Individual patient data meta-analysis of placebo-controlled trials of selective serotonin reuptake inhibitors submitted for regulatory approval in adult obsessive-compulsive disorder

Br J Psychiatry. 2025 Oct;227(4):680-687. doi: 10.1192/bjp.2025.87. Epub 2025 May 15.

Abstract

Background: Selective serotonin reuptake inhibitors (SSRIs) are the preferred pharmacological treatment for obsessive-compulsive disorder (OCD). However, insufficient response is common and it remains unclear whether specific patient-level factors influence the likelihood of treatment response.

Aims: To determine the efficacy and acceptability of SSRIs in adult OCD, and to identify patient-level modifiers of efficacy.

Methods: We conducted an individual patient data meta-analysis (IPDMA) of industry-sponsored short-term, randomised, placebo-controlled SSRI trials submitted for approval to the Dutch regulatory agency to obtain marketing approval for treating OCD in adults. We performed a two-stage meta-analysis, using crude data of available trials. The primary outcome was the difference in Yale-Brown Obsessive-Compulsive Scale (YBOCS) change between active treatment and placebo. Secondary outcomes were differences in response (defined as the odds ratio of ≥35% YBOCS point reduction) and acceptability (defined as the odds ratio for all-cause discontinuation). We examined the modifying effect of baseline characteristics: age, gender, illness severity, depressive symptoms, weight, illness duration and history of antidepressant use.

Results: After excluding three trials because of missing data, we analysed results from 11 trials (79% of all submitted trials, n = 2372). The trial duration ranged from 10 to 13 weeks. Mean difference of SSRIs relative to placebo was 2.65 YBOCS points (95% CI 1.85-3.46, p < 0.0001), equalling a small effect size (0.33 Hedges' g). The odds ratio for response was 2.21 in favour of active treatment (95% CI 1.72-2.83, p < 0.0001), with a number needed to treat of seven. Patient characteristics did not modify symptom change or response. Acceptability was comparable for SSRIs and placebo.

Conclusions: Our IPDMA showed that SSRIs are well accepted and superior to placebo for treating OCD. The effects are modest and independent of baseline patient characteristics.

Keywords: Obsessive–compulsive disorders; individual patient data meta-analysis; pharmacotherapy; selective serotonin reuptake inhibitor.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Female
  • Humans
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder* / drug therapy
  • Randomized Controlled Trials as Topic
  • Selective Serotonin Reuptake Inhibitors* / therapeutic use

Substances

  • Selective Serotonin Reuptake Inhibitors