Effectiveness of Deep Brain Stimulation for Treatment-Resistant OCD: Systematic Review of Anatomical Targets and Meta-Analysis of Randomized and Non-Randomized Studies.

BACKGROUND: Deep brain stimulation (DBS) is a promising intervention for severe treatment-resistant OCD (TR-OCD), yet evidence of clinical efficacy remains inconsistent across heterogeneous study designs and anatomical target selection lacks standardization. Whether target choice influences clinical outcomes has not been systematically established, and prior meta-analyses have not characterized target-specific effects or predictors of response. OBJECTIVES: This systematic review and meta-analysis evaluated the efficacy of DBS versus sham stimulation in RCTs and its effectiveness in non-randomized studies, with OCD symptom severity, comorbid anxiety and depression, and global functioning as outcomes. Secondary objectives were to examine whether anatomical stimulation site influences therapeutic outcomes using systematic recategorization of reported targets, and to characterize the temporal dynamics of treatment response. METHODS: Four databases (PubMed, Embase, Web of Science, CENTRAL) were searched through July 2025 following PRISMA 2020 guidelines. RCTs (active vs. sham DBS) and non-randomized studies reporting pre/post-DBS Y-BOCS scores were analyzed separately at three time points (≤12 months, >12 months, last follow-up). Stimulation targets were recategorized using active contact location and stereotactic coordinates. Random-effects models, meta-regression, RoB 2, ROBINS-I, and GRADE were applied. RESULTS: Eight RCTs (n = 83) and 32 non-randomized studies (n = 321) were included. In RCTs, active DBS reduced Y-BOCS scores by 6.92 points (95% CI: 4.46-9.38; 18.3%; p < 0.001; I2 = 62.93%) versus sham. Non-randomized studies demonstrated reductions of 13.83 points (95% CI: 11.01-16.52), 17.34 points (95% CI: 14.70-20.04), and 14.51 points (95% CI: 12.78-16.26; 43.5%; p < 0.001) at ≤12 months, >12 months, and last follow-up, respectively, with substantial heterogeneity (I2 ≥ 89.79%). Responder and remission rates were 60.2% (95% CI: 52.8-67.2%; I2 = 20.7%) and 36.4% (95% CI: 29.8-43.5%; I2 = 12.1%), respectively. Anxiety (k = 7; d = 1.1; 95% CI: 0.72-1.56), depression (k = 24; d = 1.1; 95% CI: 0.80-1.26), and global functioning (k = 14; baseline GAF = 34.5; MD = 25.62; 95% CI: 22.18-29.03) improved significantly (all p < 0.001). In meta-regression, longer follow-up duration was the only significant predictor of Y-BOCS improvement (p = 0.042). Therapeutic effects varied substantially across anatomical stimulation sites. The anterior limb of the internal capsule (ALIC) and its ventral subdivision (vALIC) were most frequently stimulated. The inferior thalamic peduncle was associated with the largest mean Y-BOCS improvement (19.70 points; based on two trial arms only), nucleus accumbens stimulation did not reach the clinical response threshold (≥35% Y-BOCS reduction), and mediodorsal/ventral anterior thalamic stimulation showed no statistically significant benefit. Sensitivity analyses confirmed the robustness of primary estimates. Evidence quality was moderate (RCTs) and low (non-randomized studies). CONCLUSIONS: DBS significantly reduces OCD symptom severity in TR-OCD despite substantial heterogeneity, with greater improvements associated with longer follow-up duration and effects maintained for at least 30 months, alongside improvements in comorbid anxiety, depression, and global functioning. Not all anatomical stimulation sites are therapeutically equivalent, underscoring the importance of target selection. High-quality RCTs with standardized anatomical reporting are needed to consolidate the evidence base.