Antidepressant Effect Sizes Modest for Pediatric Major Depressive Disorder

Antidepressants demonstrated just a small effect size for pediatric major depressive disorder in industry-funded trials, according to a systematic review and meta-analysis published in the Journal of Affective Disorders.

Researchers at Massachusetts General Hospital and Harvard Medical School in Boston analyzed 19 double-blind, randomized clinical trials investigating antidepressants in children and adolescents with major depressive disorder in an attempt to better understand how study design and placebo response might contribute to findings.

Thirty-four antidepressant-placebo comparisons, spanning a total 6161 children and adolescents, were included. Antidepressants in the studies were agomelatine, duloxetine, citalopram, escitalopram, fluoxetine, levomilnacipran, paroxetine, selegiline, sertraline, venlafaxine, vilazodone, and vortioxetine.

The standardized mean difference (SMD) in change in Children's Depression Rating Scale-Revised (CDRS-R) scores was 0.12 with antidepressants, according to the study. Researchers characterized the effect size as “very small” and less than what has been reported in studies of adults with major depressive disorder. Compared with -19.99 points among children who received placebo, the mean change in CDRS-R score was -22.45 points among pediatric participants who received antidepressants, Psychiatry Advisor reported.

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Limiting the meta-analysis to studies with a low mean placebo response increased the SMD to 0.19. When studies with at least 50% chance of receiving placebo were included in the meta-analysis, the SMD further rose to 0.22.

By antidepressant type, fluoxetine showed the highest SMD (0.21), followed by selective serotonin reuptake inhibitors (SSRIs; 0.20) and non-fluoxetine SSRIs (0.20), according to Psychiatry Advisor coverage. Non-SSRI treatments demonstrated the lowest SMD: 0.07.

Many of the trials comprised older children and younger adolescents and, as a result, findings from the meta-analysis may not reflect antidepressant efficacy in older adolescents, researchers noted.

“The modest SMD identified in this analysis may reflect study design factors and the application of antidepressants developed for adults to pediatric patients,” they concluded. “Given the urgent clinical need for more pediatric major depressive disorder treatments, the influence of placebo response and the need for drug development tailored to this population should be considered in … trial design.”

--Jolynn Tumolo



Feeney A, Hock RS, Fava M, Hernández Ortiz JM, Iovieno N, Papakostas GI. Antidepressants in children and adolescents with major depressive disorder and the influence of placebo response: a meta-analysis. J Affect Disord. 2022;305:55-64. doi: 10.1016/j.jad.2022.02.074

Nye J. Antidepressants have small effect sizes for the treatment of major depressive disorder among children. Psychiatry Advisor. March 23, 2022. Accessed May 13, 2022.

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