Abstract
Obsessive-compulsive disorder (OCD) and adolescent depression are debilitating conditions where standard treatments often yield suboptimal outcomes. Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique with established efficacy in adults with OCD, but its role in adolescent depression remains less defined. This systematic review aims to synthesize the current evidence on the efficacy, safety, and predictors of treatment response for TMS in adults with OCD and adolescents with depression. This review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A systematic search of PubMed/MEDLINE, Embase, PsycINFO, Web of Science, IEEE Xplore, and ClinicalTrials.gov was performed for studies published between 2020 and 2025. Eligible studies included randomized controlled trials (RCTs) and non-randomized interventional studies of TMS in adults with OCD or adolescents with depression. Data on efficacy, safety, and predictors of response were extracted. Risk of bias was assessed using the Cochrane RoB 2 and ROBINS-I tools. Nine studies were included (six on OCD and three on adolescent depression). For OCD, four of six RCTs reported significant reductions in Y-BOCS scores with active TMS compared to sham, targeting regions such as the dorsal anterior cingulate cortex (dACC), orbitofrontal cortex (OFC), and supplementary motor area (SMA). Protocols were highly heterogeneous, including accelerated theta-burst stimulation. For adolescent depression, one RCT combining repetitive TMS (rTMS) with fluoxetine in first-episode patients showed very high response rates compared to sham. Two open-label studies in treatment-resistant depression reported symptom reduction and correlated neural changes, though they lacked control groups. TMS was generally well-tolerated, with mostly mild adverse events; one serious event was reported. Neurocognitive testing showed no negative effects. The investigation of predictors of response was notably limited, with only preliminary evidence suggesting roles for neurocognitive performance, neural activation patterns, and symptom subtype. TMS demonstrates promise as an effective and safe intervention for both adults with OCD and adolescents with depression, though the evidence base is still evolving. Significant variability in protocols and a lack of long-term follow-up data exist. The most critical gap is the absence of robust predictors to guide personalized treatment selection. Future research should prioritize large, rigorous trials that focus on identifying biomarkers and clinical factors predictive of responses to optimize TMS therapy for these populations.