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JAMA Psychiatry. 2018 Sep 1;75(9):884-893. doi: 10.1001/jamapsychiatry.2018.1483.

Effect of Repetitive Transcranial Magnetic Stimulation on Treatment-Resistant Major Depression in US Veterans: A Randomized Clinical Trial.

Author information

Department of Veterans Affairs, Sierra-Pacific Mental Illness Research Educational and Clinical Center, Palo Alto, California.
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.
Department of Veterans Affairs, Cooperative Studies Program Coordinating Center, Perry Point, Maryland.
Department of Veterans Affairs, Cooperative Studies Program Pharmacy Coordinating Center, Albuquerque, New Mexico.
Department of Veterans Affairs, Health Economics Resource Center and Center for Implementation to Innovation, Palo Alto, California.
Department of Pediatrics, Stanford University School of Medicine, Stanford, California.
Department of Veterans Affairs, Veterans Affairs Medical Center, Pittsburgh, Pennsylvania.
Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Department of Veterans Affairs, Veterans Affairs Medical Center, Philadelphia, Pennsylvania.
Stanford Neurosciences Institute, Stanford University, Stanford, California.
Department of Veterans Affairs, Cooperative Studies Program Central Office, Washington, DC.
Department of Veterans Affairs, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina.
Brain Stimulation Laboratory, Psychiatry Department, Medical University of South Carolina, Charleston.



Treatment-resistant major depression (TRMD) in veterans is a major clinical challenge given the high risk for suicidality in these patients. Repetitive transcranial magnetic stimulation (rTMS) offers the potential for a novel treatment modality for these veterans.


To determine the efficacy of rTMS in the treatment of TRMD in veterans.

Design, Setting, and Participants:

A double-blind, sham-controlled randomized clinical trial was conducted from September 1, 2012, to December 31, 2016, in 9 Veterans Affairs medical centers. A total of 164 veterans with TRD participated.


Participants were randomized to either left prefrontal rTMS treatment (10 Hz, 120% motor threshold, 4000 pulses/session) or to sham (control) rTMS treatment for up to 30 treatment sessions.

Main Outcomes and Measures:

The primary dependent measure of the intention-to-treat analysis was remission rate (Hamilton Rating Scale for Depression score ā‰¤10, indicating that depression is in remission and not a clinically significant burden), and secondary analyses were conducted on other indices of posttraumatic stress disorder, depression, hopelessness, suicidality, and quality of life.


The 164 participants had a mean (SD) age of 55.2 (12.4) years, 132 (80.5%) were men, and 126 (76.8%) were of white race. Of these, 81 were randomized to receive active rTMS and 83 to receive sham. For the primary analysis of remission, there was no significant effect of treatment (odds ratio, 1.16; 95% CI, 0.59-2.26; Pā€‰=ā€‰.67). At the end of the acute treatment phase, 33 of 81 (40.7%) of those in the active treatment group achieved remission of depressive symptoms compared with 31 of 83 (37.4%) of those in the sham treatment group. Overall, 64 of 164 (39.0%) of the participants achieved remission.

Conclusions and Relevance:

A total of 39.0% of the veterans who participated in this trial experienced clinically significant improvement resulting in remission of depressive symptoms; however, there was no evidence of difference in remission rates between the active and sham treatments. These findings may reflect the importance of close clinical surveillance, rigorous monitoring of concomitant medication, and regular interaction with clinic staff in bringing about significant improvement in this treatment-resistant population.

Trial Registration: Identifier: NCT01191333.

[Indexed for MEDLINE]
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