Optimizing non-invasive brain stimulation for obsessive-compulsive disorder: a systematic review of protocol heterogeneity, personalized targets, and adjunctive efficacy

Obsessive-Compulsive Disorder (OCD) is a chronic psychiatric disorder characterized by intrusive thoughts and repetitive behaviors, leading to significant distress and functional impairment. First-line treatments include selective serotonin reuptake inhibitors and cognitive-behavioral therapy, particularly exposure and response prevention (ERP). However, a substantial proportion of patients exhibit limited or no response to these interventions. Repetitive transcranial magnetic stimulation (rTMS) has shown potential in modulating dysfunctional cortical circuits implicated in OCD pathophysiology. Notably, the field achieved a major clinical milestone with the U.S. Food and Drug Administration (FDA) clearance in 2018 for Deep TMS (dTMS) targeting the medial prefrontal cortex (mPFC) and anterior cingulate cortex using the H7 coil, based primarily on positive randomized controlled trials. Despite promising findings, clinical studies on rTMS report heterogeneous outcomes, possibly due to variations in stimulation parameters, target regions, and study designs. These inconsistencies underscore the need for a comprehensive synthesis of current evidence. A comprehensive literature search was conducted across PubMed, ScienceDirect, and Scopus up to August 15, 2025. Eligible studies included adult OCD patients receiving multi-session rTMS protocols. Non-RCT, case reports, non-English studies, and non-primary literature were excluded. Risk of Bias Tool (RoB v1) was assessed using the Cochrane Collaboration tool. Forty-seven studies involving 1,632 participants were included. The most frequently targeted regions were the supplementary motor area (SMA) and dorsolateral prefrontal cortex (dlPFC). Low-frequency (1 Hz) stimulation was the most commonly applied protocol. While several studies demonstrated significant improvement in some of OCD symptoms, other studies reported minimal or no benefit. Methodological heterogeneity, particularly in stimulation parameters and target selection, precludes definitive conclusions. Notably, studies combining rTMS with pharmacological or psychotherapeutic interventions and those incorporating neurobiological predictors such as neuroimaging or genetic polymorphisms suggest potential for enhanced outcomes through personalized treatment strategies. Current evidence supports rTMS as a potentially effective adjunctive treatment for OCD, particularly when targeting the SMA and dlPFC. However, variability in methodological quality and treatment parameters underscores the need for standardized protocols and high-quality RCTs. Integrating neurobiological predictors and combining rTMS with established therapies may optimize treatment efficacy in future investigations.