Clinical predictors of treatment resistance to serotonin reuptake inhibitors in obsessive-compulsive disorder: a meta-analysis

Expert Rev Neurother. 2025 Dec 23:1-9. doi: 10.1080/14737175.2025.2605084. Online ahead of print.

Abstract

Background: Serotonin Reuptake Inhibitors (SRIs) are the first-line pharmacotherapy for obsessive-compulsive disorder (OCD), but they are effective in only 40-60% of the patients. We performed meta-analyses of predictors of resistance to SRIs in OCD.

Methods: The systematic review was conducted as per PRISMA guidelines and registered in PROSPERO (ID: CRD42024568797). Multiple random-effects meta-analyses were performed for each predictor, depending on the type of the predictor variable and the outcome (continuous vs categorical). Pooled outcomes were reported as odds ratios (OR), mean differences (MD), standardized mean differences (SMD), Fisher's r-to-z transformed correlation coefficient, along with their 95% confidence intervals (CI).

Results: Out of 10,688 studies screened, 46 met our eligibility criteria, including a total of N = 4860 subjects. Analysis of categorical outcomes showed that earlier age at onset (SMD = 1.9 [0.79-2.99]), longer duration of illness (SMD = 2.78 [0.77-4.79]), greater OCD severity at baseline (MD = 2.50 [1.53-3.46]), poorer insight (OR = 0.24 [0.08-0.68]), contamination obsessions (OR = 0.61 [0.43-0.85]), and comorbid tics (OR = 0.44 [0.29-0.67]) predicted non-response to SRIs. Baseline OCD severity (Z = 0.56 [0.21-0.92]), poorer insight (SMD = 1.33 [0.42-1.33]), and presence of comorbid tics (SMD = 0.67 [0.01-1.36]) predicted poor response in continuous outcome analyses.

Conclusions: Baseline severity, insight, and comorbid tics were consistent predictors of poor treatment response.

Keywords: Obsessive-compulsive disorder; meta-analysis; pharmacotherapy; predictors; serotonin reuptake inhibitors.

Publication types

  • Review