Advancing Repetitive Transcranial Magnetic Stimulation for Depression: Novel Protocols, Precision Targeting, and Future Directions

Major depressive disorder (MDD) remains a significant global health challenge, with substantial limitations inherent in current pharmacotherapeutic and psychotherapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a safe, effective, and non-invasive neuromodulation therapy, particularly for treatment-resistant depression (TRD). However, conventional rTMS is limited by long treatment duration and variable interindividual efficacy. This expert opinion examines recent advances in rTMS optimization strategies aimed at overcoming these limitations. Key areas of progress include the development of novel stimulation protocols such as theta-burst stimulation (TBS); accelerated regimens and priming TMS; the use of magnetic resonance imaging (MRI)-guided TMS; and the integration of closed-loop systems using real-time electroencephalography (EEG) or functional near-infrared spectroscopy (fNIRS) feedback. Additionally, technological innovations, including robot-assisted TMS and wearable devices, promise to enhance targeting accuracy and treatment accessibility. Despite these developments, significant challenges impede clinical translation, including the high cost of personalized protocols, insufficient standardization and validation of novel approaches, and technical barriers to closed-loop implementation. Future efforts should focus on cost reduction, large-scale randomized controlled trials, biomarker development, and device portability. Ultimately, optimized rTMS shows significant potential to become a more efficient, precise, and accessible cornerstone of depression therapy.