Trajectories of patient-rated baseline-severe depressive symptoms during repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder

Abstract Major Depressive Disorder (MDD) presents with heterogeneous symptom profiles. While repetitive Transcranial Magnetic Stimulation (rTMS) treatment is known to improve depressive symptoms overall, it remains unclear how rapidly individual symptoms that are rated as severe at baseline improve during a clinical course. We analyzed Inventory of Depressive Symptomatology Self-Rated (IDS-SR) data collected every five sessions during rTMS treatment of 741 patients with treatment-refractory depression (TRD). Symptoms were grouped into Somatic-Vegetative (S-V) or Affective-Cognitive (A-C) domains, and analyses were restricted to baseline-severe items (IDS-SR item score ≥2) on a within-patient basis to reduce floor effects. Linear mixed-effects models examined symptom trajectories across domains, and we quantified time to 50% sustained improvement for individual symptoms. S-V symptoms improved slightly faster than A-C symptoms early in treatment (sessions 5 and 10; p < 0.01), but differences between symptom domains were small in comparison to overall change over time and symptom domains converged by the end of treatment. Symptoms that improved earlier were more likely to achieve 50% sustained improvement throughout the course. These real-world data primarily inform expectation-setting: patients can anticipate generalized improvement across baseline-severe symptoms during a full rTMS course, with at most modest early differences between symptom domains.