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

Abstract

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. To determine the efficacy and acceptability of SSRIs in adult OCD, and to identify patient-level modifiers of efficacy. 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. After excluding three trials because of missing data, we analysed results from 11 trials (79% of all submitted trials, <i>n</i> = 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, <i>p</i> < 0.0001), equalling a small effect size (0.33 Hedges' <i>g</i>). The odds ratio for response was 2.21 in favour of active treatment (95% CI 1.72-2.83, <i>p</i> < 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. 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.