Systematic Review and Meta-Analysis: Early Treatment Responses of Selective Serotonin Reuptake Inhibitors and Clomipramine in Pediatric Obsessive-Compulsive Disorder

J Am Acad Child Adolesc Psychiatry. 2016 Oct;55(10):851-859.e2. doi: 10.1016/j.jaac.2016.07.768. Epub 2016 Aug 4.


Objective: We conducted a meta-analysis to examine the following: the time course of response to selective serotonin reuptake inhibitors (SSRIs) and clomipramine in pediatric obsessive-compulsive disorder (OCD); whether higher doses of SSRIs are associated with an improved response in pediatric OCD; differences in efficacy among SSRI agents; differences in efficacy between SSRIs and clomipramine; and whether the time course and magnitude of response to SSRIs are different in pediatric and adult patients with OCD.

Method: We searched PubMed and CENTRAL for randomized controlled trials comparing SSRIs (or clomipramine) to placebo for the treatment of pediatric OCD and using the Children's Yale-Brown Obsessive-Compulsive Scale as an outcome. 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 weighted mean differences between the treatment and placebo groups.

Results: Nine trials involving 801 children with OCD were included in this meta-analysis. A logarithmic model indicating that the greatest benefits occurred early in treatment best fit the longitudinal data for both clomipramine and SSRIs. Clomipramine was associated with a greater measured benefit compared to placebo than SSRIs. There was no evidence for a relationship between SSRI dosing and treatment effect, although data were limited. Adults and children with OCD demonstrated a similar degree and time course of response to SSRIs in OCD.

Conclusion: These results suggest that the greatest incremental treatment gains in pediatric OCD occur early in SSRI treatment (similar to adults with OCD and children and adults with major depression).

Keywords: clomipramine; meta-analysis; obsessive-compulsive disorder; selective serotonin reuptake inhibitors.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Child
  • Clomipramine / therapeutic use*
  • Humans
  • Obsessive-Compulsive Disorder / drug therapy*
  • Obsessive-Compulsive Disorder / psychology
  • Randomized Controlled Trials as Topic
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Treatment Outcome


  • Serotonin Uptake Inhibitors
  • Clomipramine