Systematic Review and Meta-Analysis: Early Treatment Responses of Selective Serotonin Reuptake Inhibitors in Pediatric Major Depressive Disorder

OBJECTIVE:Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for pediatric major depressive disorder (MDD). We conducted a meta-analysis to examine the following: the time-course of response to SSRIs in pediatric depression; whether higher doses of SSRIs are associated with an improved response in pediatric depression; differences in efficacy between SSRI agents; and whether the time-course and magnitude of response to SSRIs is different in pediatric and adult patients with MDD. METHOD:We searched PubMed and CENTRAL for randomized controlled trials comparing SSRIs to placebo for the treatment of pediatric MDD. We extracted weekly symptom data from trials to characterize the trajectory of pharmacological response to SSRIs. Pooled estimates of treatment effect were calculated based on standardized mean differences between treatment and placebo groups. RESULTS:The meta-analysis included 13 pediatric MDD trials with a total of 3,004 patients. A logarithmic model indicating that the greatest benefits of SSRIs occurred early in treatment best fit the longitudinal data (log[week] = 0.10, 95% CI = 0.06-0.15, p < .0001). There were no significant differences based on maximum SSRI dose or between particular SSRI agents. SSRIs were demonstrated to have a smaller benefit in pediatric compared to adult MDD. CONCLUSION:Treatment gains in pediatric MDD are greatest early in treatment and are, on average, minimal after 4 weeks of SSRI pharmacotherapy in pediatric MDD. Further research is needed using individual patient data to examine the power of early SSRI response (e.g., 2-4 weeks) to predict outcomes in short-term pharmacological trials.