Within this landscape, treatment-resistant depression (TRD) represents a critical subset, affecting around 30% of patients with MDD. TRD is associated with elevated psychiatric and medical comorbidities, higher rates of suicide attempts, recurrent hospitalizations, and increased healthcare utilisation. Beyond clinical impairment, TRD imposes substantial emotional and economic burdens on families and caregivers, intensifying its societal impact.

Repetitive transcranial magnetic stimulation (rTMS) has emerged as a key alternative for treating TRD. Meta-analytic data show response rates of 29–46% and remission rates of 18–31%. However, challenges remain, including protocol heterogeneity, cost, and the fact that up to 40% of patients do not respond to standard TMS approaches. Current strategies to enhance effectiveness include increasing the number of sessions or pulses, exploring accelerated protocols, and shifting toward personalised TMS, particularly fMRI-guided and EEG-guided stimulation.

Recent advances such as the Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT) protocol have demonstrated rapid and high response rates in TRD, potentially surpassing traditional interventions. Looking ahead, the field is moving toward cost reduction and broader democratization of precision neuromodulation.