Systematic Review and Meta-Analysis of Individual Participant Data: Randomized, Placebo-Controlled Trials of Selective Serotonin Reuptake Inhibitors for Pediatric Obsessive-Compulsive Disorder

Objective Selective serotonin reuptake inhibitors (SSRIs) are the first choice in pharmacotherapy for children and adolescents with obsessive-compulsive disorder (OCD). SSRI-trials for pediatric OCD have never been investigated using individual participant data (IPD), which is crucial for detecting patient-level effect modifiers. Here, we performed an IPD meta-analysis on the efficacy of SSRIs compared to placebo, and a meta-regression on baseline patient characteristics which might modify efficacy. Method We used crude participant data from short-term, randomized, placebo-controlled SSRI trials for pediatric OCD, available from the registry of the Dutch regulatory authority. We also performed a systematic literature search and approached the authors to provide IPD. We performed a one- and two-stage analysis, with change on the Children’s Yale Brown Obsessive-Compulsive Scale (CY-BOCS) as the primary outcome. We used Odds Ratio (OR) with ≥ 35% CY-BOCS-reduction as the responder outcome measure. We examined modifying effect of age, sex, weight, duration of illness, family history and baseline symptom severity. We used the Cochrane Risk of Bias 2.0 tool to examine methodological rigor, and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach in order to examine certainty of evidence. Results We obtained data from 4 studies with a total of 614 patients. Our sample represented 86% of all participants ever included in double blind placebo controlled SSRI trials for pediatric OCD. Meta-analysis showed a reduction of 3.0 CY-BOCS points compared to placebo (95% CI 2.5 – 3.5), corresponding to a small effect size (0.38 Hedges’ g). Analysis of response showed an OR of 1.89 (95% CI 1.45 – 2.45). Of all possible modifiers, severity was correlated negatively with OR for response (beta -0.92, p 0.0074). Risk of bias was generally low. All studies were performed on the North American continent with an overrepresentation of White participants. Our findings were limited by the inability to include data on additional variables such as socio-economic status and comorbidities. Conclusion Our IPD meta-analysis showed a small effect size of SSRIs in pediatric OCD, with baseline severity as a negative modifier of response. Generalizability of findings might be limited by selective inclusion of White, North American participants.