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

Abstract

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 not been investigated using individual participant data (IPD), which is crucial for detecting patient-level effect modifiers. This study performed an IPD meta-analysis of efficacy of SSRIs compared with placebo and a meta-regression on baseline patient characteristics that might modify efficacy.

Method: Crude participant data from short-term, randomized, placebo-controlled SSRI trials for pediatric OCD were obtained from the registry of the Dutch regulatory authority. A systematic literature search was also performed, and authors were approached to provide IPD. A 1- and 2-stage analysis was conducted, with change on Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) as the primary outcome. Odds ratio (OR) with ≥35% CY-BOCS reduction was used as the responder outcome measure. Modifying effect of age, sex, weight, duration of illness, family history, and baseline symptom severity was examined. The Cochrane RoB 2.0 tool was used to examine methodological rigor, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to examine certainty of evidence.

Results: Data were obtained from 4 studies comprising 614 patients. The sample represented 86% of all participants ever included in double-blind placebo-controlled SSRI trials for pediatric OCD. Meta-analysis showed reduction of 3.0 CY-BOCS points compared with placebo (95% CI 2.5-3.5), corresponding to a small effect size (0.38 Hedges' g). Analysis of response showed an odds ratio of 1.89 (95% CI 1.45-2.45). Of all possible modifiers, severity was correlated negatively with odds ratio for response (β = -0.92, p = .0074). Risk of bias was generally low. All studies were performed in North America with an overrepresentation of White participants. Findings were limited by inability to include data on additional variables such as socioeconomic status and comorbidities.

Conclusion: This 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.

Plain language summary: Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat children and adolescents with obsessive-compulsive disorder (OCD), but their effects have not been analyzed using individual participant data (IPD). Using data of 4 randomized, placebo-controlled trials comprising of 614 patients, this meta-analysis showed that SSRIs provided a modest improvement of 3 points on the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) compared to placebo. Children with more severe symptoms at baseline were less likely to respond. All studies were conducted in North America, with an overrepresentation of White participants. Children with more severe symptoms at baseline were less likely to respond well. These findings confirm the efficacy of SSRIs while underscoring the need for more diverse research populations to better understand their effects in pediatric OCD.

Study registration information: Patient Characteristics and Efficacy of SSRI Treatment in Children and Adolescents With Obsessive Compulsive Disorder: An Individual Participant Data Meta-analysis of Randomized, Placebo-Controlled Trials; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023486079.

Keywords: SSRIs; individual participant data meta-analysis; pediatric obsessive-compulsive disorder; randomized controlled trials.