Protocol of a single-arm open-label pilot study of extended rTMS therapy for treatment-resistant depression (ExTMS study).

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) has been covered by the Japanese public health insurance system. Standard public insurance-covered treatment is limited to a 30-session course delivered over 8 weeks. While rTMS therapy is effective for TRD, residual depressive symptoms frequently persist after treatment completion. This pilot study aims to prospectively evaluate whether extended rTMS therapy can further improve depressive symptoms and be safely administered in patients with TRD who have shown insufficient improvement after completion of the standard treatment course. METHODS: This is a 4-week single-arm open-label pilot study. Participants will be recruited from patients receiving standard public health insurance-covered rTMS therapy. Eligible participants are adults who achieved at least 20% improvement following the standard 30-session course but continue to experience residual depressive symptoms, defined as a 17-item Hamilton Depression Rating Scale (HAMD-17) total score of 5 or higher. Extended rTMS therapy will consist of 12 additional sessions administered over 4 weeks using the same stimulation protocol as the standard rTMS therapy. OUTCOMES: The primary outcome is the change in HAMD-17 total score from baseline, defined as completion of the standard 30-session course, to completion of extended treatment. Secondary outcomes include remission and minimal residual symptom rates, changes in depressive symptoms and patient-reported outcomes during treatment, and adverse events. CONCLUSIONS: This study will provide preliminary evidence regarding the potential clinical benefit of extended rTMS therapy for patients with residual depressive symptoms after completion of the standard treatment course.