Antidepressants Have Modest Effect on Major Depressive Disorder Among Children

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A systematic review and meta-analysis found that antidepressants had only a modest effect among pediatric patients with major depressive disorder (MDD). These findings were published in the Journal of Affective Disorders.

Investigators at Massachusetts General Hospital and Harvard Medical School searched publication databases through January 2021 for placebo-controlled studies of treatment for MDD among pediatric patients. A total of 15 published and 4 unpublished studies were included in this analysis and a total of 34 drug-placebo comparisons were evaluated.

The patient population comprised 6,161 patients, aged mean 13.15 (range, 7-17) years, and baseline Children’s Depression Rating Scale-Revised (CDRS-R) score was 58.73 (standard deviation [SD], 2.80) points. The patients received antidepressants (n=3,844) or placebo (n=2,317) for 8 to 12 weeks. The antidepressants included agomelatine, duloxetine, citalopram, escitalopram, fluoxetine, levomilnacipran, paroxetine, selegiline, sertraline, venlafaxine, vilazodone, and vortioxetine.

Antidepressants had a modest effect overall (standardized mean difference [SMD], 0.12; 95% CI, 0.08-0.17; P <.001; τ², 0.0027) with a mean change in CDRS-R score of -22.45 (SD, 2.42) points among antidepressant recipients and -19.99 (SD, 4.07) points among placebo recipients.

Stratified by antidepressant, the effects were higher for fluoxetine (SMD, 0.21; P =.001; τ², 0.0178), selective serotonin reuptake inhibitors (SSRIs; SMD, 0.20; P <.001; τ², 0.0105), and nonfluoxetine SSRIs (SMD, 0.20; P =.001; t², 0.0052) than studies with non-SSRI treatments (SMD, 0.07; P =.026; τ², 0.0000).

The greatest effect was observed for studies in which the placebo group had CDRS-R score changes below the median (-21.5 points) and fluoxetine was the active treatment (SMD, 0.32; P <.001; τ², 0.0185).

No significant effects were observed for baseline severity (P =.986), age (P =.884), or proportion of adolescent patients (P =.869).

This analysis may have been limited by the uniform age of study participants (13-14 years) and the results may not be generalizable to younger children or older adolescents.

“In conclusion, currently approved antidepressants for children and adolescents with MDD have small effect sizes and many antidepressant trials in this population fail. Antidepressant drug development for children and adolescents needs to be tailored, rather than simply applying adult-approved treatments to children. The influence of placebo response should be considered in pediatric MDD clinical trial design and implementation,” noted the study authors.