Accelerated Multi-Target Theta-Burst Stimulation for Obsessive–Depressive–Anxious Symptoms: Real-World Outcomes of the aTTODA Protocol

Background: Obsessive–compulsive symptoms frequently co-occur with depression and anxiety, contributing to a complex and potentially treatment-resistant clinical phenotype. Although transcranial magnetic stimulation (TMS) is an established treatment option for obsessive–compulsive disorder (OCD), many patients continue to experience residual symptoms across multiple domains. Multi-target neuromodulation approaches may help address overlapping neural circuits. This study evaluated the real-world effectiveness and feasibility of an accelerated Triple-Target Obsessive–Depressive–Anxious (aTTODA) theta-burst stimulation protocol. Methods: In this naturalistic cohort study, 25 patients with treatment-resistant depressive–anxious disorder and comorbid OCD were treated with TMS at a specialized neuropsychiatric center. All patients received the accelerated aTTODA protocol, consisting of 30 sessions delivered over 3 weeks. Obsessive–compulsive, depressive, and anxiety symptoms were assessed at baseline and post-treatment using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), 17-item Hamilton Depression Rating Scale (HDRS-17), and Hamilton Anxiety Rating Scale (HAM-A), respectively. Results: Treatment with the aTTODA protocol was associated with significant improvements across all symptom domains (all p < 0.001), with large within-group effect sizes (Cohen’s d ≥1.0). Mean symptom reductions were 32.7% for the Y-BOCS, 44.6% for the HDRS-17, and 42.1% for the HAM-A. For OCD symptoms, 40% of patients met response criteria and 20% achieved remission. A shift toward lower Y-BOCS severity categories was also observed following treatment, suggesting broad clinical improvement beyond changes in mean symptom scores. Conclusions: In this complex, treatment-resistant population, the accelerated multi-target aTTODA protocol was associated with clinically meaningful improvements across obsessive–compulsive, depressive, and anxiety symptom domains. These preliminary findings support the feasibility of time-efficient, circuit-based neuromodulation strategies. However, controlled randomized, blinded, sham-controlled trials are needed to establish efficacy, durability of treatment effects, and optimal patient selection.