Comparative efficacy of neuromodulation modalities for treatment-refractory obsessive-compulsive disorder: A systematic review, meta-analysis, and network-based analysis

Obsessive-compulsive disorder (OCD) is a severe psychiatric illness, with up to 40% of patients remaining refractory to standard treatments. Neuromodulation, including deep brain stimulation (DBS), lesion-based surgery, transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS), offers alternative strategies, though their comparative efficacy and network engagement remain uncertain. This meta-analysis of 143 studies involving 2,743 patients showed that the largest improvement effects were observed for lesion-based interventions (standardized mean difference (SMD) = 45.08) and DBS (SMD = 39.73), followed by tDCS (SMD = 28.77) and TMS (SMD = 26.56). Sham-controlled studies confirmed that active treatments outperformed placebo. Functional connectivity analysis of stimulated targets revealed network hubs (e.g., medial prefrontal cortex, anterior limb of the internal capsule, anterior cingulate cortex) as the most effective targets. These findings highlight neuromodulation as a viable therapeutic option and underscore the potential of connectivity-guided approaches in optimizing treatment outcomes.