Influence of study characteristics, methodological rigor and publication bias on efficacy of pharmacotherapy in obsessive compulsive disorder: a systematic review and meta-analysis of randomized placebo-controlled trials.

QuestionWe examined the effect of study characteristics, risk of bias and publication bias on efficacy of pharmacotherapy in randomized controlled trials (RCTs) for obsessive-compulsive disorder (OCD). Study selection and analysisWe conducted a systematic search for double-blinded, placebo controlled short-term RCTs with selective serotonergic reuptake inhibitors (SSRIs) or clomipramine. We performed a random-effect meta-analysis, using change of the Yale-Brown Obsessive-Compulsive scale (YBOCS) as primary outcome. We performed meta-regression for key study characteristics, and for risk of bias. Furthermore, we analyzed publication bias using a Bayesian selection model. FindingsWe screened 3729 articles and included 21 studies, containing 4102 participants. Meta-analysis showed an effect size of -0.59 (Hedges G, 95% CI -0.73 to -0.46), equaling 4.2 point reduction on the YBOCS compared to placebo. The most recent trial was performed in 2007 and most trials were at risk of bias. In our meta-regression, we found that high risk of bias was associated with a larger effect size. Clomipramine was more effective than SSRIs, even after correcting for risk of bias. We found an indication for publication bias subsequent correction for this bias resulted in a depleted effect size. ConclusionsOur findings reveal superiority of clomipramine over SSRIs, even after adjusting for risk of bias. Effect sizes may be attenuated when considering publication bias and methodological rigor, emphasizing the importance of robust studies to guide clinical utility of OCD pharmacotherapy.