Enhancing Repetitive Transcranial Magnetic Stimulation Effects for Depression Treatment: Navigare Necesse Est—and Smart Clinical Trial Designs

Developments regarding technical aspects of repetitive Transcranial Magnetic Stimulation (rTMS) have been linked to better results in medication-resistant depression treatment. An intermittent theta-burst (iTBS) rTMS protocol optimized for these findings, namely the Stanford Neuromodulation Therapy, has in fact shown encouraging results in trials. Nonetheless, higher operational costs and reduced feasibility in average clinical settings may deter its applicability and overall reproducibility. Particularly, the need for personalized functional connectivity studies for neuronavigation guidance and greater logistic and patient-related requirements for conducting 10 daily sessions may be challenging. We report the results of an adapted accelerated iTBS protocol with fewer daily sessions and simpler target obtention method.Four patients in a severe, refractory depressive episode received five daily iTBS sessions (1800 pulses/session) spaced by 50 min, five days a week, for two weeks. Neuronavigated coil positioning used individualized neuroanatomic space but was targeted at a previously reported population-based left dorsolateral prefrontal–subgenual cingulate cortex peak anticorrelation coordinate (−38, 44, 26). Assessments were performed at baseline, at the end of 50 sessions and at two-week follow-up.At follow-up, three patients were responders and two had reached remission. Considering the whole sample, depression measures showed a 56.9% reduction, with a median decrease of 14.5 points on the PHQ-9.Uncontrolled study with a very small sample and short follow up time.The proposed intervention was feasible in a clinical practice setting, being well tolerated by patients and achieving a 3/4 response and 2/4 remission rates.