Obsessive-compulsive disorder (OCD), characterized by distressing obsessions and compulsions, affects 2.5–3% of the population. Current first-line treatments, including cognitive-behavioral therapy and selective serotonin reuptake inhibitors, are ineffective for a significant portion of patients. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, offers a potential alternative. rTMS modulates brain activity by passing a magnetic field through the scalp, targeting neural circuits implicated in OCD, such as the cortico-striato-thalamo-cortical (CSTC) loop. Different stimulation frequencies (low-frequency, inhibiting; high-frequency, excitatory) impact brain activity differently. The optimal rTMS parameters (target brain region, stimulation frequency) for OCD treatment remain unclear, with various strategies employed, including LF/HF rTMS over the left dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), or anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC). This study aimed to compare the efficacy and tolerability of these different rTMS strategies.

The introduction section reviews the existing literature on OCD treatment, highlighting the limitations of current first-line treatments and the rationale for exploring rTMS as an alternative. It explains the mechanism of rTMS and its potential to modulate the neural circuits involved in OCD. The review notes the lack of consensus on the most effective rTMS parameters for OCD, setting the stage for the systematic review and meta-analysis.

This study conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) investigating rTMS for OCD treatment. Five electronic databases were searched (Cochrane Central Register of Controlled Trials, PubMed, Web of Science, Embase, PsycInfo) from inception to March 25, 2020. Included studies were RCTs with parallel or crossover designs in adults (≥18 years) diagnosed with OCD using established criteria (Research Diagnostic Criteria, DSM, or ICD). The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to assess symptom severity. Data extracted included subject characteristics, rTMS parameters (location, frequency), treatment characteristics (number of sessions, duration), and Y-BOCS scores. Pairwise meta-analyses assessed direct comparisons within a random-effects model, calculating mean differences (MD) in Y-BOCS score changes and odds ratios (OR) of dropout rates. Network meta-analyses, using a Bayesian framework, assessed both direct and indirect comparisons. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to assess the quality of evidence. Sensitivity analyses were conducted to assess the impact of potential biases and effect modifiers. Risk of bias was assessed using the Cochrane risk of bias tool.

Twenty-two RCTs (698 participants) were included. Pairwise meta-analysis showed that LF-rTMS over the DLPFC and HF-rTMS over the DLPFC were significantly more effective than sham rTMS in reducing Y-BOCS scores. Network meta-analysis confirmed these findings, with LF-rTMS over the DLPFC and SMA ranking highest in efficacy. No significant differences in dropout rates (tolerability) were found among the rTMS strategies. High heterogeneity was observed for efficacy, potentially due to factors such as age, sex, treatment resistance, and target location (left vs. right brain). Sensitivity analyses did not materially alter the primary results. The quality of evidence for efficacy was rated as very low.

The findings suggest that LF-rTMS over the DLPFC may be a promising treatment for OCD, although the very low quality of evidence necessitates caution. The high heterogeneity observed highlights the need for more robust and homogenous studies. Subgroup analyses revealed potential effect modifiers such as age, sex, treatment resistance, and target brain region, suggesting that individual patient characteristics may influence treatment response. Future research should focus on high-quality RCTs with standardized methodologies and larger sample sizes to clarify the optimal rTMS parameters for OCD treatment and identify patient subgroups most likely to benefit.

This meta-analysis suggests a potential benefit of LF-rTMS over the DLPFC for OCD, but the low quality of evidence limits the strength of this conclusion. Future research with rigorous methodology and larger samples is crucial to confirm these findings and guide clinical practice. Further investigation into potential effect modifiers identified in subgroup analyses could lead to personalized treatment approaches.

The study's limitations include the very low quality of evidence for efficacy, high heterogeneity across studies, and the potential influence of publication bias. The limited number of studies evaluating specific rTMS parameters also restricts the generalizability of the findings. The reliance on existing literature, with its inherent variability in methodology and reporting, might have influenced the results.