The severity of treatment-resistant depression and the response to repetitive transcranial magnetic stimulation: a prospective, observational, multi-center clinical cohort study

Background The Maudsley Staging Method (MSM) is a multidimensional framework for grading treatment resistance in depression (TRD); however, its ability to predict clinical response to repetitive transcranial magnetic stimulation (rTMS) remains unclear.Objective To examine the association between MSM-graded treatment resistance and clinical response during rTMS.To investigate links between MSM scores, longitudinal changes in patient-reported depressive symptoms, and mental well-being.Methods Prospective observational study including patients with unipolar depression referred to a six-week course of rTMS in routine psychiatric care. MSM was assessed within the first two weeks. Patients were stratified into mild (<7), and moderate/severe MSM groups (≥7). Weekly assessments comprised: Clinician-rated (17-item Hamilton Depression Rating Scale (HAM-D17)), patient-reported depressive symptoms, and mental well-being questionnaires. Response was defined as ≥50% decrease or remission using HAM-D17 score. Data were examined using linear mixed-effects models and multivariable logistic regression.Results Of 67 patients (61% female, mean age: 46 ± 16 years), 21% achieved a response and 17% achieved remission. MSM scores were inversely correlated with treatment response (odds ratio: 0.49, p = 0.008). HAM-D17 scores declined significantly by week 5 in the mild MSM group (30.0%), and by week 3 in the moderate/severe MSM group (21.6%). By week 6, the mild MSM group showed the greatest improvement (mean decrease: HAM-D17: 5.1 vs. 4.6 points, p = 0.030).Conclusions Baseline MSM-graded TRD was associated with differential response patterns to rTMS, characterized by earlier symptom improvement in the moderate/severe MSM group but greater overall symptom reduction in the mild group.