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. 2025 Nov-Dec;18(6):1887-1895.
doi: 10.1016/j.brs.2025.10.005. Epub 2025 Oct 9.

The trajectory of symptom change over the course of transcranial magnetic stimulation for major depressive disorder

Linda L Carpenter  1 , Scott T Aaronson  2 , Todd Hutton  3 , Kenneth Pages  4 , A John Rush  5 , Harold A Sackeim  6
Affiliations
Free article

The trajectory of symptom change over the course of transcranial magnetic stimulation for major depressive disorder

Linda L Carpenter et al. Brain Stimul. 2025 Nov-Dec.
Free article

Abstract

Background: The trajectory of improvement in depression severity during TMS needs specification and the trajectories of individual symptoms are largely unexplored.

Methods: PHQ-9 and QIDS-SR data were analyzed from 402 patients with MDD who received ≥36 TMS sessions and scored ≥10 on both instruments at baseline. Total severity and individual symptoms were assessed at baseline, after 5, 10, 20, and 30 sessions, and at the end-of-acute treatment. The extent to which TMS produced generalized improvement across symptoms or symptom-specific trajectories was evaluated.

Results: The findings were consistent across the PHQ-9 and QIDS-SR. The average trajectory in total scores reflected rapid improvement from baseline to the 5th session. The rate of improvement per session was markedly slower, but consistent, thereafter. Across 6 time points, the 9 symptom domains differed markedly in severity (ηP2=31-37 %). Similarly, there were large effects of time point across symptoms, reflecting generalized and progressive therapeutic change (ηP2=44-48 %). While statistically significant, only a small portion of the variance was due to differences among the items in their change over time (ηP2=2-3 %). TMS protocols and groups differing in clinical outcome did not differ in type or extent of symptom specificity. At the group level, the predominant pattern was a marked and progressive downward shift of the baseline profile of symptom severity throughout the course of TMS.

Limitations: The findings derived from two self-report instruments.

Conclusions: The trajectory of the antidepressant effect of TMS is nonlinear and generalized across depressive symptoms, showing limited symptom specificity.

Keywords: Major depressive disorder; PHQ-9; QIDS-SR; Symptom profile; Transcranial magnetic stimulation.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Dr. Carpenter serves as a scientific advisor to, or received consulting income from, Neuronetics Inc, Nexstim PLC, Affect Neuro Inc, Neurolief LTD, Sage Therapeutics, Otsuka, Magnus Medical Inc, MAPS Public Benefit Corp, and Janssen Pharmaceuticals Inc. Dr. Carpenter has received research support (to Butler Hospital) from Neuronetics Inc, Neosync Inc, Nexstim PLC, Affect Neuro Inc, Neurolief, Gray Matters Health and Janssen Pharmaceuticals Inc.Dr. Aaronson serves as a scientific adviser to Compass Pathways, Genomind Inc, LivaNova PLC, Neuronetics Inc, and Sage Therapeutics and has received research support from Compass Pathways Inc.Drs. Hutton and Pages serve as consultants to Neuronetics Inc.Dr. Rush has received consulting fees from Compass, Curbstone Consultant, Emmes, Evecxia Therapeutics, Holmusk Technologies, ICON, Johnson and Johnson (Janssen), LivaNova, MindStreet, Neurocrine Biosciences, Otsuka-US; speaking fees from LivaNova, Johnson and Johnson (Janssen), and Wolters Kluwer Health; royalties from Guilford Press and UT Southwestern Medical Center (for the Inventory of Depressive Symptoms and its derivatives); named co-inventor on US Patent 7,795,033 (Methods to Predict the Outcome of Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S, Wilson AS) and US Patent 7,906,283 (Methods to Identify Patients at Risk of Developing Adverse Events During Treatment with Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S).Dr. Sackeim serves as a scientific adviser to and receives consulting fees from Cerebral Therapeutics Inc, Holmusk Inc, LivaNova PLC, MECTA Corporation, NeuroInsights Inc., Neurolief LTD, Neuronetics Inc, Parow Entheobiosciences LLC and SigmaStim LLC. He receives honoraria and royalties from Elsevier Inc and Oxford University Press. He is the inventor on non-remunerative US patents for Focal Electrically-Administered Seizure Therapy (FEAST), titration in the current domain in ECT, and the adjustment of current in ECT devices, each held by SigmaStim LLC. He is also the originator of magnetic seizure therapy (MST).Therapeutics Inc, Holmusk Inc, LivaNova PLC, MECTA Corporation, NeuroInsights Inc., Neurolief LTD, Neuronetics Inc, Parow Entheobiosciences LLC and SigmaStim LLC. He receives honoraria and royalties from Elsevier Inc and Oxford University Press. He is the inventor on non-remunerative US patents for Focal Electrically-Administered Seizure Therapy (FEAST), titration in the current domain in ECT, and the adjustment of current in ECT devices, each held by SigmaStim LLC. He is also the originator of magnetic seizure therapy (MST).

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