Effect of antidepressants on functioning and quality of life outcomes in children and adolescents with major depressive disorder: a systematic review and meta-analysis

Functioning and quality of life (QOL) are typical outcomes assessed in children and adolescents with major depressive disorder (MDD); however, meta-analytical evidence remains scarce. The aim of this meta-analysis was to assess functioning and QOL antidepressant outcomes in this population. Eight electronic databases (PubMed, Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LILACS, and ProQuest Dissertation Abstracts) were searched for double-blind randomized controlled trials (RCTs) up to July 31, 2020. RCTs that compared antidepressants with placebo for treating functioning and QOL in children and adolescents with MDD were included. Primary outcomes were mean change scores of functioning and QOL scales from baseline to post-treatment. Subgroup and sensitivity analyses were conducted to examine whether results were affected by moderator variables (e.g., medication type, age, sample size, and treatment duration). From 7284 publications, we included 17 RCTs (all 17 assessed functioning and 4 assessed QOL outcomes) including 2537 participants. Antidepressants showed significant positive effects on functioning (standardized mean difference [SMD] = 0.17, 95% confidence interval [CI] = 0.09-0.25, p < 0.0001) but not on QOL (SMD = 0.11, 95% CI = -0.02 to 0.24, p = 0.093), with no significant heterogeneity. The subgroup analysis showed that second-generation antidepressants (especially fluoxetine, escitalopram, and nefazodone), but not first-generation antidepressants, led to significant improvements in functioning. Antidepressants (especially second generation) improve functioning but not QOL in children and adolescents with MDD. However, well-designed clinical studies using large samples are needed to confirm these findings.