for whom antidepressants are beneficial without causing major adverse effects.

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Acknowledgements

The opinions and assertions contained in this article are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of Health and Human Services, the National Institutes of Health, or the National Institute of Mental Health.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This article was written as part of the authors’ employment at the National Institutes of Health, U.S. Department of Health and Human Services.